[Continuous Optimisation of Experimental Models - an Example from Glaucoma Research]. / Die kontinuierliche Optimierung von experimentellen Modellen ­ Darstellung an einem Beispiel aus der Glaukomforschung.

BACKGROUND: There is a great demand for suitable models to test novel surgical and therapeutic approaches in glaucoma therapy. To address this need and to provide further alternatives to in vivo animal models, we aimed at modifying an established in vitro porcine eye perfusion model. METHODS: Two weaknesses of the previously established porcine anterior segment model include media leakage during perfusion and setup disintegration due to mechanical instability. To overcome these, we slightly modified the previously used custom-made perfusion dishes and incorporated new components into the model setup. To prevent fluid leakage, we secured the anterior segments more firmly to the perfusion trays using a compression ring, steel screws, and nuts. Customised mounts were used to stabilise the perfusion dish and pressure transducer as a single unit. The mounts were made of polylactide (PLA) and printed using a 3D printer. RESULTS: The use of steel screws and nuts allowed tighter clamping of the anterior segments and prevented medium leakage. Our PLA custom mounts stabilised the entire assembly and facilitated handling during experiments and improved comparability between tested eyes. They also prevented accidental detachment of the pressure transducers, which resulted in more stable pressure curves. Our PLA mounts tolerated incubation temperatures of up to 37 °C and disinfection with enzymatic detergents and 70% ethanol without showing signs of deformation or degradation after four months of regular usage. CONCLUSION: Modifications introduced to an established in vitro perfusion model improved its efficacy and reproducibility. Our adjusted model is an example of how many models can be optimised through critical analysis, thereby saving resources and providing reliable results in the long run.

VEGF-A-induced changes in distal outflow tract structure and function.

PURPOSE: To investigate changes in distal outflow tract vessels caused by VEGF-A and their impact on outflow. METHODS: We compared VEGF-A perfused porcine anterior segments with and without trabecular meshwork (TM) to control eyes. In the first experiment (n=48), we analyzed live changes of the outflow tract with spectral-domain optical coherence tomography (SD-OCT) over 3 h and reconstructed them in 3D. In a second experiment (n=32), we measured the intraocular pressure (IOP) variation in response to VEGF-A over 48 h and computed the outflow facility. RESULTS: VEGF-A increased the vessel volume of the distal outflow tract by 16.8±10.6% while control eyes remained unchanged (0.5±6.8%). Volume changes occurred within the first 100 min before plateauing at 140 min. VEGF-A enhanced the outflow facility in eyes without TM by 38.6±25.5% at 24 h as compared to controls (p<0.05). CONCLUSION: VEGF-A dilated vessels of the distal outflow tract and increased the outflow facility even after TM removal, pointing to a regulatory mechanism independent of proximal structures.

Coarsened Exact Matching of Excisional to Plasma-ablative Ab Interno Trabeculectomy.

Aim: To compare ab interno trabeculectomy by trabecular meshwork (TM) excision to plasma-mediated ablation in primary open-angle glaucoma (POAG) patients. Methods: Retrospectively collected data of TrabEx+ (TEx) (n = 56) and Trabectome (T) (n = 99) patients were compared by coarsened exact matching to reduce confounding and matched based on baseline intraocular pressure (IOP) and age. The primary outcomes were IOP and the number of glaucoma medications. Complications and the need for additional glaucoma surgery were assessed. Patients were followed for up to 1 year. Results: A total of 53 TEx could be matched to T. Baseline IOP was 16.5 ± 4.6 mm Hg in both; age was 73.7 ± 8.8 and 71.5 ± 9.9 years in TEx and T, respectively. TEx was taking more medications than T (p < 0.001). IOP was reduced to 14.8 ± 4.3 in TEx and to 13.4 ± 3.4 in T at 6 months, and to 14.9 ± 6.0 (p = 0.13) in TEx and to 14.1 ± 3.8 mm Hg (all p < 0.05) in T at 12 months. Medications were reduced at both 6 and 12 months (p < 0.05). No differences were seen between TEx and T at 6 and 12 months. In TEx, only one serious complication occurred, and two patients required further glaucoma surgery. Conclusion: Although both groups had a baseline IOP considered low for ab interno trabeculectomy, IOP and medications were reduced further at 6 and 12 months. IOP reduction did not reach significance in TEx at 12 months. The intergroup comparison did not reveal any significant differences. Both had a low complication rate. Clinical significance: This study investigated subtle differences between a plasma-ablative device, the T, and an excisional device, the TEx, by applying coarsened exact matching. IOP and medications were reduced in both groups at 6 and 12 months, although IOP reduction did not reach significance in TEx at 12 months. The intergroup comparison did not reveal any significant differences, with both devices having a low complication rate. How to cite this article: Dakroub M, Verma-Fuehring R, Strzalkowska A, et al. Coarsened Exact Matching of Excisional to Plasma-ablative Ab Interno Trabeculectomy. J Curr Glaucoma Pract 2023;17(1):9-14.

Tissue-engineered anterior segment eye cultures demonstrate hallmarks of conventional organ culture.

BACKGROUND: Glaucoma is a blinding disease largely caused by dysregulation of outflow through the trabecular meshwork (TM), resulting in elevated intraocular pressure (IOP). We hypothesized that transplanting TM cells into a decellularized, tissue-engineered anterior segment eye culture could restore the outflow structure and function. METHODS: Porcine eyes were decellularized with freeze-thaw cycles and perfusion of surfactant. We seeded control scaffolds with CrFK cells transduced with lentiviral vectors to stably express eGFP and compared them to scaffolds seeded with primary TM cells as well as to normal, unaltered eyes. We tracked the repopulation behavior, performed IOP maintenance challenges, and analyzed the histology. RESULTS: Transplanted cells localized to the TM and progressively infiltrated the extracellular matrix, reaching a distribution comparable to normal, unaltered eyes. After a perfusion rate challenge to mimic a glaucomatous pressure elevation, transplanted and normal eyes reestablished a normal intraocular pressure (transplanted = 16.5 ± 0.9 mmHg, normal = 16.9 ± 0.9). However, eyes reseeded with eGFP-expressing CrFK cells could not regulate IOP, remaining high and unstable (27.0 ± 6.2 mmHg) instead. CONCLUSION: Tissue-engineered anterior segment scaffolds can serve as readily available, scalable ocular perfusion cultures. This could reduce dependency on scarce donor globes in outflow research and may allow engineering perfusion cultures with specific geno- and phenotypes.

HIOP-Reader: Automated Data Extraction for the Analysis of Manually Recorded Nycthemeral IOPs and Glaucoma Progression.

Purpose: Nycthemeral (24-hour) intraocular pressure (IOP) monitoring in glaucoma has been used in Europe for more than 100 years to detect peaks missed during regular office hours. Data supporting this practice are lacking, because it is difficult to correlate manually drawn IOP curves to objective glaucoma progression. To address this, we developed an automated IOP data extraction tool, HIOP-Reader. Methods: Machine learning image analysis software extracted IOP data from hand-drawn, nycthemeral IOP curves of 225 retrospectively identified patients with glaucoma. The relationship between demographic parameters, IOP, and mean ocular perfusion pressure (MOPP) data to spectral-domain optical coherence tomography (SDOCT) data was analyzed. Sensitivities and specificities for the historical cutoff values of 15 mm Hg and 22 mm Hg in detecting glaucoma progression were calculated. Results: Machine data extraction was 119 times faster than manual data extraction. The IOP average was 15.2 ± 4.0 mm Hg, nycthemeral IOP variation was 6.9 ± 4.2 mm Hg, and MOPP was 59.1 ± 8.9 mm Hg. Peak IOP occurred at 10 am and trough at 9 pm. Progression occurred mainly in the temporal-superior and temporal-inferior SDOCT sectors. No correlation could be established between demographic, IOP, or MOPP variables and disease progression on OCT. The sensitivity and specificity of both cutoff points (15 and 22 mm Hg) were insufficient to be clinically useful. Outpatient IOPs were noninferior to nycthemeral IOPs. Conclusions: IOP data obtained during a single visit make for a poor diagnostic tool, no matter whether obtained using nycthemeral measurements or during outpatient hours. Translational Relevance: HIOP-Reader rapidly extracts manually recorded IOP data to allow critical analysis of existing databases.

Inter-eye correlation analysis of 24-h IOPs and glaucoma progression.

PURPOSE: To determine whether 24-h IOP monitoring can be a predictor for glaucoma progression and to analyze the inter-eye relationship of IOP, perfusion, and progression parameters. METHODS: We extracted data from manually drawn IOP curves with HIOP-Reader, a software suite we developed. The relationship between measured IOPs and mean ocular perfusion pressures (MOPP) to retinal nerve fiber layer (RNFL) thickness was analyzed. We determined the ROC curves for peak IOP (Tmax), average IOP(Tavg), IOP variation (IOPvar), and historical IOP cut-off levels to detect glaucoma progression (rate of RNFL loss). Bivariate analysis was also conducted to check for various inter-eye relationships. RESULTS: Two hundred seventeen eyes were included. The average IOP was 14.8 ± 3.5 mmHg, with a 24-h variation of 5.2 ± 2.9 mmHg. A total of 52% of eyes with RNFL progression data showed disease progression. There was no significant difference in Tmax, Tavg, and IOPvar between progressors and non-progressors (all p > 0.05). Except for Tavg and the temporal RNFL, there was no correlation between disease progression in any quadrant and Tmax, Tavg, and IOPvar. Twenty-four-hour and outpatient IOP variables had poor sensitivities and specificities in detecting disease progression. The correlation of inter-eye parameters was moderate; correlation with disease progression was weak. CONCLUSION: In line with our previous study, IOP data obtained during a single visit (outpatient or inpatient monitoring) make for a poor diagnostic tool, no matter the method deployed. Glaucoma progression and perfusion pressure in left and right eyes correlated weakly to moderately with each other.

Association between conventional or blue-light-filtering intraocular lenses and survival in bilateral cataract surgery patients.

Circadian rhythms regulate adaptive alterations in mammalian physiology and are maximally entrained by the short wavelength blue spectrum; cataracts block the transmission of light, particularly blue light. Cataract surgery is performed with two types of intraocular lenses (IOL): (1) conventional IOL that transmit the entire visible spectrum and (2) blue-light-filtering (BF) IOL that block the short wavelength blue spectrum. We hypothesized that the transmission properties of IOL are associated with long-term survival. This retrospective cohort study of a 15-hospital healthcare system identified 9,108 participants who underwent bilateral cataract surgery; 3,087 were implanted with conventional IOL and 6,021 received BF-IOL. Multivariable Cox proportional hazards models that included several a priori determined subgroup and sensitivity analyses yielded estimates supporting that conventional IOL compared with BF-IOL may be associated with significantly reduced risk of long-term death. Confirming these differences and identifying any potential causal mechanisms await the conduct of appropriately controlled prospective translational trials.

Exact matching of trabectome-mediated ab interno trabeculectomy to conventional trabeculectomy with mitomycin C followed for 2 years.

PURPOSE: We used exact matching for a highly balanced comparison of ab interno trabeculectomy (AIT) with the trabectome to trabeculectomy with mitomycin C (TRAB). METHODS: A total of 5485 patients who underwent AIT were exact-matched to 196 TRAB patients by baseline intraocular pressure (IOP), number of glaucoma medications, and glaucoma type. Nearest-neighbor-matching was applied to age. Success was defined as a final IOP of less than 21 mmHg, IOP reduction of at least 20% reduction from baseline, and no secondary surgical interventions. Outcomes were measured at 1, 3, 6, 12, 18, and 24 months. RESULTS: A total of 165 AIT could be matched to 165 TRAB. The mean baseline IOP was 22.3 ± 5.6 mmHg, and the baseline number of glaucoma medications was 2.7 ± 1.1 in both groups. At 24 months, IOP was reduced to 15.8 ± 5.2 mmHg in AIT and 12.4 ± 4.7 mmHg in TRAB. IOP was lower than baseline at all visits (p < 0.01) and lower in TRAB than AIT (p < 0.01). Glaucoma medications were reduced to 2.1 ± 1.3 in AIT and 0.2 ± 0.8 in TRAB. Compared to baseline, patients used fewer drops postoperatively (p < 0.01) and more infrequently in TRAB than in AIT (p > 0.01). Secondary surgical interventions had the highest impact on success and became necessary in 15 AIT and 59 TRAB patients. Thirty-two challenging events occurred in TRAB and none in AIT. CONCLUSION: Both AIT and TRAB reduced IOP and medications. This reduction was more significant in TRAB but at the expense of four times as many secondary interventions.

Combining Baerveldt Implant with Trabectome Negates Tube Fenestration: A Coarsened-matched Comparison.

PURPOSE: To assess the efficacy and survival rate of the Trabectome-mediated ab interno trabeculectomy combined with non-fenestrated Baerveldt glaucoma implant compared with the Baerveldt glaucoma implant alone. METHODS: In this retrospective comparative case series, 175 eyes undergoing primary glaucoma surgery (Baerveldt-Trabectome [BT] group: 60 eyes and Baerveldt [B] group: 115 eyes) were included. Participants were identified using the procedural terminology codes. Groups were then matched by Coarsened Exact Matching that resulted in the inclusion of 51 eyes in each group. The primary outcome measure was surgical success defined as 5 mmHg < intraocular pressure (IOP) ≤ 21 mmHg, and IOP reduction ≥ 20% from baseline, and no need to reoperation for glaucoma. Secondary outcome measures were IOP, number of glaucoma medications, and best-corrected visual acuity (BCVA). RESULTS: The cumulative probability of success at one year was 61% in the BT group and 50% in the B group. IOP decreased from 23.5 ± 2.4 mmHg at baseline to 14.1 ± 2.7 mmHg at the final follow-up in the BT group (P = 0.001). The corresponding values for the B group were 23.2 ± 2.0 mmHg and 13.9 ± 1.6 mmHg, respectively (P = 0.001). There was no significant difference between the groups in terms of IOP at the final follow-up (P = 0.56). The number of medications at baseline was 2.3 ± 0.3 in both groups. However, the BT group needed fewer drops at all postoperative time intervals and used 1.1 ± 0.3 versus 2.0 ± 0.4 eye drops (group B) at the final follow-up visit (P = 0.004). Eyes in B with phacoemulsification had a significantly higher IOP on day 1 compared to B (23.2 ± 14.3 versus 17.9 ± 11.4, P = 0.041). During the one-year follow-up, 7 (13.7%) patients in BT group and 18 (35.2%) in B group experienced hypotony (P = 0.04). No dangerous hypotony or hypertension occurred in BT group. The mean BCVA at baseline was 0.64 ± 0.85 logMAR and changed to 0.55 ± 0.75 logMAR in BT and B groups, respectively (P = 0.663). The corresponding numbers for the final follow-up visit was 0.72 ± 1.07 and 0.63 ± 0.97 logMAR, respectively (P = 0.668). CONCLUSION: We observed similar rates of success and IOP reduction using BT and B techniques. BT group needed fewer glaucoma medications. Tube fenestration was unnecessary in BT group resulting in less postoperative ocular hypotony and hypertension. The results of our study indicate that additional trabectome procedure makes Baerveldt glaucoma implant safer, easier to handle, and more predictable in the most vulnerable patients with advanced glaucoma.

Lamina Cribrosa Capillaries Straighten as Intraocular Pressure Increases.

Purpose: The purpose of this study was to visualize the lamina cribrosa (LC) capillaries and collagenous beams, measure capillary tortuosity (path length over straight end-to-end length), and determine if capillary tortuosity changes when intraocular pressure (IOP) increases. Methods: Within 8 hours of sacrifice, 3 pig heads were cannulated via the external ophthalmic artery, perfused with PBS to remove blood, and then perfused with a fluorescent dye to label the capillaries. The posterior pole of each eye was mounted in a custom-made inflation chamber for control of IOP with simultaneous imaging. Capillaries and collagen beams were visualized with structured light illumination enhanced imaging at IOPs from 5 to 50 mm Hg at each 5 mm Hg increment. Capillary tortuosity was measured from the images and paired two-sample t-tests were used to assess for significant changes in relation to changes in IOP. Results: Capillaries were highly tortuous at 15 mm Hg (up to 1.45). In all but one eye, tortuosity decreased significantly as IOP increased from 15 to 25 mm Hg (P < 0.01), and tortuosity decreased significantly in every eye as IOP increased from 15 to 40 mm Hg (P < 0.01). In only 16% of capillaries, tortuosity increased with elevated IOP. Capillaries had a surprisingly different topology from the collagen beams. Conclusions: Although high capillary tortuosity is sometimes regarded as potentially problematic because it can reduce blood flow, LC capillary tortuosity may provide slack that mitigates against reduced flow and structural damage caused by excessive stretch under elevated IOP. We speculate that low capillary tortuosity could be a risk factor for damage under high IOP.

Ripasudil in a Model of Pigmentary Glaucoma.

Purpose: To investigate the effects of Ripasudil (K-115), a Rho-kinase inhibitor, in a porcine model of pigmentary glaucoma. Methods: In vitro trabecular meshwork (TM) cells and ex vivo perfused eyes were subjected to pigment dispersion followed by K-115 treatment (PK115). PK115 was compared to controls (C) and pigment (P). Cytoskeletal alterations were assessed by F-actin labeling. TM cell phagocytosis of fluorescent targets was evaluated by flow cytometry. Cell migration was studied with a wound-healing assay. Intraocular pressure was continuously monitored and compared to after the establishment of the pigmentary glaucoma model and after treatment with K-115. Results: The percentage of cells with stress fibers increased in response to pigment but declined sharply after treatment with K-115 (P: 32.8% ± 2.9%; PK115: 11.6% ± 3.3%, P < 0.001). Phagocytosis first declined but recovered after K-115 (P: 25.7% ± 2.1%, PK115: 33.4% ± 0.8%, P <0.01). Migration recuperated at 12 hours with K-115 treatment (P: 19.1 ± 4.6 cells/high-power field, PK115: 42.5 ± 1.6 cells/high-power field, P < 0.001). Ex vivo, eyes became hypertensive from pigment dispersion but were normotensive after treatment with K-115 (P: 20.3 ± 1.2 mm Hg, PK115: 8.9 ± 1.7 mm Hg; P < 0.005). Conclusions: In vitro, K-115 reduced TM stress fibers, restored phagocytosis, and restored migration of TM cells. Ex vivo, K-115 normalized intraocular pressure. Translational Relevance: This ex vivo pigmentary glaucoma model provides a readily available basis to investigate new drugs such as the rho-kinase inhibitor studied here.

Comparison of a second-generation trabecular bypass (iStent inject) to ab interno trabeculectomy (Trabectome) by exact matching.

PURPOSE: To achieve a highly balanced comparison of trabecular bypass stenting (IS2, iStent inject) with ab interno trabeculectomy (T, Trabectome) by exact matching. METHODS: Fifty-three IS2 eyes were matched to 3446 T eyes. Patients were matched using exact matching by baseline intraocular pressure (IOP), the number of glaucoma medications, and glaucoma type, and using nearest neighbor matching by age. Individuals without a close match were excluded. All surgeries were combined with phacoemulsification. RESULTS: A total of 78 eyes (39 in each group) could be matched as exact pairs with a baseline IOP of 18.3 ± 5.1 mmHg and glaucoma medications of 2.7 ± 1.2 in each. IOP in IS2 was reduced to 14.6 ± 4.2 mmHg at 3 months and in T to a minimum of 13.1 ± 3.2 mmHg at 1 month. In IS2, IOP began to rise again at 6 months, eventually exceeding baseline. At 24 months, IOP in IS2 was 18.8 ± 9.0 mmHg and in T 14.2 ± 3.5 mmHg. IS2 had a higher average IOP than T at all postoperative visits (p < 0.05 at 1, 12, 18 months). Glaucoma medications decreased to 2.0 ± 1.5 in IS2 and to 1.5 ± 1.4 in T. CONCLUSION: T resulted in a larger and sustained IOP reduction compared with IS2 where a rebound occurred after 6 months to slightly above preoperative values.

Dose-dependent effects of netarsudil, a Rho-kinase inhibitor, on the distal outflow tract.

PURPOSE: To characterize the effects of netarsudil on the aqueous humor outflow tract distal to the trabecular meshwork (TM). We hypothesized that netarsudil increases outflow facility in eyes with and without circumferential ab interno trabeculectomy (AIT) that removes the TM. METHODS: Sixty-four porcine anterior segment cultures were randomly assigned to groups with (n = 32) and without circumferential AIT (n = 32). Cultures were exposed to 0.1, 1, and 10 µM netarsudil (N = 8 eyes per concentration). For each concentration, IOP and vessel diameters were compared with their respective pretreatment baselines. Outflow tract vessel diameters were assessed by spectral-domain optical coherence tomography (SDOCT) and rendered in 4D (XYZ time series). RESULTS: Netarsudil at 1 µM reduced IOP both in eyes with TM (- 0.60 ± 0.24 mmHg, p = 0.01) and in eyes without TM (- 1.79 ± 0.42 mmHg, p < 0.01). At this concentration, vessels of the distal outflow tract dilated by 72%. However, at 0.1 µM netarsudil elevated IOP in eyes with TM (1.59 ± 0.36 mmHg, p < 0.001) as well as in eyes without TM (0.23 ± 0.32 mmHg, p < 0.001). Vessels of the distal outflow tract constricted by 31%. Similarly, netarsudil at a concentration of 10 µM elevated IOP both in eyes with TM (1.91 ± 0.193, p < 0.001) and in eyes without TM (3.65 ± 0.86 mmHg, p < 0.001). At this concentration, outflow tract vessels constricted by 27%. CONCLUSION: In the porcine anterior segment culture, the dose-dependent IOP changes caused by netarsudil matched the diameter changes of distal outflow tract vessels. Hyper- and hypotensive properties of netarsudil persisted after TM removal.

3D-Reconstruction of the human conventional outflow system by ribbon scanning confocal microscopy.

PURPOSE: The risk for glaucoma is driven by the microanatomy and function of the anterior segment. We performed a computation-intense, high-resolution, full-thickness ribbon-scanning confocal microscopy (RSCM) of the outflow tract of two human eyes. We hypothesized this would reveal important species differences when compared to existing data of porcine eyes, an animal that does not spontaneously develop glaucoma. METHODS: After perfusing two human octogenarian eyes with lectin-fluorophore conjugate and optical clearance with benzyl alcohol benzyl benzoate (BABB), anterior segments were scanned by RSCM and reconstructed in 3D for whole-specimen rendering. Morphometric analyses of the outflow tract were performed for the trabecular meshwork (TM), limbal, and perilimbal outflow structures and compared to existing porcine data. RESULTS: RSCM provided high-resolution data for IMARIS-based surface reconstruction of outflow tract structures in 3D. Different from porcine eyes with an abundance of highly interconnected, narrow, and short collector channels (CCs), human eyes demonstrated fewer CCs which had a 1.5x greater cross-sectional area (CSA) and 2.6x greater length. Proximal CC openings at the level of Schlemm's canal (SC) had a 1.3x larger CSA than distal openings into the scleral vascular plexus (SVP). CCs were 10.2x smaller in volume than the receiving SVP vessels. Axenfeld loops, projections of the long ciliary nerve, were also visualized. CONCLUSION: In this high-resolution, volumetric RSCM analysis, human eyes had far fewer outflow tract vessels than porcine eyes. Human CCs spanned several clock-hours and were larger than in porcine eyes. These species differences may point to factors downstream of the TM that increase our vulnerability to glaucoma.

Intraocular pressure reduction in a pigmentary glaucoma model by Goniotome Ab interno trabeculectomy.

PURPOSE: To investigate whether microsurgical excision of trabecular meshwork (TM) in an ex vivo pigmentary glaucoma model can normalize the hypertensive phenotype. METHODS: Eight eyes of a porcine pigmentary glaucoma model underwent 90° of microsurgical TM excision with an aspirating dual-blade (Goniotome (G)). 24 hours later, additional 90° of TM were removed. Anterior segments with sham surgeries served as the control (C). Outflow facility and intraocular pressure (IOP) were analyzed. Histology with hematoxylin and eosin (H&E) was obtained. RESULTS: After the first 90° TM excision, IOP was significantly lower in G (10.2±2.4 mmHg, n = 7) than C (20.0±2.0mmHg, n = 8, P<0.01). Outflow facility in G (0.38±0.07 µl/min/mmHg) was higher than C (0.16±0.02 µl/min/mmHg, P<0.01). After the second 90° TM excision, IOP in G (6.46±0.81 mmHg, n = 7) was significantly lower than C (20.3±1.7 mmHg, n = 8, P<0.001), while the outflow facility in G (0.50±0.05 µl/min/mmHg, n = 7) was higher than C (0.16±0.01 µl/min/mmHg, n = 8, P<0.001). Compared to the first excision, excision of an additional 90° did not change of IOP (P = 0.20) or outflow facility (P = 0.17) further. CONCLUSIONS: Excision of 90° of TM in a pigmentary glaucoma model using an aspirating dual-blade decreased IOP and increased outflow facility.

Retrospective evaluation of two-year results with a filtering trabeculotomy in comparison to conventional trabeculectomy by exact matching.

Background: To compare two-year results of a filtering trabeculotomy (FTO) to conventional trabeculectomy (TE) in open-angle glaucoma by exact matching. Methods: 110 patients received an FTO and 86 a TE. FTO avoided the need for an iridectomy due to a preserved trabeculo-descemet window anterior to the scleral flap. TE employed a trabecular block excision and iridectomy. Mitomycin C was used in both. FTO and TE were exact matched by baseline intraocular pressure (IOP) and the number of glaucoma medications. Complete and qualified success (IOP ≤18 mmHg and IOP reduction ≥ 30%, with or without medication) were primary endpoints. IOP, visual acuity (BCVA), complications and intervention were secondary endpoints. Results: 44 FTO were exact matched to 44 TE. The IOP baseline in both groups was 22.5±4.7 mmHg on 3±0.9 medications. At 24 months, complete success was reached by 59% in FTO and 66% in TE, and qualified success by 59% in FTO and 71% in TE. In FTO, IOP was reduced to 12.4±4.3 mmHg at 12 months and 13.1±4.1 mmHg at 24 months. In TE, IOP was 11.3±2.2 mmHg at 12 months and 12.0±3.5 mmHg at 24 months. Medications could be reduced at 24 months to 0.6±1.3 in FTO and 0.2±0.5 in TE. There were no significant differences between the two groups in IOP, medications, complications or interventions at any point. Conclusion: Modifying aqueous flow through a limited trabeculotomy in FTO yielded clinical outcomes similar to traditional TE but allowed to avoid an iridectomy.

Combined vitrectomy, near-confluent panretinal endolaser, bevacizumab and cyclophotocoagulation for neovascular glaucoma - a retrospective interventional case series.

Background: Neovascular glaucoma (NVG) is a severe, potentially blinding disease and a therapeutic challenge. The purpose of this study was to evaluate the safety and efficacy of an integrative surgical approach to neovascular glaucoma. Methods: Retrospective analysis of a one-year follow-up of a consecutive interventional case series of NVG. Eyes underwent transscleral cyclophotocoagulation, pars plana vitrectomy, near-confluent panretinal photocoagulation, and intravitreal bevacizumab. Phakic eyes underwent concomitant cataract surgery. Best-corrected visual acuity (BCVA, logMAR), intraocular pressure (IOP, mmHg), number of glaucoma medication, visual analog pain scale (VAPS, 0-10) were recorded at baseline, and 1, 3, 6, and 12 months. Blind eyes were excluded. Results: Seventy-seven eyes of 77 patients (45 male, 32 female, mean age 73.6±12.2 years) were included. NVG underlying conditions included retinal vein occlusion (41.6%), proliferative diabetic retinopathy (35.1%), central retinal artery occlusion (19.5%), and ocular ischemic syndrome (3.9%). Mean IOP decreased postoperatively from 46.3±10.1 mmHg to 14.5±7.9 mmHg (p<0.001), glaucoma medication from 4.7±1.3 to 1.8±1.8 (p<0.001), and VAPS from 6.0±1.8 to 0. BCVA remained unchanged. Postoperative intraocular inflammation had resolved in all eyes at the one-month follow-up. 71.4% (55/77) eyes did not require additional major interventions during follow-up. Conclusions: A single, comprehensive surgery session lowered IOP significantly, reduced GMS, and controlled pain.

SALT Trial: Steroids after Laser Trabeculoplasty: Impact of Short-Term Anti-inflammatory Treatment on Selective Laser Trabeculoplasty Efficacy.

PURPOSE: This study examined whether short-term use of topical nonsteroidal anti-inflammatory drug (NSAID) or steroid therapy affected the efficacy of selective laser trabeculoplasty (SLT). DESIGN: Double-masked, randomized, placebo-controlled, dual-center, multisurgeon trial. PARTICIPANTS: Patients older than 18 years with intraocular pressure (IOP) of more than 18 mmHg for whom the clinician decided SLT was the appropriately indicated therapy were randomized to 1 of 3 groups in a ratio of 1:1:1 as follows: ketorolac 0.5%, prednisolone 1%, or saline tears. METHODS: After SLT, patients randomized into each group were instructed to use an unmarked drop 4 times daily starting the day of SLT and continuing for 4 additional days. The Kruskal-Wallis test and Wilcoxon rank-sum test were used for continuous variables when comparing 2 or 3 treatment groups, respectively. The Fisher exact test was used for categorical variables. MAIN OUTCOME MEASURES: The primary outcome of this study was IOP at 12 weeks. Secondary outcome measures included IOP at 1 and 6 weeks, patient-reported pain, and detectable anterior chamber inflammation. RESULTS: Ninety-six eyes of 85 patients fit inclusion criteria and were enrolled between the 2 sites. The NSAID, steroid, and placebo groups were similar in baseline demographics and baseline IOP (mean, 23.3±3.9 mmHg; P = 0.57). There was no statistically significant difference in IOP decrease among groups at week 6. Both the NSAID and steroid groups showed a statistically significantly greater decrease in IOP at week 12 compared with the placebo group (mean, -6.2±3.1 mmHg, -5.2±2.7 mmHg, and -3±4.3 mmHg, respectively; P = 0.02 [analysis of variance] and P = 0.002 [t test] for NSAID vs. placebo groups; P = 0.02 for steroid vs. placebo groups). CONCLUSIONS: Significantly better IOP reduction at 12 weeks was measured in eyes treated with steroid or NSAID drops after SLT. Short-term postoperative use of NSAID or steroid drops may improve IOP reduction after SLT. Longer-term follow-up studies are indicated.

Efficacy and safety of micropulse laser trabeculoplasty for primary open angle glaucoma.

AIM: To evaluate the efficiency and safety of micropulse laser trabeculoplasty (MLT) for primary open angle glaucoma (POAG) patients. METHODS: Retrospective study. POAG patients undergoing MLT in Peking University Third Hospital from June 2016 to November 2017. Seventy-two eyes of 72 POAG patients were enrolled. Only one eye of each patient was treated by MLT. The intraocular pressure (IOP) before MLT and at 1d, 1, 4, 12 and 24wk and glaucoma medication before and after treatment were compared. RESULTS: The IOP was 20.6±5.9 mm Hg before MLT and 20.8±6.8 mm Hg at 2h after MTL. The IOP at 1d, 1, 4, 12 and 24wk was 17.9±4.4, 18.0±4.3, 17.5±3.4, 17.0±2.7, and 16.5±2.9 mm Hg, respectively. The IOP before and after MLT demonstrated a statistically significant difference by ANOVA analyses (F=5.797, P<0.001). Least significant difference t-tests showed there was no statistically significant difference between pre-MLT IOP within 2h after MLT (P=0.207). The statistically significant difference was confirmed between the pre-MLT IOP at 1d, 1, 4, 12 and 24wk after MLT (P=0.006, 0.009, 0.001, <0.001, <0.001, respectively). The number of glaucoma medications before MLT was 1.7±1.4 and 1.5±1.4 24wk after MLT with a significantly statistical difference (t=2.219, P=0.031). CONCLUSION: MLT is effective and safe for POAG patients. No patient experienced IOP spikes after MLT. The IOP 6mo after treatment decreased significantly with less glaucoma medication.

Outflow facility and extent of angle closure in a porcine model.

PURPOSE: To establish the extent of anterior chamber angle circumference needed to maintain a physiological outflow facility (C). This could create a model to investigate focal outflow regulation. METHODS: Twenty anterior segments of porcine eyes were assigned to five groups, each with a different degree of cyanoacrylate-mediated angle closure: 90° (n = 4), 180° (n = 4), 270° (n = 4), 360° (n = 4), and four unoccluded control eyes. The outflow facility was measured at baseline, 3, 12, 24, and 36 h after angle closure. Outflow patterns were evaluated with canalograms and the histomorphology was compared. RESULTS: Baseline outflow facilities of the five groups were similar (F = 0.922, p = 0.477). Occlusion of 360° induced a significant decrease in facility from baseline at all time-points (p ≤ 0.023 at 3, 12, 24, and 36 h). However, no difference from baseline was found in any of the partially occluded (0-270°) groups (F ≥ 0.067, p ≥ 0.296 at 3, 12, 24, and 36 h). The canalograms confirmed the extent of occlusion with flow through the unblocked regions. Histology revealed no adverse effects of blockage on the TM or aqueous plexus in the unoccluded angle portions. The unoccluded TM appeared normal. CONCLUSION: Cyanoacrylate-mediated angle occlusion created a reproducible angle closure model. Ninety degrees of unoccluded anterior chamber angle circumference was sufficient to maintain physiological outflow. This model may help understand how outflow can be regulated in healthy, nonglaucomatous TM.