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.

The use of intraluminal PRESERFLO stenting in avoiding early postoperative hypotony.

PURPOSE: Postoperative hypotony following PRESERFLO MicroShunt (PMS) implantation is a frequent cause of complications such as choroidal detachment and hypotony maculopathy. This study aims at evaluating the impact of intraluminal stenting of the PMS during the early postoperative period. METHODS: We retrospectively analyzed the data of 97 patients who underwent PMS implantation with intraoperative placement of a Nylon 10-0 suture as intraluminal stent (PStent) and compared the outcomes to those of an existing database of the traditional MicroShunt implantation technique (PTrad, n = 120). The primary outcome measure was the intraocular pressure (IOP) at one week postoperatively. As a secondary outcome measure, adverse hypotony, defined as an IOP ≤ 5 mmHg with significant choroidal effusion and/or anterior chamber shallowing or the presence of macular folds was also assessed. Additionally, the time to stent removal and the IOP one week after stent removal were reported. RESULTS: Preoperative median IOP was 25.0 (20.5-30.3) mmHg in PStent and 25.0 (19.3-32.0) mmHg in PTrad (p = 0.62). One week after surgery, the median IOP dropped to 10.0 (8.0-13.0) mmHg in PStent and 7.0 (5.0-9.0) in PTrad (p < 0.01). At one month, the IOP was 12.0 (10.0-14.0) mmHg in PStent and 10.0 (8.0-11.0) mmHg in PTrad (p < 0.01). After 3 months, both groups showed similar median IOP levels of 11.0 (8.0-13.5) mmHg and 10.0 (9.75-13.0) mmHg in PStent and PTrad, respectively (p = 0.66). The presence of adverse hypotony was significantly lower in PStent compared to PTrad (6.2% vs 15.8%, p < 0.05). In PStent the stent was removed after 30.0 (21.0-42.5) days. One week after stent removal the mean IOP drop was 6.1 ± 0.5 mmHg (p < 0.01). CONCLUSION: In the early follow-up period, intraluminal stenting of the PMS appears to be safe and effective in controlling the IOP while reducing early postoperative hypotony. Surgical success is not compromised by stent placement. Based on our data, it is recommended to remove the suture two to six weeks after surgery for most patients with uncomplicated postoperative clinical findings.

[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.

Standard anterior peritomy versus a small posterior incision for the implantation of the PRESERFLO microshunt.

PURPOSE: To compare two approaches for the implantation of the PRESERFLO microshunt: an anterior approach (A) with a 6-8-mm peritomy and a posterior approach (P) with a 3-mm incision. METHODS: We retrospectively analyzed 126 patients who received a PRESERFLO microshunt. We compared intraocular pressure (IOP), surgical time, medication count, and postoperative complications over nine months. RESULTS: The baseline IOP was similar in A (21.8 ± 8.5 mm Hg) and P (23.9 ± 8.1 mm Hg) (p = 0.08). Surgical duration was significantly shorter in P (10 ± 0.4 min) than in A (26 ± 0.8 min) (p < 0.001). Postoperative IOP levels were comparable in A (10.8 ± 5.9 mm Hg) and P (10.6 ± 4.5 mm Hg) at 30 days (p = 0.62) and throughout the study (all intra-group p-values > 0.08). The preoperative medication count was 3.2 ± 1.3 drops in A and 3.3 ± 1.0 drops in P (p = 0.4). Postoperative values were 0.2 ± 0.6 in A and 0.3 ± 0.7 in P at nine months. There were no significant differences in complications and surgical revisions between groups (p-values > 0.05). CONCLUSION: Both techniques achieved satisfactory IOP and medication count reductions and had similar safety profiles, but the posterior incision technique was 2.6 times faster than the anterior incision technique.

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.

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.

Morphological Macular Changes Under Brolucizumab Treatment for Neovascular Age-Related Macular Degeneration Refractory to Previous Anti-VEGF Treatment Compared with Treatment-Naive Eyes.

Purpose: To evaluate the morphological macular changes and fluid dynamics under brolucizumab treatment in eyes refractory to previous anti-vascular endothelial growth factor (anti-VEGF) treatment for neovascular age-related macular degeneration (nAMD) compared with treatment-naive eyes. Methods: Retrospective study of all eyes treated with brolucizumab for nAMD between 2020 and 2021 with a fixed injection regimen and one year follow-up. Treatment-naive eyes (TN) were compared with eyes refractory to previous treatment with bevacizumab, ranibizumab, or aflibercept (RT). The primary outcome measure was change of best-corrected visual acuity (BCVA). Secondary outcome measures included foveal central thickness (FCT), presence of intra- or subretinal fluid (IRF, SRF) and presence of pigment epithelial detachment (PED) at any time point during treatment in both groups. Results: Seventeen TN eyes and 17 RT eyes were included. Mean BCVA and mean FCT in TN eyes had significantly improved after 3 months and continued to improve during treatment (p<0.05 and p=0.001, respectively). In RT eyes, mean BCVA did not change significantly while mean FCT had improved after 3 months of treatment and remained stable thereafter. SRF or PED were more frequent in RT eyes compared with TN eyes (p=0.003 and p=0.005, respectively). Conclusion: After 3 months of treatment, the BCVA increased significantly only in TN eyes, while the FCT was significantly reduced in both groups. IRF appears to be similarly seen in both groups after the loading phase; however, SRF and PED appear to be more frequent in the RT eyes compared with TN eyes.

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.