Analysis of the relationship between VEGF, NLRP3 inflammatory complex, EPO levels, and ocular hemodynamics in patients with primary open-angle glaucoma.

OBJECTIVE: Our study aimed to investigate the relationship between vascular endothelial growth factor (VEGF), NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammatory complex, erythropoietin (EPO) levels, and ocular hemodynamics in patients diagnosed with primary open-angle glaucoma (POAG). METHODS: This is a prospective observational study. Patients diagnosed with POAG at The Sixth Hospital of Wuhan hospital between November 2022 and February 2023were enrolled.The patients were categorized into three groups based on the average visual field defect (mean deviation, MD) value: severe injury group (MD > 12 dB, 93 cases), moderate injury group (7 ≤ MD ≤ 12 dB, 89 cases), and mild injury group (MD < 7 dB, 85 cases). The levels of VEGF, NLRP3 inflammatory complex, EPO, and ocular hemodynamics were compared among the groups. Furthermore, the relationship between VEGF, NLRP3, EPO levels, and ocular hemodynamics in patients with POAG was analyzed using Pearson correlation analysis. After adjusting for confounding factors such as age and gender, multivariate Logistic regression analysis was performed with the ocular hemodynamics indexes being used as dependent variables, and VEGF, NLRP3, ASC, Caspase-1, and EPO being used as independent variables. RESULTS: A total of267 patients with POAG were enrolled. There were no significant differences in sex, age, body mass index, systolic blood pressure, diastolic blood pressure, smoking, alcohol consumption, and blood glucose between the two groups (P > 0.05). The levels of NLRP3, ASC, Caspase-1, and EPO in the severe and moderate injury groups were higher than those in the mild injury group, whereas the VEGF levels were lower in the severe and moderate groups compared to the mild group, showing significant differences (P < 0.05). The severe group exhibited higher levels of NLRP3, ASC, Caspase-1, and EPO than the moderate group, while the VEGF levels were lower in the severe group compared to the moderate group, showing significant differences (P < 0.05). The peak systolic velocity(PSV) and resistance index (RI) were higher in the severe and moderate groups than in the mild group, whereas the EDV was significantly lower in the severe and moderate groups compared to the mild group (P < 0.05). The severe group exhibited higher PSV and RI values compared to the moderate group, while the EDV was lower in the severe group compared to the moderate group, showing significant differences (P < 0.05). Pearson correlation analysis was performed to examine the relationship between VEGF, NLRP3, EPO levels, and ocular hemodynamics in patients with POAG. VEGF, NLRP3, ASC, Caspase-1, and EPO showed positive correlations with PSV and RI, and negative correlations with EDV in patients with POAG. Regression analysis showed that VEGF, NLRP3, ASC, Caspase-1 and EPO were significantly correlated with ocular hemodynamics in POAG (all P < 0.001). CONCLUSION: We demonstrated that the levels of VEGF, NLRP3 inflammatory complex, and EPO were highly associated with ocular hemodynamics in patients diagnosed with POAG.

Comparison of safety and effectiveness of micropulse transscleral cyclophotocoagulation and "slow cook" diode laser transscleral cyclophotocoagulation in patients with refractory open-angle glaucoma.

PURPOSE: This study aimed to compare the safety and effectiveness of intraocular pressure reduction between micropulse transscleral cyclophotocoagulation and "slow cook" transscleral cyclophotocoagulation in patients with refractory primary open-angle glaucoma. METHODS: We included patients with primary open angle glaucoma with at least 12 months of follow-up. We collected and analyzed data on the preoperative characteristics and postoperative outcomes. The primary outcomes were a reduction of ≥20% of the baseline value (criterion A) and/or intraocular pressure between 6 and 21 mmHg (criterion B). RESULTS: We included 128 eyes with primary open-angle glaucoma. The preoperative mean intraocular pressure was 25.53 ± 6.40 and 35.02 ± 12.57 mmHg in the micropulse- and "slow cook" transscleral cyclophotocoagulation groups, respectively (p<0.001). The mean intraocular pressure was reduced significantly to 14.33 ± 3.40 and 15.37 ± 5.85 mmHg in the micropulse- and "slow cook" transscleral cyclophotocoagulation groups at the last follow-up, respectively (p=0.110). The mean intraocular pressure reduction at 12 months was 11.20 ± 11.46 and 19.65 ± 13.22 mmHg in the micropulse- and "slow cook" transscleral cyclophotocoagulation groups, respectively (p<0.001). The median preoperative logMAR visual acuity was 0.52 ± 0.69 and 1.75 ± 1.04 in the micropulse- and "slow cook" transscleral cyclophotocoagulation groups, respectively (p<0.001). The mean visual acuity variation was -0.10 ± 0.35 and -0.074 ± 0.16 in the micropulse- and "slow cook" transscleral cyclophotocoagulation, respectively (p=0.510). Preoperatively, the mean eye drops were 3.44 ± 1.38 and 2.89 ± 0.68 drugs in the micropulse- and "slow cook" transscleral cyclophotocoagulation groups, respectively (p=0.017), but those were 2.06 ± 1.42 and 1.02 ± 1.46 at the end of the study in the "slow cook" and micropulse transscleral cyclophotocoagulation groups, respectively (p<0.001). The success of criterion A was not significant between both groups. Compared with 11 eyes (17.74%) in the "slow cook" transscleral cyclophotocoagulation group, 19 eyes (28.78%) in the micropulse transscleral cyclophotocoagulation group showed complete success (p=0.171). For criterion B, 28 (42.42%) and 2 eyes (3.22%) showed complete success after micropulse- and "slow cook" transscleral cyclophotocoagulation, respectively (p<0.001). CONCLUSION: Both techniques reduced intraocular pressure effectively.

Activation of the ROCK/MYLK Pathway Affects Complex Molecular and Morphological Changes of the Trabecular Meshwork Associated With Ocular Hypertension.

Purpose: The Rho-associated protein kinase and myosin light chain kinase (ROCK/MYLK) pathway undeniably plays a pivotal role in the pathophysiology of primary open-angle glaucoma (POAG). In our study, we utilized both ocular hypertension (OHT) rabbit models and clinical investigations to gain invaluable insights that propel the development of novel treatments targeting proteins and genes associated with the trabecular meshwork (TM), thereby offering promising avenues for the management of POAG. Methods: Following microbead injections into the anterior chamber of the ocular cavity of rabbits, we observed elevated histiocyte numbers and immune scores for MYLK-4/ pMLC-2, alongside a reduction in the void space within the TM. Notably, treatment was performed with 0.1% ITRI-E-(S)-4046, a compound with dual kinase inhibitor (highly specific inhibitor of ROCK1/2 and MYLK4), significantly reduced intraocular pressure (IOP; P < 0.05) and expanded the void space within the TM (P < 0.0001) compared with OHT rabbits. In clinical investigations, we utilized whole transcriptome sequencing to analyze gene expression specifically related to the TM, obtained from patients (5 early-onset and 5 late-onset) undergoing trabeculectomy. Results: Our findings revealed 103 differential expression genes (DEGs) out of 265 molecules associated with the Rho family GTPase pathway, exhibiting a P value of 1.25E-10 and a z-score of -2.524. These results underscore significant differences between the early-onset and late-onset POAG and highlight the involvement of the ROCK/MYLK pathway. Conclusions: These findings underscore the critical involvement of the ROCK/MYLK pathway in both OHT-related and different onsets of POAG, providing valuable insights into the TM-related molecular mechanisms underlying the disease.

Outcomes of Gonioscopy-Assisted Transluminal Trabeculotomy in Eyes With Prior Failed Glaucoma Surgery.

PRCIS: This study concludes that GATT can be an effective and safe surgical alternative for managing IOP in eyes with prior failed glaucoma surgeries, associated with minimal complications. PURPOSE: To report outcomes of gonioscopy-assisted transluminal trabeculotomy (GATT) in eyes with prior failed glaucoma surgery. PATIENTS AND METHODS: A retrospective study involving 30 eyes of 30 patients, all of whom had open angles on gonioscopy, experienced prior glaucoma surgery failures, and subsequently underwent GATT. The primary outcome measure was success defined as complete when the intraocular pressure (IOP) was >5 and ≤21/16 mm Hg without glaucoma medications and qualified with medications. RESULTS: The mean age was 51.8±16.1 years. Twenty-one eyes underwent GATT and 9 eyes underwent phaco-GATT. Twenty-seven eyes had failed trabeculectomy and 3 eyes had failed glaucoma drainage device. Post-GATT, the IOP decreased from 27.1±7 to 16.9±6 mm Hg (P<0.001) at the end of 15 months, with a mean drop in AGM from 4.9±1.0 to 2±1.6. At postoperative 1 year, the probability of complete success was 20% (95% CI: 9-43) for an IOP criterion of both 21 and 16 mm Hg. The qualified success probability at 1 year was 82% (67-100) for an IOP criterion of 21 mm Hg and 57% (38-84) for an IOP criterion of 16 mm Hg. Risk factor for failure was older age [hazard ratio (HR): 1.03, 95% CI: 1.01-1.06]. The complications noted were hyphema in 14 eyes (46%), majority resolved within 1 week and all by 2 weeks. None needed any intervention. CONCLUSIONS: This study concludes that GATT can be an effective and safe surgical alternative for managing IOP in eyes with prior failed glaucoma surgeries, associated with minimal complications.

Long-term effectiveness and safety of XEN45 in open-angle glaucoma patients.

BACKGROUND: To investigate the long-term effectiveness and safety of XEN45 implant, either alone or in combination with phacoemulsification, in eyes with open-angle glaucoma (OAG). METHODS: Retrospective and single center study conducted on consecutive OAG patients who underwent a XEN45 implant between February-2017 and December-2021. The primary endpoint was the mean intraocular pressure (IOP) lowering from preoperative values. Surgical success was defined as an IOP-lowering from preoperative values ≥ 20% and an IOP absolute value between 6 and 13 mm Hg, without (Complete-success) or with (Qualified-success) antiglaucoma medications. RESULTS: A total of 158 eyes (34 (21.5%) eyes XEN-solo and 124 (78.5%) XEN + Phaco) were included. The median follow-up time was 28.5 months. In the overall study population, the mean preoperative IOP was significantly lowered from 19.4 ± 6.5 mm Hg to 12.4 ± 5.0 mm Hg. The mean preoperative (95% confidence interval) IOP was significantly lowered from 21.3 (19.3-23.2) mm Hg and 18.8 (17.7-20.0) mm Hg to 12.0 (10.4-13.6) mm Hg and 12.5 (11.6-13.5) mm Hg in the XEN-Solo and XEN + Phaco groups, respectively (p < 0.0001 each, respectively). The mean number of ocular-hypotensive medications was significantly reduced in the overall study sample (from 3.4 ± 0.9 to 0.9 ± 1.3, p < 0.0001), XEN-Solo (from 3.5 ± 1.1 to 0.6 ± 1.0, p < 0.0001, and XEN + Phaco (from 3.4 ± 1.1 to 0.9 ± 1.3, p < 0.0001) groups. Eighty-four (53.2%) eyes were categorized as success, with 49 (58.3%) classified as complete success. Eighty-one (51.3%) eyes underwent needling and 15 (9.5%) eyes required an additional surgical procedure. One (0.6%) eye had endophthalmitis. CONCLUSION: XEN implant, either alone or in combination with phacoemulsification significantly lowered IOP and reduced the need of ocular-hypotensive medication, while maintaining a good safety profile.

[The relationship between intraocular pressure and age-related variations in ocular rigidity]. / Vzaimosvyaz' vnutriglaznogo davleniya s involyutsionnymi kolebaniyami rigidnosti glaza.

PURPOSE: This study aimed to identify the correlation between age-related fluctuations in the average values of rigidity of the fibrous tunic of the eye (FTE) and corresponding ranges of true intraocular pressure (IOP) in healthy eyes and eyes with open-angle glaucoma (OAG); using the identified ranges of FTE rigidity, to establish the appropriate IOP zones for healthy and glaucomatous eyes, taking into account the aging periods as classified by the World Health Organization (WHO). MATERIAL AND METHODS: Ocular-Response Analyzer tonometry was used according to the Koshits-Svetlova dynamic diagnostic method to examine 674 patients with healthy eyes and 518 patients with glaucomatous eyes, aged 18 to 90 years, classified according to the WHO aging periods, and a theoretical analysis was conducted to estimate clinical values of FTE rigidity, the current level of true IOP, and the calculated individual IOP level in a patient's eye during youth. RESULTS: The following IOP level zones were identified for patients with healthy and glaucomatous eyes: low IOP zone (≤13 mm Hg); medium IOP zone (14-20 mm Hg); elevated IOP zone (21-26 mm Hg); high IOP zone (27-32 mm Hg); subcompensated IOP zone (33-39 mm Hg); and decompensated IOP zone (≥40 mm Hg). CONCLUSION: The fundamental physiological criterion "rigidity" does not depend on central corneal thickness and consistently reflects the current level of true IOP. In all examined patients, both with healthy and glaucomatous eyes, healthy and glaucoma eyes with the same level of current rigidity had the same level of IOP. The ability to assign a given healthy or glaucomatous eye to a specific individual IOP zone is particularly important for the polyclinic system.

Effect of brimonidine on vascular density and imagej-derived flow index of optic nerve head and macula in primary open angle glaucoma.

PURPOSE: To study the effect of brimonidine on vascular density and flow index of optic nerve head (ONH) and macula in primary open angle glaucoma (POAG) using optical coherence tomography angiography (OCTA). METHODS: Twenty-three brimonidine-naïve POAG patients were started on brimonidine. They underwent OCTA ONH and macula before commencing brimonidine and one month thereafter. Systemic arterial blood pressure (SABP) and intraocular pressure (IOP) were measured at each visit to calculate mean ocular perfusion pressure (MOPP). The OCT angiograms were analyzed using ImageJ software to calculate ONH and macular flow indices. RESULTS: Thirty-seven eyes (23 patients) with a mean age of 56.7 ± 12.49 years were included of whom 60.8% were males. Brimonidine was associated with an increase in the superficial flow index (SFI) (P-value = 0.02) and optic nerve head flow index (ONHFI) (P-value = 0.01). Also, superficial vascular density (SVD) for whole image, superior-hemi and fovea increased (P-value = 0.03, 0.02, 0.03 respectively). ONH inferior-hemi vascular density decreased (P-value = 0.01) despite an increase in inferior quadrant retinal nerve fiber layer thickness (RNFLT) (P-value = 0.03). There was no statistically significant correlation between flow indices and MOPP at baseline and follow-up. A moderate negative correlation was found between SVD and DVD at the fovea and MOPP at baseline and follow-up (P-value = 0.03, 0.05) (P-value = 0.02, 0.01) respectively. CONCLUSIONS: Brimonidine was associated with an increase in SFI, ONHFI and SVD indicating improved GCC and RNFL perfusion in POAG. Despite the increase in inferior quadrant RNFLT, the concomitant decrease in inferior-hemi ONHVD precluded a conclusion of hemodynamically-mediated improvement of RNFLT.

Open-angle glaucoma and Fuchs dystrophy.

A 62-year-old woman with a history of moderate myopia, long-standing open-angle glaucoma (OAG), and Fuchs dystrophy in both eyes was referred for consultative care. She had prior trabeculectomy in 1984 and 1992 in the left and right eyes, respectively. She is 3 months post-Descemet-stripping endothelial keratoplasty (DSEK) in the left eye, now referred with uncontrolled intraocular pressure (IOP) despite maximum tolerated medical therapy. Current medical therapy for IOP consists of acetazolamide 250 mg by mouth 2 times a day, brimonidine 2 times a day in the left eye, dorzolamide 2 times a day in the left eye, and timolol 2 times a day in the left eye. The patient has a history of presumed steroid response; however, her corneal surgeon has requested that the steroid be continued for the next several months because of the recent DSEK. The IOP in the left eye has ranged from the mid-20s to mid-30s since DSEK. The right eye has consistently had pressure in the low teens and below for many years without topical antihypertensive medications. Examination revealed stable visual acuity at 20/30 and 20/40 in the right and left eyes, respectively, IOP was 12 mm Hg in the right eye and 25 mm Hg in the left eye by Goldman applanation, irregular but reactive pupils without afferent defect, and full confrontational visual fields. Slitlamp examination showed superior low avascular bleb, moderate-to-severe guttae, and posterior chamber IOL in the right eye. The left eye showed superior low diffuse bleb, clear DSEK graft, quiet chamber, superonasal iridectomy, and posterior chamber IOL with an open posterior capsule. The conjunctiva was moderately scarred but a repeat trabeculectomy or Xen Gel stent (Abbvie) appeared possible. The angles were wide open in each eye. Fundus examination was normal aside from myopic, anomalous-appearing nerves with an approximate cup-to-disc ratio of 0.90 in both eyes. Humphrey visual field showed nonspecific changes on the right and moderate nasal defect on the left eye, stable to previous examinations dating back to 2018 (Figure 1JOURNAL/jcrs/04.03/02158034-202407000-00018/figure1/v/2024-07-10T174240Z/r/image-tiff and Figure 2JOURNAL/jcrs/04.03/02158034-202407000-00018/figure2/v/2024-07-10T174240Z/r/image-tiff). Optical coherence tomography (OCT) of the retinal nerve fiber layer (RNFL) revealed moderated thinning in both eyes that was also stable to prior examinations (Figure 3JOURNAL/jcrs/04.03/02158034-202407000-00018/figure3/v/2024-07-10T174240Z/r/image-tiff). Her axial length measured 25.23 and 26.34 mm in the right and left eyes, respectively. Central corneal thickness was 553 µm in the right eye and 563 µm in the left eye before her DSEK procedure. What would be your approach to management of this patient's left eye, addressing the following: Rationale for your procedure of choice? Would you over-rule the corneal surgeon and stop the steroid in an attempt to obviate the need for glaucoma surgery? Does the age of onset of glaucoma affect your surgical decision making? Note that patient age at the time of trabeculectomy was 22 years. Are some procedures better suited for patients after DSEK surgery?

Long-term outcomes of canaloplasty and phaco-canaloplasty in the treatment of open angle glaucoma: a single-surgeon experience.

PURPOSE: To evaluate and compare the long-term outcomes of canaloplasty and phaco-canaloplasty in the treatment of open angle glaucoma and assess the prognostic factors associated with surgical outcome. METHODS: A 48-month retrospective analysis was performed on n = 133 open angle glaucoma eyes treated with canaloplasty and n = 57 open angle glaucoma eyes treated with phaco-canaloplasty by a single surgeon. Surgical success was defined according to six criteria, achieving a target intraocular pressure (IOP) ≤ 21, 18 or 15 mmHg on glaucoma medications (qualified success) or without any further treatment (complete success), including laser therapy or surgery. Kaplan-Meier survival analysis and Cox regression analysis were performed to evaluate surgical success and preoperative factors associated with surgical outcome. Surgical complications in the early postoperative period were compared between canaloplasty and phaco-canaloplasty. RESULTS: Canaloplasty and phaco-canaloplasty significantly reduced postoperative IOP and number of glaucoma medications (p = 0.001 for both). Phaco-canaloplasty showed higher rates of cumulative surgical success over canaloplasty, but only for target IOP ≤ 21 and ≤ 18 (p = 0.018 and p = 0.011, respectively). A preoperative number of > 4 glaucoma medications predicted surgical failure. Phaco-canaloplasty was associated with a higher rate of IOP peaks in the first month compared with canaloplasty (40.4% vs 12.7%, p = 0.000). CONCLUSION: Canaloplasty and phaco-canaloplasty demonstrated long-term efficacy in the treatment of open angle glaucoma, with phaco-canaloplasty showing higher rates of surgical success compared to canaloplasty, but not for target IOPs lower than 16 mmHg. Patients on more than 4 preoperative glaucoma medications may not be good candidates for canaloplasty and may benefit from other surgical options.

Contributions of Brain Microstructures and Metabolism to Visual Field Loss Patterns in Glaucoma Using Archetypal and Information Gain Analyses.

Purpose: To investigate the contributions of the microstructural and metabolic brain environment to glaucoma and their association with visual field (VF) loss patterns by using advanced diffusion magnetic resonance imaging (dMRI), proton magnetic resonance spectroscopy (MRS), and clinical ophthalmic measures. Methods: Sixty-nine glaucoma and healthy subjects underwent dMRI and/or MRS at 3 Tesla. Ophthalmic data were collected from VF perimetry and optical coherence tomography. dMRI parameters of microstructural integrity in the optic radiation and MRS-derived neurochemical levels in the visual cortex were compared among early glaucoma, advanced glaucoma, and healthy controls. Multivariate regression was used to correlate neuroimaging metrics with 16 archetypal VF loss patterns. We also ranked neuroimaging, ophthalmic, and demographic attributes in terms of their information gain to determine their importance to glaucoma. Results: In dMRI, decreasing fractional anisotropy, radial kurtosis, and tortuosity and increasing radial diffusivity correlated with greater overall VF loss bilaterally. Regionally, decreasing intra-axonal space and extra-axonal space diffusivities correlated with greater VF loss in the superior-altitudinal area of the right eye and the inferior-altitudinal area of the left eye. In MRS, both early and advanced glaucoma patients had lower gamma-aminobutyric acid (GABA), glutamate, and choline levels than healthy controls. GABA appeared to associate more with superonasal VF loss, and glutamate and choline more with inferior VF loss. Choline ranked third for importance to early glaucoma, whereas radial kurtosis and GABA ranked fourth and fifth for advanced glaucoma. Conclusions: Our findings highlight the importance of non-invasive neuroimaging biomarkers and analytical modeling for unveiling glaucomatous neurodegeneration and how they reflect complementary VF loss patterns.

Corneal endothelial density loss in patients after gonioscopy­assisted transluminal trabeculotomy.

PURPOSE: To compare short-term changes in corneal endothelial cells after gonioscopy-assisted transluminal trabeculotomy(GATT). METHODS: This retrospective comparative study included 138 patients(138 eyes), and 98 of these patients underwent GATT procedure and 40 underwent SLT procedure as a control group. Changes in the corneal endothelium in patients who underwent GATT and SLT were analyzed retrospectively. Endothelial changes in the central cornea were examined using specular microscopy before and 6 months after the GATT and SLT procedure. Intraocular pressure(IOP), number of glaucoma medications, and side effects were evaluated at visits before and after two methods. RESULTS: One hundred and thirty-eight eyes of 138 patients with a mean age of 62.9±12.7 years in the SLT group and 62.5±11.8 years in the GATT group were included in this study. Pre-procedure mean ± SD IOP was 27.7±3.6 mmHg and 27.4±5.3 mmHg (p=0.173) 2.8±0.5 and 2.9±0.8 (p=0.204) glaucoma drugs are in the SLT and GATT group, respectively. The mean corneal endothelial cell density (CECD) in the SLT group was 2433.1±581.4 cells/mm2 before the procedure and 2435.1±585 cells/mm2 6 months after the procedure, a change of 0.1±0.6% which was not statistically significant (p>0.967).The mean CECD at baseline in the GATT group was 2443.4±508.2 cells/mm2 and decreased to 2290.2±527.7 cells/mm2 6 months after this procedure, representing a cell loss of 6,2±9,1% (p<0.001). CONCLUSION: GATT caused more CECD damage than SLT at the sixth month after the procedure. Considering the loss of CECD in candidates for GATT, sufficient number of endothelial cells in the central cornea is recommended.

Underlying Microstructure of the Lamina Cribrosa at the Site of Microvasculature Dropout.

Purpose: To determine the microstructure of the lamina cribrosa (LC) associated with microvasculature dropout (MvD) of the deep optic nerve head (ONH) in primary open-angle glaucoma (POAG) and to identify factors related to the presence of MvD. Methods: POAG eyes that exhibited MvD in the LC (MvD-LC) or MvD in the peripapillary choroid (MvD-PC) underwent optical coherence tomography and optical coherence tomography angiography (OCTA) to evaluate the structure and microvasculature of the deep ONH, respectively. The presence of MvD-LC or MvD-PC was determined using en face OCTA images of the deep ONH. The sectoral LC thickness (LCT) and LC curvature index (LCCI) (at MvD-LC site, when applicable), the mean LCT and LCCI of the global ONH, and other clinical characteristics were measured and compared between eyes with and without MvD-LC. Results: The study included 93 eyes with and 51 without MvD-LC. The presence of MvD-LC was associated with lower sectoral LCT (odds ratio [OR] = 0.96, P < 0.001) and mean LCT (OR = 0.97, P = 0.032), larger visual field pattern standard deviation (PSD; OR = 1.20, P = 0.038), and higher pretreatment intraocular pressure (IOP; OR = 1.22, P = 0.012). Fifteen percent of the eyes with MvD-LC (14/93) did not present MvD-PC. Those eyes had younger age (P = 0.043), thicker juxtapapillary choroid (P = 0.018), larger sectoral LCCI (P = 0.040), thicker retinal nerve fiber layer (P = 0.024), smaller PSD (P = 0.008), and higher pretreatment IOP (P = 0.006) than those with both MvD-LC and MvD-PC. Conclusions: MvD-LC was associated with a localized morphologic alteration of the LC, and eyes with MvD-LC tended to have a higher pretreatment IOP. The clinical implications of MvD-LC should differ from those of MvD-PC in eyes with POAG.

OCT angiographic evaluation of changes in macula and optic nerve head vessel density after a water drinking test in glaucomatous and healthy eyes.

PURPOSE: To evaluate the effects of a water drinking test (WDT) on the intraocular pressure (IOP) and vascular density of the optic nerve head and macula in healthy individuals and those with primary open glaucoma using optical coherence tomography angiography. METHODS: In this prospective comparative study, 30 healthy patients and 44 POAG subjects were divided into two groups. The study's outcome measures were the IOP and vessel density of the optic nerve and macular area. After ingesting 1000 ml of water in 5 min, the effect of the WDT on the IOP and the vascular density of the macular area and optic nerve head were measured at baseline and then 20, 40, and 60 min later at intervals of 20 min. RESULTS: The initial IOP in the healthy and glaucomatous eye groups was comparable (15.94 ± 2.6 and 16.87 ± 4.21 mmHg, respectively, P = 0.506). The IOP of both groups peaked at 40' measurements. POAG eyes had significantly higher IOP elevation (4.34 ± 0.30 vs. 2.24 ± 0.30 mmHg, P < 0.001). The glaucomatous eyes had lower radial peripapillary capillary (RPC) and whole macular superficial capillary plexus (SCP) densities at baseline (48.55 ± 5.99 vs. 51.33 ± 3.75) and (48.92 ± 3.41 vs. 45.29 ± 5.29), respectively (P < 0.001). After the WDT, the change in vessel density between groups in the RPC, whole superficial, and deep capillary plexuses was insignificant (SCP and DCP of 0.66 and 0.70, respectively, P = 0.16). CONCLUSION: The WDT caused a significant IOP jump in both glaucomatous and healthy eyes, but generally, the alterations in the glaucomatous eyes were more pronounced. The changes in vascular density in the macula and optic nerve head were similar between the groups.

Plasma rich in growth factors (PRGF) technology as adjuvant to Ab Externo trabeculectomy.

PURPOSE: Plasma rich in growth factors (PRGF) technology creates blood-derived products with growth factors that promote wound healing and regeneration. The goal of this study was to assess the potential role of PRGF products as wound modulators in trabeculectomy. Our premise is that due to PRGF's regenerative and antifibrotic properties, its use in trabeculectomy may produce a more physiological bleb, without altering IOP reduction. METHODS: A retrospective, longitudinal study was conducted in a Hospital in Portugal. Patients with eyes with open angle glaucoma were included. Trabeculectomy was performed on all patients using PRGF membrane (mPRGF) under the conjunctiva, as adjuvant. Data regarding patients' demographics and number of medications used, was collected. Intraocular pressure (IOP) before surgery, 8 days, 1 month, 3 month, 6 month, 9 month and 1 year after surgery was recorded. Bleb morphology was classified according to Moorfields Bleb Grading System 6 months after surgery. RESULTS: Nine eyes of 9 patients were enrolled. Mean age was 71 ± 5.1 years old. Six were male. Mean IOP decreased from 24.0 ± 8.8 mmHg pre-surgery to 12.9 ± 2.6 mmHg at one year follow-up. The number of hypotensive drugs (mean ± SD) was 4.3 ± 0.9 preoperatively and 0.8 ± 1.1 at 1-year. Complete success was defined as IOP equal to or less than 21 mm Hg without ocular hypotensive medications and qualified success as IOP equal to or less than 21 mm Hg with medications. Complete success was 66.7% and qualified success was 100% at 1 year follow-up. CONCLUSION: In our study, trabeculectomy with mPRGF demonstrated both safety and efficacy. Low values of bleb height (1.6 ± 0.8) were recorded. mPRGF could improve wound healing and produce a more well-tolerated, favourable bleb, avoiding antimetabolite complications.

Comparison of corneal endothelial cell density reduction between primary open-angle glaucoma and pseudo-exfoliation glaucoma patients at 3 years after Ex-Press® surgery.

PURPOSE: We compared corneal endothelial cell (CED) loss after Ex-Press (EXP) surgery between patients with primary open-angle glaucoma (POAG) and pseudo-exfoliation glaucoma (PEX). PATIENTS AND METHODS: This was a single-facility retrospective study. We included glaucoma patients who had undergone EXP surgery and were followed up > 3 years. We measured the CED before and after (at 12, 24, and 36 months) EXP surgery by noncontact specular microscopy and compared the means of the CED values and CED survival ratios after EXP surgery by paired t-test. RESULTS: We included 119 eyes that underwent EXP surgery, including 60 POAG eyes and 59 PEX eyes. In the POAG group, the mean CED decreased from 2389 ± 321 at baseline to 2230 ± 424 cells/mm2 after 3 years. In the PEX group, the mean CED decreased from 2111 ± 510 at baseline to 1845 ± 628 cells/mm2 after 3 years. At the 3-year follow-up, the CED survival ratio was 93.3 ± 12.5% in the POAG group and significantly lower, at 85.0 ± 19.5%, in the PEX group (p = 0.0064). Two cases in the PEX group developed bullous keratopathy. CONCLUSIONS: EXP surgery decreased the corneal endothelial cell populations in PEX patients faster than POAG patients.

Independent Effects of Blood Pressure on Intraocular Pressure and Retinal Ganglion Cell Degeneration: A Mendelian Randomization Study.

Purpose: To investigate the causal effect of elevated blood pressure on primary open-angle glaucoma (POAG) and POAG endophenotypes. Methods: Two-sample Mendelian randomization (MR) was performed to investigate the causal effect of elevated systolic blood pressure (SBP) (N = 757,601) and diastolic blood pressure (DBP) (N = 757,601) on intraocular pressure (IOP) (N = 139,555), macular retinal nerve fiber layer (mRNFL) thickness (N = 33,129), ganglion cell complex (GCC) thickness (N = 33,129), vertical cup-to-disc ratio (VCDR) (N = 111,724), and POAG liability (Ncases = 16,677, Ncontrols = 199,580). The primary analysis was conducted using the inverse-variance weighted approach. Sensitivity analyses were performed to investigate robustness to horizontal pleiotropy, winner's curse, and collider bias. Multivariable MR was performed to investigate whether any effect of blood pressure on retinal ganglion cell degeneration was mediated through increased IOP. Results: Increased genetically predicted SBP and DBP associated with an increase in IOP (0.17 mm Hg [95% CI = 0.11 to 0.24] per 10 mm Hg higher SBP, P = 5.18 × 10-7, and 0.17 mm Hg [95% CI = 0.05 to 0.28 mm Hg] per 10 mm Hg higher DBP, P = 0.004). Increased genetically predicted SBP associated with a thinner GCC (0.04 µm [95% CI = -0.07 to -0.01 µm], P = 0.018) and a thinner mRNFL (0.04 µm [95% CI = -0.07 to -0.01 µm], P = 0.004), an effect that arises independently of IOP according to our mediation analysis. Neither SBP nor DBP associated with VCDR or POAG liability. Conclusions: These findings support a causal effect of elevated blood pressure on retinal ganglion cell degeneration that does not require intermediary changes in IOP. Targeted blood pressure control may help preserve vision by lowering IOP and, independently, by preventing retinal ganglion cell degeneration, including in individuals with a normal IOP.

A phase III, multicentre, randomised, investigator-masked, cross-over, comparative, non-inferiority trial evaluating the efficacy and tolerability of generic preservative-free Latanoprost (Polpharma S.A.) compared to Xalatan® (Pfizer) in patients with ocular hypertension or primary open-angle glaucoma.

BACKGROUND: Primary open-angle glaucoma (POAG), often associated with increased intraocular pressure (IOP), can lead to permanent damage of the optic nerve, concomitant visual field loss, and blindness. Latanoprost, a prostaglandin F2α analogue, reduces IOP and is used to treat glaucoma. In this clinical trial, we evaluated the efficacy of Latanoprost Polpharma, a generic preservative-free latanoprost 0.05 mg/ml eye drops solution, in lowering IOP when compared to the originator Xalatan® (latanoprost 0.005% ophthalmic solution, Pfizer). METHODS: This was a Phase III, multicentre, randomized, investigator-masked, cross-over, comparative, non-inferiority trial carried out in 5 sites in Hungary and Russia. The primary endpoint was to evaluate the non-inferiority of the test product when compared to the reference product with respect to the differences in the mean diurnal IOP on Day 1 (baseline) and Day 29. The secondary endpoints included efficacy, ocular tolerance, safety, and usability. We recruited adult patients (18-75 years) with open-angle glaucoma or ocular hypertension. RESULTS: Forty-nine patients were randomised and received at least one dose of the test or reference product. A virtually identical reduction of the mean diurnal IOP of 7.04 ± 2.14 mmHg or 7.17 ± 2.11 mmHg was found after treatment with test or reference product, respectively (N = 44). In the intention to treat analysis, the reduction was 7.29 ± 2.53 mmHg (95% CI: 6.55-8.04) or 7.43 ± 2.78 mm Hg (95%CI: 6.61-8.24) after treatment with test or reference product, respectively (N = 47). There were no serious adverse events. CONCLUSIONS: Latanoprost Polpharma was shown to be non-inferior to Xalatan®. Both investigational products were equally well tolerated and safe. The data show a trend in favour of the test product with regards to the severity of hyperaemia and to the velocity of remission of ocular discomfort. Latanoprost Polpharma, being preservative-free, also avoids the cytotoxicity of benzalkonium chloride, the side effects of which may affect patient compliance and lower the quality of life. TRIAL REGISTRATION: The study had the ethical and regulatory approval from the National Institute of Pharmacy and Nutrition (OGYEI, OGYEI/41,779- 11/2018) and the Ethics Committee for Clinical Pharmacology (KFEB) of Hungary and from the Ministry of Healthcare of the Russian Federation (MOH of Russia) prior to the beginning of the study (642/25.12.2018) (clinical trial identification number: 848,300,144/0103/1 - POP03; IND number/EudraCT number: 2018-001727-39).

Evaluation of lamina cribrosa curvature index in different types of glaucoma.

OBJECTIVE: The aim of this study was to evaluate the lamina cribrosa curvature index in different types of glaucoma in comparison with clinical findings and conventional measurement methods. MATERIAL AND METHOD: Patients older than 18 years who were followed up in Glaucoma Unit of Department of Ophthalmology at Firat University Faculty of Medicine, whose disease had been under control at least for 1 year, who had at least three reliable visual fields, whose refractive error was between - 6 and + 5 diopter and who did not have any disease other than glaucoma that would affect the visual field, were included in the study. Clinical and demographic characteristics, visual field, optical coherence tomography and lamina cribrosa curvature index (LCCI) results were evaluated. The study patients were divided into six groups: early-stage primary open-angle glaucoma (POAG) as group 1 and intermediate-advanced stage POAG as group 2, pseudo-exfoliation glaucoma (PEXG) as group 3, normal tension glaucoma (NTG) as group 4, ocular hypertension patients whom subsequently developed POAG as group 5 and healthy control as group 6. RESULTS: A total of 189 eyes of 101 patients were included in our study. Forty-seven patients were male (46.5%) and 54 were female (53.5%). The mean age was 62.43 ± 1.49 years. LCCI, mean deviation (MD), visual field index (VFI), pattern standard deviation (PSD) and retinal nerve fiber layer thickness (RNFL) values were analyzed in all groups and Pearson correlation analysis showed statistically significant correlation between PSD and RNFL measurements with LCCI values in all groups. MD value was correlated with LCCI in groups 2, 3 and 4, while VFI value was correlated with LCCI in all groups except group 5. When the groups were compared with each other according to the Post-Hoc Tamhane test, LCCI measurement showed statistically significant results in accordance with MD, VFI, PSD and RNFL values. CONCLUSION: The LCCI assessment is mostly consistent with conventional tests. In this study, in which different types of glaucoma and healthy subjects were examined simultaneously, LCCI shows promise as a detailed and reliable assessment method.

Double implantation of Xen 45 gel stent in primary open-angle glaucoma: a pilot study.

PURPOSE: To describe the outcomes of double implantation of Xen 45 Gel Stent (Xen) using an ab externo approach with closed conjunctiva. METHODS: Retrospective single-centre case series of primary open-angle glaucoma patients with at least six months of follow-up after implantation of a second Xen in the same eye via ab externo technique without conjunctival opening. RESULTS: Eight pseudophakic eyes of 8 patients were included. Intraocular pressure (IOP) dropped from 30 ± 2.6 mmHg pre-operatively to 22.4 ± 2.3 mmHg one month after the first Xen implant (mean difference: -7.6 mmHg [95% confidence interval: -9.4, -5.9 mmHg], p = 0.0092). A second Xen was then implanted to achieve the target IOP. The procedure showed no significant intraoperative or postoperative complications. The IOP dropped to 16.1 ± 2.7 mmHg six months following this second implant (mean difference: -6.3 mmHg [95% confidence interval: -7.2, -5.3 mmHg], p = 0.0183); however, 3 patients needed medical therapy to further reduce the IOP towards the target value. CONCLUSION: Sequential implantation of two Xen 45 Gel Stents using an ab externo approach with closed conjunctiva appears a promising procedure that showed a favorable safety and efficacy profile in this small case series. This pilot data might pave the way for further studies to evaluate the safety and efficacy of the procedure.