Bax Contributes to Retinal Ganglion Cell Dendritic Degeneration During Glaucoma

The BCL-2 (B-cell lymphoma-2) family of proteins contributes to mitochondrial-based apoptosis in models of neurodegeneration, including glaucomatous optic neuropathy (glaucoma), which degrades the retinal ganglion cell (RGC) axonal projection to the visual brain. Glaucoma is commonly associated with increased sensitivity to intraocular pressure (IOP) and involves a proximal program that leads to RGC dendritic pruning and a distal program that underlies axonopathy in the optic projection. While genetic deletion of the Bcl2-associated X protein (Bax-/-) prolongs RGC body survival in models of glaucoma and optic nerve trauma, axonopathy persists, thus raising the question of whether dendrites and the RGC light response are protected. Here, we used an inducible model of glaucoma in Bax-/- mice to determine if Bax contributes to RGC dendritic degeneration. We performed whole-cell recordings and dye filling in RGCs signaling light onset (αON-Sustained) and offset (αOFF-Sustained). We recovered RGC dendritic morphologies by confocal microscopy and analyzed dendritic arbor complexity and size. Additionally, we assessed RGC axon function by measuring anterograde axon transport of cholera toxin subunit B to the superior colliculus and behavioral spatial frequency threshold (i.e., spatial acuity). We found 1 month of IOP elevation did not cause significant RGC death in either WT or Bax-/- retinas. However, IOP elevation reduced dendritic arbor complexity of WT αON-Sustained and αOFF-Sustained RGCs. In the absence of Bax, αON- and αOFF-Sustained RGC dendritic arbors remained intact following IOP elevation. In addition to dendrites, neuroprotection by Bax-/- generalized to αON-and αOFF-Sustained RGC light- and current-evoked responses. Both anterograde axon transport and spatial acuity declined during IOP elevation in WT and Bax-/- mice. Collectively, our results indicate Bax contributes to RGC dendritic degeneration and distinguishes the proximal and distal neurodegenerative programs involved during the progression of glaucoma.

On elevation of intraocular pressure after intravitreal injections

The aim of this work is to emphasize the need to take into account several important biomechanical factors (biometrical parameters of patient, s eyes accuracy of tonometers) as well as the design of the procedure when interpreting clinical data of immediate IOP elevation after intravitreal injections

Management of Intraocular Pressure Elevation After CO2 Laser-Assisted Sclerectomy Surgery in Patients With Primary Open-Angle Glaucoma

Purpose: To report the safety and efficiency of carbon dioxide (CO2) laser-assisted sclerectomy surgery (CLASS) in Chinese patients with primary open-angle glaucoma (POAG) and the management of unexpected postoperative intraocular pressure (IOP) elevation.Methods: This was a prospective case series study. A total of 23 eyes from 23 patients with POAG who underwent CLASS were involved and followed-up for 12 months. The primary outcomes included the changes in best corrected visual acuity (BCVA), IOP, and medications before and after CLASS. The secondary outcomes were success rate and postoperative laser interventions.Results: The mean age of the patient was 42.6 ± 16.0 years. There was no significant change in BCVA and visual field at baseline and 12 months after CLASS. The number of medications was significantly reduced after CLASS. The IOP was also significantly decreased and remained well controlled during the follow-up period, except for a transient elevation at 1 month postoperatively, due to the occurrence of peripheral anterior synechiae (PAS). Generally, 17 patients (73.9%) were treated with neodymium-doped yttrium aluminum garnet (Nd:YAG) laser synechiolysis to remove iris obstruction in the filtration site and seven patients (30.4%) underwent Nd:YAG laser goniopuncture to deal with scleral reservoir reduction. Only one patient (4.3%) received surgical repositioning due to iris incarceration. The complete success rate and total success rate at 12 months were 69.6 and 95.7%, respectively.Conclusion: CLASS was a safe and effective approach for Chinese patients with POAG. Peripheral anterior synechiae (PAS), iris incarceration, and scleral reservoir reduction were common causes of unexpected postoperative IOP elevation. Individualized Nd:YAG laser intervention helps to improve the long-term outcomes after CLASS.

Water-drinking Test in Normal Tension Glaucoma Patients with and without High Myopia

This prospective study aims to evaluate the correlation between myopic severity and normal tension glaucoma (NTG) by investigating IOP changes following water-drinking test (WDT). We reviewed 61 patients with NTG during an interval of three years, of which 31 were highly myopic (HM) and 30 were non-highly myopic (NHM). Basic characteristics such as age, gender, spherical equivalence, baseline IOP, visual field parameters, and average retinal nerve fiber layer thickness were compared between NTG patients with and without high myopia. The IOP parameters obtained following WDT were then compared between the HM and NHM NTG groups. Intragroup analysis revealed significant IOP elevation following WDT within the 45-minute duration in both groups. However, no significant differences in IOP parameters were observed between the HM and NHM NTG groups. In conclusion, although the pattern of IOP fluctuations was different, the extent of IOP fluctuations and peak IOP following WDT was similar between the HM and NHM NTG groups, suggesting that myopic severity probably has a limited role in NTG. Lastly, WDT was an effective tool for eliciting IOP peaks when 24-hour IOP monitoring is not available.

Differing Associations between Optic Nerve Head Strains and Visual Field Loss in Normal- and High-Tension Glaucoma Subjects

Purpose: To study the associations between optic nerve head (ONH) strains under intraocular pressure (IOP) elevation with retinal sensitivity in glaucoma subjects. Design: Clinic based cross-sectional study. Participants: 229 subjects with primary open angle glaucoma (subdivided into 115 high tension glaucoma (HTG) subjects and 114 normal tension glaucoma (NTG) subjects). Methods: For one eye of each subject, we imaged the ONH using spectral-domain optical coherence tomography (OCT) under the following conditions: (1) primary gaze and (2) primary gaze with acute IOP elevation (to approximately 33 mmHg) achieved through ophthalmodynamometry. A 3-dimensional (3D) strain-mapping algorithm was applied to quantify IOP-induced ONH tissue strain (i.e. deformation) in each ONH. Strains in the pre-lamina tissue (PLT) and the retina, the choroid, the sclera and the lamina cribrosa (LC) were associated (using linear regression) with measures of retinal sensitivity from the 24-2 Humphrey visual field test (Carl Zeiss Meditec, Dublin, CA, USA). This was done globally, then locally according to the regionalization scheme of Garway-Heath et al. Main Outcome Measures: Associations between ONH strains and values of retinal sensitivity from visual field testing. Results: For HTG subjects, we found that (1) there were significant negative linear associations between ONH strains and retinal sensitivity (p<0.001) (on average, a 1% increase in ONH strains corresponded to a decrease in retinal sensitivity of 1.1 dB), (2) high strain regions co-localized with anatomically-mapped regions of high visual field loss, (3) the strongest negative associations were observed in the superior region and in the PLT. In contrast, for NTG subjects, no significant associations between strains and retinal sensitivity were observed except in the supero-temporal region of the LC. Conclusion: We found significant negative associations between IOP-induced ONH strains and retinal sensitivity in a relatively large glaucoma cohort. Specifically, HTG subjects who experienced higher ONH strains were more likely to exhibit lower retinal sensitivities. Interestingly, this trend was in general less pronounced in NTG subjects, which could suggest a distinct pathophysiology between the two glaucoma subtypes.

Efficacy of posterior sub-Tenon’s capsule injection compared to intravitreal injection of triamcinolone acetonide for treatment of diabetic macular edema: A systematic review and meta-analysis

Background Diabetic macular edema (DME) is defined as a retinal thickening in one-disc diameter (DD) of the centre of the macula. It is a number of microvascular retinal changes that lead to blood–retinal barrier (BRB) disruption, causing leakage of fluid and plasma components into the inner and outer plexiform layers. Aim of the Work to conduct a systematic review and a meta-analysis estimating the efficacy and complications of posterior sub-Tenon’s capsule injection of triamcinolone acetonide (STTA) compared to intravitreal injection of triamcinolone acetonide (IVTA) for management of DME. Materials and Methods A comprehensive literature search was conducted using the databases Google scholar, PubMed, MEDS, web of science, EMBASE and Cochrane Library for published studies from 1 January 2000 to 1 September 2019.This meta-analysis included ten studies. They were randomized controlled clinical trials (RCTs), and about 343 patients with DME (469 eyes) participated in these studies. Results : This study demonstrated a statistically significant change in the mean of best corrected visual acuity (BCVA) improvement and central macular thickness (CMT) reduction in both groups when comparing the baseline to one- and three-month follow-ups after the injection, though with no statistically significant difference in the IVTA compared to the STTA group. At a six-month follow-up, both groups showed no significant differences in the BCVA and CMT compared to the baseline. Both groups showed no statistical differences in the BCVA or CMT over the follow-up periods. Regarding intraocular pressure (IOP) changes, the present study showed that the mean IOP was elevated in both groups at one- and three-month follow-ups after the injection compared to their baseline. There was a statistically significant difference between both groups at one and three-months. The IOP was more elevated in the IVTA compared to the STTA group. At a six-month follow-up, both groups showed no significant difference in the IOP elevation compared to the baseline. IOP elevation was the most reported adverse effect in all included studies. Cataract formation is also reported in some studies, though no other complications, such as endophthalmitis, vitreous hemorrhage (VH), and/or retinal detachment (RD), are reported in any of the studies. Conclusion : STTA injection has a comparable effect to the IVTA injection and carries a lower risk of intraocular complications. It is considered an easy, safe, and valid alternative to the intravitreal injection for the treatment of DME.

Ocular Decompression Retinopathy after Anterior Chamber Paracentesis for Neovascular Glaucoma

Ocular decompression retinopathy (ODR) is a rare complication associated with intraocular pressure (IOP)-lowering interventions. We report a case of neovascular glaucoma in the left eye with marked IOP elevation (33 mmHg in the left eye). The IOP in the left eye did not improve despite medical treatment. Paracentesis of the left eye was then performed, and the IOP in the left eye decreased to 9 mmHg. One day after the procedure, several intraretinal hemorrhages, Roth spots, and subhyaloid hemorrhages appeared in the fundus of the left eye. Left eye retinopathy was likely ODR because of the rapid decline in IOP.

Adduction Induces Large Optic Nerve Head Deformations in Subjects with Normal Tension Glaucoma

Purpose: To assess optic nerve head (ONH) deformations and strains during adduction, abduction, and intraocular pressure (IOP) elevation in subjects with high-tension glaucoma (HTG) and normal-tension glaucoma (NTG). Design: Clinic-based cross-sectional study. Participants: 114 HTG subjects and 114 NTG subjects. Methods. We recruited 228 subjects (114 subjects with HTG [pre-treatment IOP > 21mmHg] and 114 with NTG [pre-treatment IOP < 21mmHg]). For each subject, we imaged the ONH using spectral-domain optical coherence tomography (OCT) under the following conditions: (1) primary gaze, (2) 20 degree adduction, (3) 20 degree abduction, and (4) primary gaze with acute IOP elevation (to approximately 33 mmHg) achieved through ophthalmodynamometry. For each OCT volume, we automatically segmented the prelaminar tissue (PLT), the choroid, the sclera and the lamina cribrosa (LC) using a deep learning algorithm. We also digitally aligned the OCT volumes obtained from (2)-(4) to the primary gaze volume (1) before performing digital volume correlation (DVC) analysis to quantify IOP- and gaze-induced ONH tissues three-dimensional displacements and effective strain (a local measure of tissue deformation) for all scenarios. Main Outcome Measures: Three-dimensional ONH displacements and strains. Results: Across all subjects, adduction generated high effective strain (4.2 +- 1.4%) in the ONH tissues with no significant difference (p>0.05) with those induced by IOP elevation (4.5 +- 1.5%); while abduction generated significantly lower (p = 0.014) effective strain (3.8 +- 1.1%). Interestingly, the LC of HTG subjects exhibited significantly higher effective strain than those of NTG subjects under IOP elevation (HTG:4.6 +- 1.7% vs NTG:4.1 +- 1.5%, p = 0.047). Conversely, the LC tissue of NTG subjects exhibited significantly higher effective strain than those of HTG subjects under adduction (NTG: 4.9 +- 1.9% vs HTG: 4.0 +- 1.4%, p = 0.041). Conclusion: We found that adduction produced comparable strains and displacements as IOP elevation. We also found that NTG subjects experienced higher strains due to adduction than HTG subjects, while HTG subjects experienced higher strain due to IOP elevation than NTG subjects - and that these differences were most pronounced in the LC tissue.

Real-time measurement of intraocular pressure variation during automatic intravitreal injections: An ex-vivo experimental study using porcine eyes

Purpose To measure needle insertion force and change in intraocular pressure (IOP) in real-time during intravitreal injection (IVI). The effects of needle size, insertion speed, and injection rate to IOP change were investigated. Methods Needle insertion and fluid injection were performed on 90 porcine eyeballs using an automatic IVI device. The IVI conditions were divided according to needle sizes of 27-gauge (G), 30G, and 33G; insertion speeds of 1, 2, and 5 mm/s; and injection rates of 0.01, 0.02, and 0.05 mL/s. Insertion force and IOP were measured in real-time using a force sensor and a pressure transducer. Results The peak IOP was observed when the needle penetrated the sclera; the average IOP elevation was 96.3, 67.1, and 59.4 mmHg for 27G, 30G, and 33G needles, respectively. An increase in insertion speed caused IOP elevation at the moment of penetration, but this effect was reduced as needle size decreased: 109.8–85.9 mmHg in 27G for 5–1 mm/s (p = 0.0149) and 61.8–60.7 mmHg in 33G for 5–1 mm/s (p = 0.8979). Injection speed was also related to IOP elevation during the stage of drug injection: 16.65 and 11.78 mmHg for injection rates of 0.05 and 0.01 mL/s (p < 0.001). Conclusion The presented data offers an understanding of IOP changes during each step of IVI. Slow needle insertion can reduce IOP elevation when using a 27G needle. Further, the injection rate must be kept low to avoid IOP elevations during the injection stage.