Acute Intraocular Pressure Research Articles

Factors Associated with Retinal Microvasculature Dropout Induced by Elevation of Intraocular Pressure in Primary Open-Angle Glaucoma.

To investigate the risk factors related to decrease in vessel density (VD) observed in primary open-angle glaucoma (POAG), due to acute increase in intraocular pressure (IOP) by an ophthalmodynamometer (OPD). This cross-sectional study involved 42 eyes of participants (22 Controls and 20 POAG patients) that underwent optical coherence tomography angiography (OCT-A) to assess VD in the peripapillary region in three examination sets: primary gaze position (1), 25-degree adduction (2) and 25-degree adduction with OPD compression (3). Individual relationships between IOP levels and changes in the superficial complex VD were evaluated after image processing and exclusion of large retinal vessels. Multivariable regression analysis was used to verify factors associated with differences in VD induced by IOP elevation. A significant increase in IOP was induced by OPD compression during adduction (mean ± SD, Control: + 13.8 ± 2.8; POAG: + 13.4 ± 2.1mmHg). Only during IOP elevation (set 3), a significant VD decrease was observed both in POAG eyes (p = 0.008) and controls (p = 0.022). Baseline IOP (p = 0.022), maximum IOP (p = 0.003), and scleral rigidity (p = 0.029) were significantly associated with VD decreases in eyes with POAG. No changes were observed in VD during adduction gaze exclusively. Acute IOP elevation induced with OPD, but not adduction gaze, decreased peripapillary VD measured with OCT-A imaging. IOP levels and scleral rigidity significantly affected VD reduction in POAG patients. Thus, high scleral rigidity may decrease the ability of the globe to dampen the well-known effects of IOP fluctuation on glaucoma onset and progression. What is known Decrease vascular density in the peripapillary retina was associated with POAG, but factors related to the vascular response to elevated IOP are unexplored. What is new OCT-A quantification shows decreases in vascular density of the superficial layers of the peripapillary retina during an acute elevation in IOP. High IOP levels and scleral rigidity significantly affected vascular density reduction in POAG patients.

Impact of Acute Short-term Hypobaric Hypoxia on Anterior Chamber Geometry

Précis: Hypobaric hypoxia, the major environmental factor at high altitudes, has been observed to induce pupil miosis and widening of the anterior chamber angle. This environment may be safe for individuals with narrow angle and deserves further study. Purpose: This study aimed to quantify anterior chamber biometric parameters before and after acute short-term, effortless exposure to hypobaric hypoxia (HH) in healthy lowlanders using swept-source anterior segment optical coherence tomography (SS AS-OCT). Methods: This prospective study included 25 healthy young lowlanders (50 eyes) who underwent SS AS-OCT measurements and intraocular pressure (IOP) assessments under baseline sea-level conditions (T1).They were then passively exposed to simulated 4000 m above sea level for 3 hours and underwent Acute mountain sickness (AMS) symptoms evaluation and IOP measurement after 2-hours exposure to HH (T2).Repeat SS AS-OCT measurements and IOP assessments were taken within 15 minutes after leaving the hypobaric chamber (T3). Anterior segment parameters including anterior chamber depth (ACD),lens vault (LV),angle opening distance (AOD500), trabecular-iris space area (TISA500), angle recess area (ARA500) at 500 μm from the scleral spur, iris curvature (IC), iris volume (IV), pupil diameter (PD), and central corneal thickness (CCT) were obtained through SS AS-OCT. These repeated measurements were compared using linear mixed model analysis. Results: In comparison to sea level, both IOP (16.4±3.4 vs. 14.9±2.4 mm Hg, P=0.029) and PD (5.36±0.77 vs. 4.78±0.89 mm, P=0.001) significantly decreased after exposure to HH. Significant post-HH changes (Mean difference (95% CI)) were observed in AOD500 (0.129 (0.006, 0.252), P=0.04), TISA500 (0.059 (0.008, 0.11), P=0.025), ARA500 (0.074 (0.008, 0.141), P=0.029), IV (1.623 (0.092, 3.154), P=0.038), and IC (−0.073 (−0.146, 0.001), P=0.047), while CCT, ACD, and LV remained stable. After adjusting for age, post-HH variations in AOD500 (Beta=0.553, 95% CI: 0.001, 1.105, P=0.048) and TISA500 (Beta=0.256, 95% CI: 0.02, 0.492, P=0.034) were associated with decreased IC but were not related to lowered arterial oxygen pressure or IV increase per millimeter of pupil miosis (IV/PD). These differences in anterior segment parameters were neither correlated with differences in IOP nor AMS. Conclusion: After short-term, effortless exposure to hypobaric hypoxia, pupil miosis occurred with widening of the anterior chamber angle and decreased IC. These changes in anterior chamber angle parameters were associated with decreased IC but did not correlate with the post-hypobaric variations in IV/PD, IOP, or AMS.

The impact of different postures on acute intraocular pressure and accommodation responses during reading

IntroductionTo investigate the effects of different reading postures on intraocular pressure (IOP) and near-work-induced transient myopia (NITM) in children with myopia.MethodsSixty myopic children were instructed to read a book text placed at 33 cm for 30 min with two different reading postures: head bowed and head upright postures. The participants’ IOP and NITM were assessed using a rebound tonometer and an open-field autorefractor. The measurement of IOP was conducted prior to reading, during reading sessions (at 5, 10, 20, and 30-min intervals), and after a 5-min recovery period.ResultsFor the head bowed posture, the mean baseline IOP was 16.13 ± 2.47 mmHg. A significant rise in IOP was observed after 5 min of reading (17.17 ± 2.97 mmHg; +1.03 ± 2.29 mmHg; p = 0.014). Subsequent measurements revealed a further increase after 20 min (17.87 ± 2.90 mmHg; +1.73 ± 2.58 mmHg; p < 0.001), which continued to persist even after 30 min of reading (17.57 ± 3.46 mmHg; +1.43 ± 2.66 mmHg; p = 0.002). The IOP at different time points measured in the head upright posture did not show any significant difference in comparison to the baseline measurement (all p = 1.000). Compared to reading with the head upright, reading with the head bowed resulted in a greater increase in IOP at each time point (p < 0.05). Furthermore, the NITM was higher for reading with the head bowed than for reading with head upright at 30 min (-0.24 ± 0.53 D vs. -0.12 ± 0.47 D, p = 0.038).ConclusionReading in a head bowed position resulted in greater increases in IOP and NITM compared to reading in a head upright posture.

Moxifloxacin-associated acute pigment dispersion and iris transillumination after phakic lens surgery

Introduction: Acute pigment dispersion and elevated intraocular pressure (IOP) were found after phakic intraocular lens surgery where 0.5% moxifloxacin was used. While scattered reports can be found in the literature, to the authors' knowledge, this is the first time it has been linked to intracameral 0.5% moxifloxacin. Patient and Clinical Findings: A 23-year-old man experienced symptoms of unilateral eye pain, increased IOP, diffuse pigment dispersion, transillumination defects, and mydriasis after successful bilateral Starr Visian EVO implantable collamer lens implantation. Diagnosis, Intervention and Outcomes: Intracameral moxifloxacin (0.5%) was given at the time of the procedure and was suspected to be the cause of this patient's postoperative findings. These findings are consistent with iris toxicity associated with systemic moxifloxacin. Supportive care was given, however, the resulting pigment dispersion and mydriasis are permanent. Conclusions: Although generally safe for intracameral use, moxifloxacin has the potential to be toxic to the iris. Patients with phakia may be at higher risk of this toxicity, and lower concentrations of intracameral moxifloxacin should be considered in these patients.

Antioxidant effect of gallic acid on retinal ganglion cells in glaucoma model

To evaluate the protective effect of gallic acid on the optic nerve by studying the inhibitory effect of gallic acid on oxidative stress in retinal ganglion cells. 100 male SD rats were randomly divided into four groups: normal control group, simple high IOP group, 0.5% gallic acid experimental group, and 1% gallic acid experimental group. HE staining, immunofluorescence, DHE staining, Western blot, and q-PCR were used to observe the antioxidant effect of gallic acid on the retina of acute ocular hypertension rats. HE staining of the retina of SD rats confirmed that the nucleus of RGCs was clear, the thickness of the RNFL was regular in the normal control group, and the nucleus of RGCs was ruptured and lysed in the simple high intraocular pressure (IOP) group and the gallic acid group, and the thickness of the RNFL was significantly thickened, but the thickness of the RNFL in the gallic acid group was significantly reduced compared with that in the simple high IOP group (p < 0.05). DHE staining showed that ROS content in the simple high IOP group was significantly increased compared with the normal control group, and ROS content was significantly decreased after the application of gallic acid (p < 0.05). Immunofluorescence staining with Brn-3a antibody confirmed that the number of RGCs was significantly reduced in the simple high IOP group compared with the normal control group, whereas after application of gallic acid, the number of RGCs was significantly more in the gallic acid group than in the simple high IOP group (p < 0.05). Western Blot and q-PCR confirmed that hypoxia-inducing factor 1α (HIF-1α) protein content and transcription level were significantly increased in the retinal tissue of the simple high IOP group, and gallic acid could inhibit HIF-1α protein content (p < 0.05) and reduce transcription factor level (p < 0.05). Gallic acid exerts a protective effect on RGC by inhibiting oxidative stress in rats with acute IOP elevation.

Geniposide Attenuates Oxygen-glucose Deprivation/Recovery-induced Retinal Ganglion Cell Injury via Akt/Nrf-2 Signaling Pathway.

Glaucoma is an eye disease. Its pathological process involves retinal ischemia-reperfusion (I/R), which causes irreversible blindness in patients. Geniposide (Gen), a bioactive iridoid glycoside extracted from the fruit of gardenia, exhibits many biological effects, such as anti-oxidative stress, anti-inflammation, anti-apoptosis, anti-endoplasmic reticulum stress, and anti-thrombotic effects. However, its therapeutic potential for the retinal I/R injury remains unclear. This study investigated the protective effect of Gen against I/R injury by inhibiting abnormal reactive oxygen species (ROS) and retinal neuron apoptosis. We used oxygen-glucose deprivation/reoxygenation (OGD/R) to induce R28 cells to mimic the pathological process of I/R in glaucoma. We conducted CCK-8 analysis and TUNEL staining to examine cell proliferation and apoptosis in glaucoma. Western blotting was used to assay the expressions of apoptosis and Akt/Nrf-2 pathway-related proteins. The production of ROS was detected by using the corresponding kit. Cell viability decreased, whereas TUNEL staining-positive cells and ROS production increased after the OGD/R injury. The contents of cleaved caspase-3 and Bax/Bcl-2 increased after the OGD/R injury. Treatment with 200 μM of Gen effectively improved the cell viability and suppressed cell apoptosis and ROS production. In addition, Gen could significantly promote the activation of the Akt/Nrf-2 signaling pathway in R28 cells, which was blocked by the inhibition of Akt/Nrf-2. We in vivo verified the neuroprotective effect of Gen by establishing an acute high intraocular pressure (aHIOP) model and obtained similar results to those of the in vitro experimental results. Hence, it can be suggested that Gen provides neuroprotection against the OGD/R-induced injury of R28 cells by activating the Akt/Nrf-2 signaling pathway, which is beneficial for the clinical treatment of glaucoma.

Prophylaxis against intraocular pressure spikes following uncomplicated phacoemulsification: a systematic-review and meta-analysis.

To investigate the effect of perioperative intraocular pressure (IOP) lowering medications on controlling postoperative IOP following uncomplicated phacoemulsification. Ovid MEDLINE, EMBASE, and Cochrane CENTRAL databases were searched up until November 2022. Randomised controlled trials (RCTs) that assessed IOP change via applanation tonometry in medicated and control arms following uncomplicated cataract surgery in healthy eyes were included. The primary outcome was the weighted mean difference (WMD) of IOP at 2-8 h, 12-24 h, and 1-7 days postoperatively within each medication class or common fixed-combination formulations. Risk of bias was assessed using the revised risk of bias in randomised trials (RoB-2). Level of evidence was rated using theGrading of Recommendation, Assessment, Development and Evaluation (GRADE) RESULTS: From 702 screened articles, 30 RCTs involving 2986 eyes were included. There was a statistically significant reduction in IOP favouring treatment arms at 2-8 h (WMD = -3.87 mmHg; 95% CI [-4.75, -3.00]; p < 0.001) and 12-24 h (WMD = -2.69 mmHg; 95% CI [-3.36, -2.02]; p < 0.001), with the effect wearing off beyond 1 day (p = 0.18). Between medication classes, the largest effect at both 2-8 h and 12-24 h was observed with intracameral cholinergics or fixed-combination carbonic anhydrase inhibitor-beta-blocker (FCCB) formulations. Conversely, the smallest effect was observed with prostaglandin analogues, alpha-agonists, and topical carbonic anhydrase inhibitors (CAIs). Prophylaxis against acute IOP elevations following uncomplicated cataract surgery is effective. FCCB and intracameral cholinergics are the most effective ocular antihypertensive agents, while alpha-agonists, prostaglandin analogues, and topical CAIs were found to be the least effective. These findings may inform future surgical guidelines.

Chitosan-Rapamycin Carbon Dots Alleviate Glaucomatous Retinal Injury by Inducing Autophagy to Promote M2 Microglial Polarization.

Glaucoma is a prevalent cause of irreversible vision impairment, characterized by progressive retinal ganglion cells (RGCs) loss, with no currently available effective treatment. Rapamycin (RAPA), an autophagy inducer, has been reported to treat glaucoma in rodent models by promoting RGC survival, but its limited water solubility, systemic toxicity, and pre-treatment requirements hinder its potential clinical applications. Chitosan (CS)-RAPA carbon dot (CRCD) was synthesized via hydrothermal carbonization of CS and RAPA and characterized by transmission electron microscopy, Fourier transform infrared spectra, and proton nuclear magnetic resonance. In vitro assays on human umbilical cord vein endothelial and rat retinal cell line examined its biocompatibility and anti-oxidative capabilities, while lipopolysaccharide-stimulated murine microglia (BV2) assays measured its effects on microglial polarization. In vivo, using a mouse retinal ischemia/reperfusion (I/R) model by acute intraocular pressure elevation, the effects of CRCD on visual function, RGC apoptosis, oxidative stress, and M2 microglial polarization were examined. CRCD exhibited good water solubility and anti-oxidative capabilities, in the form of free radical scavenging. In vitro, CRCD was bio-compatible and lowered oxidative stress, which was also found in vivo in the retinal I/R model. Additionally, both in vitro with lipopolysaccharide-stimulated BV2 cells and in vivo with the I/R model, CRCD was able to promote M2 microglial polarization by activating autophagy, which, in turn, down-regulated pro-inflammatory cytokines, such as IL-1β and TNF-α, as well as up-regulated anti-inflammatory cytokines, such as IL-4 and TGF-β. All these anti-oxidative and anti-inflammatory effects ultimately aided in preserving RGCs, and subsequently, improved visual function. CRCD could serve as a potential novel treatment strategy for glaucoma, via incorporating RAPA into CDs, in turn not only mitigating its toxic side effects but also enhancing its therapeutic efficacy.

Displacement of the Lamina Cribrosa With Acute Intraocular Pressure Increase in Brain-Dead Organ Donors.

To examine deformations of the optic nerve head (ONH) deep tissues in response to acute elevation of intraocular pressure (IOP). Research-consented brain-dead organ donors underwent imaging by spectral domain optical coherence tomography (OCT). OCT imaging was repeated while the eye was sequentially maintained at manometric pressures of 10, 30, and 50mm Hg. Radial scans of the ONH were automatically segmented by deep learning and quantified in three dimensions by a custom algorithm. Change in lamina cribrosa (LC) depth and choroidal thickness was correlated with IOP and age by linear mixed-effect models. LC depth was computed against commonly utilized reference planes. Twenty-six eyes from 20 brain-dead organ donors (age range, 22-62years; median age, 43years) were imaged and quantified. LC depth measured against a reference plane based on Bruch's membrane (BM), BM opening, and an anterior sclera canal opening plane showed both a reduction and an increase in LC depth with IOP elevation. LC depth universally increased in depth when measured against a sclera reference plane. Choroidal (-0.5222µm/mm Hg, P < 0.001) and retinal nerve fiber layer thickness (-0.0717µm/mm Hg, P < 0.001) significantly thinned with increasing IOP. The magnitude of LC depth change with IOP was significantly smaller with increasing age (P < 0.03 for all reference planes). LC depth changes with IOP reduce with age and are significantly affected by the reference plane of choice, which highlights a need for standardizing LC metrics to properly follow progressive remodeling of the loadbearing tissues of the ONH by OCT imaging and for the definition of a reference database.

Single-cell RNA sequencing analysis of the retina under acute high intraocular pressure.

JOURNAL/nrgr/04.03/01300535-202419110-00032/figure1/v/2024-03-08T184507Z/r/image-tiff High intraocular pressure causes retinal ganglion cell injury in primary and secondary glaucoma diseases, yet the molecular landscape characteristics of retinal cells under high intraocular pressure remain unknown. Rat models of acute hypertension ocular pressure were established by injection of cross-linked hyaluronic acid hydrogel (Healaflow®). Single-cell RNA sequencing was then used to describe the cellular composition and molecular profile of the retina following high intraocular pressure. Our results identified a total of 12 cell types, namely retinal pigment epithelial cells, rod-photoreceptor cells, bipolar cells, Müller cells, microglia, cone-photoreceptor cells, retinal ganglion cells, endothelial cells, retinal progenitor cells, oligodendrocytes, pericytes, and fibroblasts. The single-cell RNA sequencing analysis of the retina under acute high intraocular pressure revealed obvious changes in the proportions of various retinal cells, with ganglion cells decreased by 23%. Hematoxylin and eosin staining and TUNEL staining confirmed the damage to retinal ganglion cells under high intraocular pressure. We extracted data from retinal ganglion cells and analyzed the retinal ganglion cell cluster with the most distinct expression. We found upregulation of the B3gat2 gene, which is associated with neuronal migration and adhesion, and downregulation of the Tsc22d gene, which participates in inhibition of inflammation. This study is the first to reveal molecular changes and intercellular interactions in the retina under high intraocular pressure. These data contribute to understanding of the molecular mechanism of retinal injury induced by high intraocular pressure and will benefit the development of novel therapies.

Immediate effect of anti-VEGF injections on optic nerve head: Correlation between intraocular pressure and anatomical peripapillary changes.

This study was designed to investigate retinal nerve fiber layer (RNFL) and radial peripapillary capillaries (RPC) changes on optical coherence tomography (OCT) angiography and OCT thickness alterations associated with acutely increased intraocular pressure after intravitreal injections. This observational clinical study was conducted on 35 eyes (35 patients) with treatment-naïve age-related macular degeneration (AMD) and type 1 or type 2 MNV were enrolled. All patients underwent anti-vascular endothelial grow factor (VEGF) intravitreal injections with 0.05-mL aflibercept (2 mg) between January 2022 and October 2022. Peripapillary OCT angiography perfusion density, retinal nerve fiber layer thickness, and intraocular pressure (IOP) were measured before and immediately after intravitreal injections. In particular, the analysis was performed at the following visits: (T0) 5 to 15 min before the injection of aflibercept; (T1) 2 to 5 min after the injection of aflibercept. Paired t-test was used to compare pre-injection and post-injection values. The mean baseline IOP (T0) value was 17.26 ± 2.4 mmHg and the immediate post-injection IOP (T1) mean value was 34.7 ± 11.50 mmHg (P < 0.01). The mean global RNFL thickness before and immediately after the injection was 100.9 ± 18.8 m and 98.6 ± 17.4 m (P = 0.001). Furthermore, the topographical RNFL analysis showed significant thickness reduction of the nasal and inferior sectors after the procedure when compared to T0 (P = 0.046 and P = 0.001). On the contrary, the mean RCP density changes at T1 did not reach statistically significant (P = 0.636). Furthermore, we found a significant negative correlation between the retinal nerve fiber layer global thickness and the IOP changes (Pearson's correlation = -0.126; P = 0.031). In particular, the nasal RNFL region showed a significant negative correlations with IOP values (Pearson's correlation = -0.198, P = 0,046). We reported acute IOP changes that are associated with reduced RNFL thickness in a group of patients undergoing intravitreal injections of anti-VEGF drugs for neovascular age-related macular degeneration. Moreover, topographical sub-analysis revealed that the nasal RNFL region is most prone to IOP fluctuations. This finding may explain the sudden visual acuity change in patients immediately after injection and may sustain injuries to optic nerve head structures producing glaucomatous damage.

Casein kinase-2 inhibition promotes retinal ganglion cell survival after acute intraocular pressure elevation.

Intraocular pressure elevation can induce retinal ganglion cell death and is a clinically reversible risk factor for glaucoma, the leading cause of irreversible blindness. We previously demonstrated that casein kinase-2 inhibition can promote retinal ganglion cell survival and axonal regeneration in rats after optic nerve injury. To investigate the underlying mechanism, in the current study we increased the intraocular pressure of adult rats to 75 mmHg for 2 hours and then administered a casein kinase-2 inhibitor (4,5,6,7-tetrabromo-2-azabenzimidazole or 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole) by intravitreal injection. We found that intravitreal injection of 4,5,6,7-tetrabromo-2-azabenzimidazole or 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole promoted retinal ganglion cell survival and reduced the number of infiltrating macrophages. Transcriptomic analysis showed that the mitogen activated protein kinase signaling pathway was involved in the response to intraocular pressure elevation but was not modulated by the casein kinase-2 inhibitors. Furthermore, casein kinase-2 inhibition downregulated the expression of genes (Cck, Htrsa, Nef1, Htrlb, Prph, Chat, Slc18a3, Slc5a7, Scn1b, Crybb2, Tsga10ip, and Vstm21) involved in intraocular pressure elevation. Our data indicate that inhibition of casein kinase-2 can enhance retinal ganglion cell survival in rats after acute intraocular pressure elevation via macrophage inactivation.

Risk Factors for Flat Anterior Chamber Requiring Intervention After Glaucoma Drainage Implant: A Retrospective Case-Controlled Study

To identify risk factors for flat anterior chamber that required additional intervention in the postoperative period (90 days) after uncomplicated Baerveldt Glaucoma Implant (BGI) surgery. Retrospective, matched case-control study. A total of 42 cases (eyes) that received BGI at Anne Bates Leach Eye Hospital between February 1, 2011, and January 1, 2019, and that developed flat anterior chamber were included. For each case, we matched 2 controls (84). Variables included sex, diagnosis, diabetes, hypertension, pre- and postoperative glaucoma medications, ocular conditions, and intraocular pressure (IOP). Multivariable conditional logistic regression determined odds ratios (ORs) for independent predictors. Case patients were more likely to be female (69.1% case patients/41.7% controls), to have a history of taking oral carbonic anhydrase inhibitors (CAIs) at tube opening (21.4%/7.1%), to be of another race/ethnicity (11.9%/0.0%), and to have pseudoexfoliation (23.8%/6.0%), and were less likely to be using cholinergic agonists (0.0%/11.9%) at baseline and to have primary open angle glaucoma (42.9%/64.3%). Case patients had greater mean age (75.9/64.9 years), earlier tube opening time (5.6/6.2 weeks), and lower IOP after tube opening (7.2/14.4 mm Hg), but IOP before opening was higher (24.7/19.5 mm Hg). We identified 3 independent predictors: older age (10-year increase OR=3.59, P < .0001), oral CAI use at tube opening (OR=5.65, P=.009), and higher IOP prior to tube opening (3 mm Hg increase OR=1.30, P=.018). Risk factors for flat anterior chamber were older age, oral CAIs at tube opening, and higher IOP before tube opening. Strategies to minimize the acute IOP reduction that preceded this complication such as discontinuing oral CAI prior to tube opening may be considered.

How Myopia and Glaucoma Influence the Biomechanical Susceptibility of the Optic Nerve Head.

The purpose of this study was to assess optic nerve head (ONH) deformations following acute intraocular pressure (IOP) elevations and horizontal eye movements in control eyes, highly myopic (HM) eyes, HM eyes with glaucoma (HMG), and eyes with pathologic myopia (PM) alone or PM with staphyloma (PM+S). We studied 282 eyes, comprising of 99 controls (between +2.75 and -2.75 diopters), 51 HM (< -5 diopters), 35 HMG, 21 PM, and 75 PM+S eyes. For each eye, we imaged the ONH using spectral-domain optical coherence tomography (OCT) under the following conditions: (1) primary gaze, (2) 20 degrees adduction, (3) 20 degrees abduction, and (4) primary gaze with acute IOP elevation (to ∼35 mm Hg) achieved through ophthalmodynamometry. We then computed IOP- and gaze-induced ONH displacements and effective strains. Effective strains were compared across groups. Under IOP elevation, we found that HM eyes exhibited significantly lower strains (3.9 ± 2.4%) than PM eyes (6.9 ± 5.0%, P < 0.001), HMG eyes (4.7 ± 1.8%, P = 0.04), and PM+S eyes (7.0 ± 5.2%, P < 0.001). Under adduction, we found that HM eyes exhibited significantly lower strains (4.8% ± 2.7%) than PM+S eyes (6.0 ± 3.1%, P = 0.02). We also found that eyes with higher axial length were associated with higher strains. Our study revealed that eyes with HMG experienced significantly greater strains under IOP compared to eyes with HM. Furthermore, eyes with PM+S had the highest strains on the ONH of all groups.

Age-related deficits in retinal autophagy following intraocular pressure elevation in autophagy reporter mouse model

This study quantified age-related changes to retinal autophagy using the CAG-RFP-EGFP-LC3 autophagy reporter mice and considered how aging impacts autophagic responses to acute intraocular pressure (IOP) stress. IOP was elevated to 50 mm Hg for 30 minutes in 3-month-old and 12-month-old CAG-RFP-EGFP-LC3 (n = 7 per age group) and Thy1-YFPh transgenic mice (n = 3 per age group). Compared with younger eyes, older eyes showed diminished basal autophagy in the outer retina, while the inner retina was unaffected. Autophagic flux (red:yellow puncta ratio) was elevated in the inner plexiform layer. Three days following IOP elevation, older eyes showed poorer functional recovery, most notably in ganglion cell responses compared to younger eyes (12 months old: −33.4 ± 5.3% vs. 3 months mice: −13.4 ± 4.5%). This paralleled a reduced capacity to upregulate autophagic puncta volume in the inner retina in older eyes, a response that was seen in younger eyes. Age-related decline in basal and stress-induced autophagy in the retina is associated with greater retinal ganglion cells' susceptibility to IOP elevation.

Clinical Features Associated with Acute Elevated Intraocular Pressure After Intravitreal Anti-VEGF Injections.

To study the effects of intravitreal injection (IVI) of anti-VEGF (vascular endothelial growth factor) agents on intraocular pressure (IOP) and find associations with acute pressure spikes. This was a three-month, prospective study of patients receiving outpatient IVI of anti-VEGF agents for diabetic retinopathy (DR), age-related macular degeneration (AMD), and retinal vein occlusion (RVO) at the Acuity Eye Group Medical Centers. IOP was measured pre- and post-injection at 10-minute intervals up to 50 minutes after injection with a handheld tonometer. Patients with an IOP greater than 35 mmHg at 30 minutes received an anterior chamber paracentesis (ACP), while patients below 35 mmHg were monitored without intervention. A total of 617 patients (51% female, 49% male) received IVI for DR (n = 199), AMD (n = 355), and RVO (n = 63). ACP was performed in 17 patients. Average pre-injection IOP was 16 ± 4 compared to 24 ± 7 mmHg for the non-ACP vs ACP group, respectively (mean ± standard deviation), p < 0.0001. IOP returned to baseline in 98% of patients at 50 minutes. A diagnosis of glaucoma and glaucoma suspect was more prevalent in the ACP group compared to the non-ACP group, 82.3% vs 14.2% and 17.6% vs 9.0%, respectively, p < 0.0001 and p > 0.05. Patients with a pre-injection IOP >25 mmHg and a history of glaucoma had a 58.3% rate of ACP. A 31-gauge needle had a higher mean increase in IOP from baseline compared to 30-gauge needle, p < 0.0001. IOP spikes are most significant in the first 10 minutes after IVI but typically resolve within the first hour. However, utilizing a smaller 31-gauge IVI in patients with a glaucoma history and pre-injection IOP >25 mmHg may be associated with significant IOP spikes lasting longer than 30 minutes.

In vivo noninvasive mitochondrial redox assessment of the optic nerve head to predict disease.

Eye diseases are diagnosed by visualizing often irreversible structural changes occurring late in disease progression, such as retinal ganglion cell loss in glaucoma. The retina and optic nerve head have high mitochondrial energy need. Early mitochondrial/energetics dysfunction may predict vulnerability to permanent structural changes. In the in vivo murine eye, we used light-based resonance Raman spectroscopy (RRS) to assess noninvasively the redox states of mitochondria and hemoglobin which reflect availability of electron donors (fuel) and acceptors (oxygen). As proof of principle, we demonstrated that the mitochondrial redox state at the optic nerve head correlates with later retinal ganglion loss after acute intraocular pressure (IOP) elevation. This technology can potentially map the metabolic health of eye tissue in vivo complementary to optical coherence tomography, defining structural changes. Early detection (and normalization) of mitochondrial dysfunction before irreversible damage could lead to prevention of permanent neural loss.

Acute and subacute intraocular pressure and macular microvascular structure changes after intravitreal ranibizumab injection in eyes with branch retinal vein occlusion

PurposeTo investigate early changes in the intraocular pressure (IOP) and macular microvascular structure in eyes with branch retinal vein occlusion (BRVO) treated with intravitreal Ranibizumab injection.MethodsThis study enrolled 30 patients (one eye per patient) who received intravitreal injections (IVI) of ranibizumab for macular edema secondary to BRVO. IOP were measured before, 30 min (min) and 1 month following IVI. Changes in macular microvascular structure were examined via assessment of foveal avascular zone (FAZ) parameters, vascular density (VD) of superficial vascular complex (SVC), and deep vascular complex (DVC) in whole macula, central fovea and parafovea area which were measured automatically by optical coherence tomography angiography (OCTA) on the same time as IOP examinations. Paired t test and Wilcoxon test were used to compare pre- and post-injection values. The correlation between IOP and OCTA findings was assessed.ResultsIOP Measurements at 30 min post-IVI (17.91 ± 3.36 mmHg) increased significantly from baseline (15.07 ± 2.58 mmHg, p < 0.001), then became similar with baseline after 1 month (15.00 ± 3.16 mmHg, p = 0.925). 30 min past the injection, the parameters of VD of the SCP significantly decreased in comparison to baseline, then became similar with baseline after one month, while there were no significant changes in other OCTA parameters, including parameters of VD of the DCP and the FAZ. At 1 month after IVI, in comparison to baseline, no significant changes were observed in all of the OCTA parameters (P > 0.05). There were no significant correlations between IOP and OCTA findings no matter 30 min or 1 month post-IVI (P > 0.05).ConclusionsTransient IOP elevation and decreased superficial macular capillary perfusion density were detected 30 min post-IVI, however, no potential continual macular microvascular damage was suspected.

Adduction induces large optic nerve head deformations in subjects with normal-tension glaucoma

PurposeTo assess intraocular pressure (IOP)-induced and gaze-induced optic nerve head (ONH) strains in subjects with high-tension glaucoma (HTG) and normal-tension glaucoma (NTG).DesignClinic-based cross-sectional study.MethodsThe ONH from one eye of 228...

An unusual presentation of Urrets-Zavalia syndrome after minimally invasive glaucoma surgery in a case of pigmentary glaucoma

Urrets-Zavalia syndrome (UZS) is a rare post-operative condition characterized by a fixed and dilated pupil after ophthalmic surgery. UZS syndrome was first appreciated by Castroviejo and was later published in 1963 by Alberto Urrets-Zavalia in patients who underwent penetrating keratoplasty (PKP). Though there are many risk factors for UZS, the most widely accepted theories are ischemia of the iris and acute rise in intraocular pressure (IOP), with possible spontaneous partial recovery expected in some of them. Contrastingly, permanent UZS was also rarely reported in the literature by Mocan et al. among the pigment dispersion syndrome (PDS) population. In this manuscript, we have reported an unusual presentation of UZS after iStent implantation (Glaukos Corporation, United States) with the following two possible risk factors, namely, acute post-operative IOP spike and pre-existing pigmentary dispersion syndrome condition, which, accordingly to our knowledge, has never been reported in the literature before.