Acute Intraocular Pressure Elevation Research Articles

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.

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.

The arginase 1/ornithine decarboxylase pathway suppresses HDAC3 to ameliorate the myeloid cell inflammatory response: implications for retinal ischemic injury

The enzyme arginase 1 (A1) hydrolyzes the amino acid arginine to form L-ornithine and urea. Ornithine is further converted to polyamines by the ornithine decarboxylase (ODC) enzyme. We previously reported that deletion of myeloid A1 in mice exacerbates retinal damage after ischemia/reperfusion (IR) injury. Furthermore, treatment with A1 protects against retinal IR injury in wild-type mice. PEG-A1 also mitigates the exaggerated inflammatory response of A1 knockout (KO) macrophages in vitro. Here, we sought to identify the anti-inflammatory pathway that confers macrophage A1-mediated protection against retinal IR injury. Acute elevation of intraocular pressure was used to induce retinal IR injury in mice. A multiplex cytokine assay revealed a marked increase in the inflammatory cytokines interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) in the retina at day 5 after IR injury. In vitro, blocking the A1/ODC pathway augmented IL-1β and TNF-α production in stimulated macrophages. Furthermore, A1 treatment attenuated the stimulated macrophage metabolic switch to a pro-inflammatory glycolytic phenotype, whereas A1 deletion had the opposite effect. Screening for histone deacetylases (HDACs) which play a role in macrophage inflammatory response showed that A1 deletion or ODC inhibition increased the expression of HDAC3. We further showed the involvement of HDAC3 in the upregulation of TNF-α but not IL-1β in stimulated macrophages deficient in the A1/ODC pathway. Investigating HDAC3 KO macrophages showed a reduced inflammatory response and a less glycolytic phenotype upon stimulation. In vivo, HDAC3 co-localized with microglia/macrophages at day 2 after IR in WT retinas and was further increased in A1-deficient retinas. Collectively, our data provide initial evidence that A1 exerts its anti-inflammatory effect in macrophages via ODC-mediated suppression of HDAC3 and IL-1β. Collectively we propose that interventions that augment the A1/ODC pathway and inhibit HDAC3 may confer therapeutic benefits for the treatment of retinal ischemic diseases.

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.

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.

RAGE and its ligand amyloid beta promote retinal ganglion cell loss following ischemia-reperfusion injury.

Glaucoma is a progressive neurodegenerative disease associated with age. Accumulation of amyloid-beta (Aß) proteins in the ganglion cell layer (GCL) and subsequent retinal ganglion cell (RGC) loss is an established pathological hallmark of the disease. The mechanism through which Aß provokes RGC loss remains unclear. The receptor for the advanced glycation end product (RAGE), and its ligand Aß, have been shown to mediate neuronal loss via internalizing Aß within the neurons. In this study, we investigated whether the RAGE-Aß axis plays a role in RGC loss in experimental glaucoma. Retinal ischemia was induced by an acute elevation of intraocular pressure in RAGE-/- and wild-type (WT) control mice. In a subset of animals, oligomeric Aß was injected directly into the vitreous of both strains. RGC loss was assessed using histology and biochemical assays. Baseline and terminal positive scotopic threshold (pSTR) were also recorded. Retinal ischemia resulted in 1.9-fold higher RGC loss in WT mice compared to RAGE-/- mice (36 ± 3% p < 0.0001 vs. 19 ± 2%, p = 0.004). Intravitreal injection of oligomeric Aß resulted in 2.3-fold greater RGC loss in WT mice compared to RAGE-/- mice, 7-days post-injection (55 ± 4% p = 0.008 vs. 24 ± 2%, p = 0.02). We also found a significant decline in the positive scotopic threshold response (pSTR) amplitude of WT mice compared to RAGE-/- (36 ± 3% vs. 16 ± 6%). RAGE-/- mice are protected against RGC loss following retinal ischemia. Intravitreal injection of oligomeric Aß accelerated RGC loss in WT mice but not RAGE-/-. A co-localization of RAGE and Aß, suggests that RAGE-Aß binding may contribute to RGC loss.

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...

Spontaneous Hyphema and Vitreous Hemorrhage Causing Secondary Glaucoma in a Patient on Apixaban

Background: Spontaneous hyphema is the rare occurrence of hemorrhage within the anterior chamber of the eye without a predisposing traumatic event. Hyphema can be associated with acute elevations in intraocular pressure in up to 30% of cases, which poses a significant risk for permanent vision loss if not quickly recognized and treated in the emergency department (ED). Anticoagulant and antiplatelet medications have been previously associated with cases of spontaneous hyphema; however, there are limited reports of hyphema with associated acute glaucoma in a patient taking a direct oral anticoagulant. Due to the limited data of reversal therapies for direct oral anticoagulants in intraocular hemorrhage, these patients pose a challenge in deciding whether to reverse anticoagulation in the ED.Case Report: We present a case of a 79-year-old man on apixaban anticoagulation therapy who presented to the ED with spontaneous painful vision loss in the right eye with associated hyphema. Point-of-care ultrasound revealed an associated vitreous hemorrhage, and tonometry was significant for acute glaucoma. As a result, the decision was made to reverse the patient's anticoagulation with four-factor activated prothrombin complex concentrate.Why Should an Emergency Physician Be Aware of This? This case is an example of acute secondary glaucoma due to a hyphema and vitreous hemorrhage. There is limited evidence regarding anticoagulation reversal in this setting. A second site of bleeding was identified by utilization of point-of-care ultrasound, which led to the diagnosis of a vitreous hemorrhage. This allowed for shared decision-making between the emergency physician, ophthalmologist, and patient regarding the risks and potential benefits of the reversal of anticoagulation. Ultimately, the patient decided to have his anticoagulation reversed to try and preserve vision.

Fibrin Membrane Induced Pupillary Block Glaucoma Treated With Nd:YAG Laser After Uncomplicated Cataract Surgery

Background: Fibrin pupillary-block glaucoma is a rare complication after uneventful cataract surgery. We aimed to share our treatment approach with Nd: YAG laser fibrin membranotomy.&#x0D; &#x0D; Case presentation: A 68-year-old male patient without any systemic comorbidity developed acute intraocular pressure elevation with a shallow anterior chamber 7 days after uneventful cataract surgery. Visual acuity (VA) of the right eye was 0.1 and IOP was 48 mmHg. There was a fibrin membrane that completely closed the pupillary space. It was observed that there was 360-degree iridocorneal contact in the periphery. An Nd: YAG laser was applied to create an opening at the upper edge of the fibrin membrane. A rapid deepening of the anterior chamber was observed immediately after perforation of the membrane. After deepening of the anterior chamber, permanent peripheral iridotomy was opened with argon-Nd: YAG.&#x0D; &#x0D; Conclusion: Although the fibrin membrane is seen after uneventful cataract surgeries usually suggests which inflammation is triggered, these results can sometimes occur even before the disease is present.

AI-based clinical assessment of optic nerve head robustness superseding biomechanical testing

Background/aimsTo use artificial intelligence (AI) to: (1) exploit biomechanical knowledge of the optic nerve head (ONH) from a relatively large population; (2) assess ONH robustness (ie, sensitivity of the ONH...

Mechanisms of retinal ganglion cell injury following acute increases in intraocular pressure

The maintenance of intraocular pressure (IOP) is critical to preserving the pristine optics required for vision. Disturbances in IOP can directly impact the optic nerve and retina, and inner retinal injury can occur following acute and chronic IOP elevation. There are a variety of animal models that have been developed to study the effects of acute and chronic elevation of IOP on the retina, retinal ganglion cell (RGC) morphology, intracellular signaling, gene expression changes, and survival. Acute IOP models induce injury that allows for the study of RGC response to well characterized injury and potential recovery. This review will focus on the initial impact of acute IOP elevation on RGC injury and recovery as these early responses may be the best targets for potential therapeutic interventions to promote RGC survival in glaucoma.

High Levels of Heat Shock Protein 47 in the Aqueous Humor of Patients with Acute Primary Angle Closure

Introduction: Acute primary angle closure (APAC) is often characterized by acute elevation of intraocular pressure accompanied by severe ocular and systemic symptoms. Excessive collagen accumulation, which can be caused by upregulated heat shock protein 47 (HSP47) expression, can produce scarring in rat conjunctival blebs. Meanwhile, the presence of HSP47 in human aqueous humor and its levels are yet to be determined. Methods: We examined 32 consecutive patients with APAC and 16 age-matched participants without APAC scheduled for cataract surgery who were enrolled as a control group. Aqueous humor samples were collected from all subjects at the time of surgery and compared between the subjects with and without APAC. Results: The levels of HSP47 in the aqueous humor of patients with APAC (1,210.4 ± 450.2 pg/mL) were found to be significantly increased (p = 0.001) compared with those in the control group (863.4 ± 240.0 pg/mL). Notably, the levels of HSP47 negatively correlated with the age of patients with APAC (p = 0.023). Conclusion: HSP47 was upregulated in the aqueous humor of patients with APAC and may play a role in scarring after trabeculectomy for APAC.

Mitochondrial Dysfunction in a High Intraocular Pressure-Induced Retinal Ischemia Minipig Model.

Purpose: Retinal ischemia (RI) and progressive neuronal death are sight-threatening conditions. Mitochondrial (mt) dysfunction and fusion/fission processes have been suggested to play a role in the pathophysiology of RI. This study focuses on changes in the mt parameters of the neuroretina, retinal pigment epithelium (RPE) and choroid in a porcine high intraocular pressure (IOP)-induced RI minipig model. Methods: In one eye, an acute IOP elevation was induced in minipigs and compared to the other control eye. Activity and amount of respiratory chain complexes (RCC) were analyzed by spectrophotometry and Western blot, respectively. The coenzyme Q10 (CoQ10) content was measured using HPLC, and the ultrastructure of the mt was studied via transmission electron microscopy. The expression of selected mt-pathway genes was determined by RT-PCR. Results: At a functional level, increased RCC I activity and decreased total CoQ10 content were found in RPE cells. At a protein level, CORE2, a subunit of RCC III, and DRP1, was significantly decreased in the neuroretina. Drp1 and Opa1, protein-encoding genes responsible for mt quality control, were decreased in most of the samples from the RPE and neuroretina. Conclusions: The eyes of the minipig can be considered a potential RI model to study mt dysfunction in this disease. Strategies targeting mt protection may provide a promising way to delay the acute damage and onset of RI.

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

To study the associations between optic nerve head (ONH) strains under intraocular pressure (IOP) elevation with retinal sensitivity in patients with glaucoma. Clinic-based cross-sectional study. Two hundred twenty-nine patients with primary open-angle glaucoma (subdivided into 115 patients with high-tension glaucoma [HTG] and 114 patients with normal-tension glaucoma [NTG]). For 1 eye of each patient, we imaged the ONH using spectral-domain OCT under the following conditions: (1) primary gaze and (2) primary gaze with acute IOP elevation (to approximately 35 mmHg) achieved through ophthalmodynamometry. A 3-dimensional strain-mapping algorithm was applied to quantify IOP-induced ONH tissue strain (i.e., deformation) in each ONH. Strains in the prelaminar tissue (PLT), 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). This was performed globally, then locally according to a previously published regionalization scheme. Associations between ONH strains and values of retinal sensitivity from visual field testing. For patients with HTG, we found (1) 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 decibels [dB]), (2) that high-strain regions colocalized with anatomically mapped regions of high visual field loss, and (3) that the strongest negative associations were observed in the superior region and in the PLT. In contrast, for patients with NTG, no significant associations between strains and retinal sensitivity were observed except in the superotemporal region of the LC. We found significant negative associations between IOP-induced ONH strains and retinal sensitivity in a relatively large glaucoma cohort. Specifically, patients with HTG who experienced higher ONH strains were more likely to exhibit lower retinal sensitivities. Interestingly, this trend in general was less pronounced in patients with NTG, which could suggest a distinct pathophysiologic relationship between the two glaucoma subtypes.

Optical Coherence Tomography Angiography Findings after Acute Intraocular Pressure Elevation in Patients with Diabetes Mellitus versus Healthy Subjects.

Purpose To assess the changes in optic nerve head and macular microvascular networks after acute intraocular pressure (IOP) rise in healthy eyes versus the eyes of diabetic patients.MethodsIn this prospective, interventional, comparative study, 24 eyes of 24 adults including 12 eyes of healthy nondiabetic subjects and 12 eyes with mild or moderate non-proliferative diabetic retinopathy (NPDR) were enrolled. IOP elevation was induced by a suction cup attached to the conjunctiva. IOP and optical coherence tomography angiographic (OCTA) images of the optic disc and macula were obtained before and immediately after the IOP rise.ResultsBaseline and post-suction IOPs were not significantly different between the two groups (all P 0.05). The mean IOP elevation was 13.93 3.41 mmHg among all eyes and was statistically significant as compared to the baseline in both groups (both P 0.05). After IOP elevation, healthy eyes demonstrated a reduction in the vessel density in the whole image deep and superficial capillary plexuses and parafoveal deep capillary plexus (DCP) (all P 0.05). In diabetic retinopathy, foveal vessel density at DCP decreased significantly following IOP rise (P = 0.003). In both groups, inside disc vessel density decreased significantly after IOP rise (both P 0.05), however, no significant change was observed in peripapillary vessel density (both P 0.05).ConclusionAcute rise of IOP may induce different levels of microvascular changes in healthy and diabetic eyes. Optic disc microvasculature originating from the posterior ciliary artery may be more susceptible to IOP elevation than that of retinal microvasculature.

Acute intraocular pressure elevation after Nd:YAG laser-puncture of a post-traumatic iris cyst

A 55-year-old man with a previous history of penetrating corneal trauma presented with decreased vision in his right eye, especially in photopic conditions. The visual acuity was 20/40 in the right eye and 20/20 in the left eye. A rounded lesion with smooth, thin walls and low reflective content was observed in the anterior chamber (A and B), in contact with corneal endothelium, suggestive of an iris cyst from epithelial downgrowth.

Evaluation of neuroprotective agents acting via the BDNF–TrkB pathway using AI‐enabled predictions of ligand–receptor interactions

Glaucoma is the leading cause of irreversible blindness globally and is associated with retinal ganglion cell (RGC) death. Brain-derived neurotrophic factor (BDNF) is a potent neurotrophin that promotes neuronal survival via its receptor, tropomyosin receptor kinase B (TrkB) encoded by NTRK2. Our current understanding of the mechanism of action and therapeutic potential of the BDNF pathway is limited by the lack of knowledge of its interaction with TrkB at atomic resolution. We developed an artificial intelligence (AI) model to predict the three-dimensional protein structures of BDNF and TrkB, as well as their interaction. The AI model was further applied to compare small-molecule drugs that mimic BDNF–TrkB interaction, leading to the identification of 7,8-dihydroxyflavone (DHF) as an agonist of TrkB. We verified the neuroprotective effects of DHF in an in vivo acute glaucoma model in which RGC apoptosis caused by acute elevation of intraocular pressure was prevented by the intraocular application of DHF and to a lesser extent by BDNF. Our results provide AI-enabled prediction of ligand–receptor interactions between BDNF and TrkB at the atomic level and demonstrate the great potential for AI-enabled drug discovery.

Mechanical Deformation of Peripapillary Retina in Response to Acute Intraocular Pressure Elevation.

Elevated intraocular pressure (IOP) may cause mechanical injuries to the optic nerve head (ONH) and the peripapillary tissues in glaucoma. Previous studies have reported the mechanical deformation of the ONH and the peripapillary sclera (PPS) at elevated IOP. The deformation of the peripapillary retina (PPR) has not been well-characterized. Here we applied high-frequency ultrasound elastography to map and quantify PPR deformation, and compared PPR, PPS and ONH deformation in the same eye. Whole globe inflation was performed in ten human donor eyes. High-frequency ultrasound scans of the posterior eye were acquired while IOP was raised from 5 to 30 mmHg. A correlation-based ultrasound speckle tracking algorithm was used to compute pressure-induced displacements within the scanned tissue cross sections. Radial, tangential, and shear strains were calculated for the PPR, PPS, and ONH regions. In PPR, shear was significantly larger in magnitude than radial and tangential strains. Strain maps showed localized high shear and high tangential strains in PPR. In comparison to PPS and ONH, PPR had greater shear and a similar level of tangential strain. Surprisingly, PPR radial compression was minimal and significantly smaller than that in PPS. These results provide new insights into PPR deformation in response of IOP elevation, suggesting that shear rather than compression was likely the primary mode of IOP-induced mechanical insult in PPR. High shear, especially localized high shear, may contribute to the mechanical damage of this tissue in glaucoma.