Elevated IOP Research Articles

SPECIFICATIONS OF DIFFERENT IOP METHODS SPECIFICATIONS

IOP is an important risk factor for glaucoma, and lowering IOP, even when IOP is within the normal range as defined epidemiologically, remains the only proven-effective treatment of the disease.However, our knowledge of the true nature of IOP in humans or how it affects ocular tissues is partially limited by the lack of continuous IOP monitoring technology for patients.Although clinical IOP reduction remains the only proven method for preventing the occurrence and progression of glaucoma, the role of IOP in the development and progression of the disease is not well understood.This is largely due to clinical observation that a significant number of patients with normal IOP develop glaucoma, while other individuals with elevated IOP show no signs of disease.This may mean that IOP (or some IOP-driven factor) is the primary triggering factor in glaucoma, and IOP vulnerability varies among individuals.Another possibility is that the clinical characterization of the secondary IOP using rare imaging measurements fails to capture the exposure to harmful IOP fluctuations that partially drive the disease in these normotensive patients with glaucoma, which contributes to the IOP-gloomy relationship.Recent data suggest that the IOP varies around 5 mmHg daily and hourly, and from 15 to 40 mmHg per second when measured continuously in awake patients.Very little is known about IOP fluctuations in humans and how The eye responds to these fluctuations, but IOP levels at all time points have the potential to cause disturbances in the neuroretic layer.Intraocular pressure assessment (IOP) is a key phase of routine eye examination, especially for patients with glaucoma. Indeed, in these cases, elevated IOP is the only risk factor that physicians can modify.This is why the IOP value is important to the patient: it is a key element in the diagnosis and management of glaucoma.The IOP depends on the speed of movement and the rate of leakage of the guiding light, ie it depends on the flow resistance ofн the drainage channels and the amount of episcleral venous pressure.Glaucoma is a slowly progressive neuropathy with changes in the optic nerve, retinalneurofibrillary layer (RNFL) and visual field.

Rapid Development of Glaucoma Via ITV Nonselective ANGPT 1/2 Antibody: A Potential Role for ANGPT/TIE2 Signaling in Primate Aqueous Humor Outflow.

Investigate a significant, dose-related increase in IOP, leading to glaucomatous damage to the neuroretina and optic nerve following intravitreal (ITV) administration of a bispecific F(ab')2 [anti-VEGF/Angiopoietins [ANGPT]F(ab')2] molecule in adult monkeys. ITV ocular tolerability and investigation of anti-VEGF/ANGPT F(ab')2 (blocking both ANGPT1 and ANGPT2) was done in monkeys; mechanistic studies were done in neonatal mice. Following the second ITV dose of anti-VEGF/ANGPT F(ab')2, all 1.5- and 4-mg/eye treated monkeys developed elevated IOP, which eventually was associated with optic disc cupping and thinning of the neuroretinal rim. Histopathologic examination showed nonreversible axonal degeneration in the optic nerves of animals administered 1.5 mg/eye and higher that was considered secondary to high IOP. Anti-ANGPT Fab also caused elevated IOP in monkeys, but anti-VEGF Fab did not contribute to the IOP increase. In addition, an anti-ANGPT2-selective antibody did not change IOP. In mice simultaneous blockade of ANGPT1 and ANGPT2 impaired the expansion and formation of Schlemm's canal (SC) vessels, similar to genetic ablation of Angpt1/Angpt2 and their receptor TIE2. As previously reported, blocking ANGPT2 alone did not affect SC formation in mice. Dual inhibition of ANGPT1/ANGPT2, but not ANGPT2 alone, leads to increased IOP and glaucomatous damage in monkeys. This confirms a role for TIE2/ANGPT signaling in the control of IOP in adults, a finding initially identified in transgenic mice. Dual pharmacologic inhibition of ANGPT1/ANGPT2 may affect aqueous drainage and homeostasis in adult monkeys and may be useful in developing novel models of glaucoma.

Intraocular pressure (IOP) after intravitreal dexamethasone implant (Ozurdex) amongst different geographic populations-GEODEX-IOP study.

To analyse the intraocular pressure rise after intravitreal dexamethasone implant (Ozurdex) amongst different geographic populations. The medical charts of 294 dexamethasone implants between February 2011 and 2017 were reviewed retrospectively. South Asian (India), White (Europe, US and Israel) Latino (Argentina and Brazil) patient data was included in the study. Ocular hypertension (OHT) was defined as intraocular pressure of >25 mmHg or an increase of at least 10 mmHg from baseline. The main indications for treatment were diabetic macular edema (ME) (65.6%), retinal vein occlusion (26.5%), uveitis (7.8%). Amongst 294 intravitreal implants, ocular hypertension (>25 mmHg) was recorded in 0, 8 and 9.5% in White, Latino, and South Asian groups, respectively. However, IOP > 20 mmHg was recorded in 14%, 28% and 27% in White, Latino, and South Asian groups, respectively. Incidence of very high IOP (>35 mmHg) was lower in all geographical groups. It was 3% in Latino followed by 2% in South Asian group. Latino and South Asian groups have higher IOP rise compared to White population. Most patients with elevated IOP fluctuate between 20-25 mmHg.

Nucleus Drop or Intraocular Lens Drop Underwent Pars Plana Vitrectomy due to Complication of Cataract Surgery

Abstract
 Background: The incidence of nucleus drop or intraocular lens (IOL) drop as the complication of phacoemulsification increases due to the increased frequency of phacoemulsification. Pars plana vitrectomy (PPV) followed by endofragmentation and secondary IOL implantation is the choice of procedure for management. This study aims to determine the frequency, outcomes, and complication of PPV in the case of nucleus drop or IOL drop in the Department of Ophthalmology, Fakultas Kedokteran Universitas Indonesia – Rumah Sakit Cipto Mangunkusumo (FKUI-RSCM)
 Methods: This study is a retrospective descriptive study conducted in the Vitreoretinal Division of the Department of Ophthalmology, FKUI - RSCM. Research data was taken from the medical records of all nucleus drop or IOL drop patients underwent PPV in January 2017-December 2017.
 Results: There were 19 cases studied. The incidence of nucleus drop occurred in phacoemulsification surgery techniques (94.7%) and ECCE techniques (5.3%). Vitrectomy surgery was performed ≤2 weeks in 31.6% and >2 weeks in 68.4% after the patient first arrived at the vitreoretinal clinic. Most pre-PPV visual acuity was 1/60-6/60 (47.1%). In the final follow-up, visual acuity improved from 6/45 to 6/6 occurred in 42.2% of cases. Complication after PPV and secondary IOL implantation include elevated IOP (10.5%), IOL decentration (5.3%), corneal decompensation (5.3%), macular edema (5.3%), and retinal detachment (5.3%).
 Conclusion: Nucleus drop or IOL drop generally occurs in phacoemulsification cataract surgery techniques. Improved visual acuity was achieved after PPV and secondary IOL implantation at the end of the follow-up period. Most common post-PPV complication is elevated IOP.

To evaluate the effect of intravitreal bevacizumab on intraocular pressure

Introduction: To assess intraocular pressure variation after intravitreal bevacizumab injection in patients with diabetic macular edema. Materials and Methods: Our prospective study included 20 eyes of patients who received intravitreal injection of 0.05 ml bevacizumab as treatment option for diabetic macular edema. IOP was recorded before the injection, at 3 days, 1week, 1month and 2 months after the intravitreal injection. Results: The mean intraocular pressure before injection was 17.28±3.04 mmHg. The mean IOP post bevacizumab at 3 days, 1 week, 1month and 2 months were 19.98± 3.23mmHg, 18.99±3.67 mmHg, 17.31±3.19 and 17.15±3.10 respectively. There was statistically significant elevation in IOP at 3 days post bevacizumab injection, which reinstated to baseline levels at final follow-up. Conclusion: Our study indicate that intravitreal injection of bevacizumab is associated with short term IOP elevation. Keywords: Bevacizumab, Clinically significant macular edema, Diabetic macular edema, GAT, IOP.

Reversibility of Retinal Ganglion Cell Dysfunction From Chronic IOP Elevation.

To test the hypothesis that the capacity for retinal ganglion cells to functionally recover from chronic IOP elevation is dependent on the duration of IOP elevation. IOP elevation was induced in one eye in anesthetized (isoflurane) adult C57BL6/J mice using a circumlimbal suture. Sutures were left in place for 8 and 16 weeks (n = 30 and 28). In two other groups the suture was cut after 8 and 12 weeks (n = 30 and 28), and ganglion cell function (electroretinography) and retinal structure (optical coherence tomography) were assessed 4 weeks later. Ganglion cell density was quantified by counting RBPMS (RNA-binding protein with multiple splicing)-stained cells. With IOP elevation (∼10 mm Hg above baseline), ganglion cell function declined to 75% ± 8% at 8 weeks and 59% ± 4% at 16 weeks relative to contralateral control eyes. The retinal nerve fiber layer was thinner at 8 (84% ± 4%) and 16 weeks (83% ± 3%), without a significant difference in total retinal thickness. Ganglion cell function recovered with IOP normalization (suture removal) at week 8 (97% ± 7%), but not at week 12 (73% ± 6%). Ganglion cell loss was found in all groups (-8% to -13%). In the mouse circumlimbal suture model, 12 weeks of IOP elevation resulted in irreversible ganglion cell dysfunction, whereas retinal dysfunction was fully reversible after 8 weeks of IOP elevation.

Cellular and cytoskeletal alterations of scleral fibroblasts in response to glucocorticoid steroids

Steroid-induced ocular hypertension can be seen even after trabecular meshwork (TM) bypass/ablation. Thus, the purpose was to investigate steroid-response in cells distal to the TM by using primary scleral fibroblasts. Primary scleral cell cultures were generated using mid-depth scleral wedges from human donor corneo-scleral rims (n = 5) after corneal transplantation. Cells were treated with dexamethasone (DEX; 100 nM) and compared to media (MED)/vehicle (DMSO) controls. Cell size, shape, and migration were studied using the IncuCyte Live-Cell Analysis System. Cytoskeleton was compared using Alexa Fluor-568 Phalloidin and senescence tested by evaluating beta-galactosidase. Western blot comparison was performed for α-SMA, FKBP-51, fibronectin, phospho-myosin light chain, and myocilin. Scleral fibroblasts upregulated FKBP-51 in response to DEX indicating the existence of steroid-responsive pathways. Compared to controls, DEX-treated cells proliferated slower (~50%; p < 0.01–0.02), grew larger (~1.3-fold; p < 0.001), and migrated less (p = 0.01–0.006). Alexa Fluor 568 Phalloidin actin stress fiber labeling was more diffuse in DEX-treated cells (p = 0.001–0.004). DEX-treated cells showed more senescence compared to controls (~1.7-fold; p = 0.01–0.02). However, DEX-treated cells did not show increased cross-linked actin network formation or elevated myocilin/fibronectin/α-SMA/phospho-myosin light chain protein expression. For all parameters, MED- and DMSO-treated control cells were not significantly different. Primary scleral fibroblasts, grown from tissue collected immediately distal to the TM, demonstrated scleral-response behaviors that were similar to, but not identical with, classic TM steroid-response. Further study is needed to understand how these scleral cellular alterations may contribute to steroid-response IOP elevation after TM bypass/ablation surgery.

Mitochondrial-Targeted Antioxidants Attenuate TGF-β2 Signaling in Human Trabecular Meshwork Cells.

POAG is a progressive optic neuropathy that is currently the leading cause of irreversible blindness worldwide. While the underlying cause of POAG remains unclear, TGF-β2-dependent remodeling of the extracellular matrix (ECM) within the trabecular meshwork (TM) microenvironment is considered an early pathologic consequence associated with impaired aqueous humor (AH) outflow and elevated IOP. Early studies have also demonstrated markedly elevated levels of oxidative stress markers in AH from POAG patients along with altered expression of antioxidant defenses. Here, using cultured primary or transformed human TM cells, we investigated the role oxidative stress plays at regulating TGF-β2-mediated remodeling of the ECM. Primary or transformed (GTM3) human TM cells conditioned in serum-free media were incubated in the absence or presence of TGF-β2 and relative changes in intracellular reactive oxygen species (ROS) were measured using oxidation-sensitive fluorogenic dyes CellROX green or 6-carboxy-2',7'-dichlorodihydrofluorescein diacetate (carboxy-H2DCFDA). TGF-β2-mediated changes in the content of connective tissue growth factor (CTGF) and collagen types 1α1 (COL1A1) and 4α1 (COL4A1) mRNA or collagens I and IV isoform proteins were determined in the absence or presence of mitochondrial-targeted antioxidants (XJB-5-131 or MitoQ) and quantified by quantitative PCR or by immunoblot and immunocytochemistry. Smad-dependent canonic signaling was determined by immunoblot, whereas Smad-dependent transcriptional activity was quantified using a Smad2/3-responsive SBE-luciferase reporter assay. Primary or transformed human TM cells cultured in the presence of TGF-β2 (5 ng/mL; 2 hours) exhibited marked increases in CellROX or fluorescein fluorescence. Consistent with previous reports, challenging cultured human TM cells with TGF-β2 elicited measurable increases in regulated Smad2/3 signaling as well as increases in CTGF, COL1A1, and COL4A1 mRNA and collagen protein content. Pretreating human TM cells with mitochondrial-targeted antioxidants XJB-5-131 (10 μM) or MitoQ (10 nM) attenuated TGF-β2-mediated changes in Smad-dependent transcriptional activity. The multifunctional profibrotic cytokine TGF-β2 elicits a marked increase in oxidative stress in human TM cells. Mitochondrial-targeted antioxidants attenuate TGF-β2-mediated changes in Smad-dependent transcriptional activity, including marked reductions in CTGF and collagen isoform gene and protein expression. These findings suggest that mitochondrial-targeted antioxidants, when delivered directly to the TM, exhibit potential as a novel strategy by which to slow the progression of TGF-β2-mediated remodeling of the ECM within the TM.

Indicators of Post-Operative Intraocular Pressure Elevation after Naïve Fluocinolone Acetonide Surgical Implantation

ABSTRACT Purpose To determine factors conferring an increased risk of developing ocular hypertension secondary to the fluocinolone acetonide (FA) sustained-release surgical implant (Retisert). Design Retrospective, observational case series. Methods Patients with a history of chronic noninfectious posterior uveitis undergoing naïve surgical FA implantation from 2007 to 2018 at the University of Colorado were studied. Patient demographics and multiple clinical measures were noted one year before and after FA implantation. Results Twenty-nine eyes of 21 patients were studied. The median age experiencing an IOP rise vs median age experiencing no IOP rise post-FA implantation was 27.0 and 54.0 years old, respectively (p = .01). A pre-FA implant risk factor of needing future glaucoma surgery after FA implantation is prior to maximum IOP (p = .02). Conclusions A risk factor of elevated post-FA implantation IOP includes younger age. A potential risk factor for glaucoma surgery after FA implantation was higher maximum IOP before FA implantation.

Outcomes of Using Sutureless, Scleral-Fixated Posterior Chamber Intraocular Lenses

ABSTRACTBackground. Implantation of sutureless, scleral-fixated posterior chamber intraocular lenses (SSFIOL) is a promising option in the surgical management of patients unable to undergo standard cataract surgery due to insufficient capsular support. The purpose of this study was to describe the indications, visual outcomes and complications of SSFIOL implantation.Methods. Retrospective, investigational cohort study of 112 consecutive SSFIOL implantations between July 2013 and August 2017. Pre-operative ocular morbidity, operative indications, postoperative outcomes, complications, and reinterventions were summarized. Visual and refractive outcomes were compared between the pre- and latest postoperative visit using Wilcoxon signed-ranked test.Results. Mean follow-up: 13.0 ± 10.4 months. Primary surgical indication was dislocated IOL due to zonular weakness (77 eyes (68.8%)). At latest follow-up, there was improvement in uncorrected visual acuity (1.3 ± 0.8 to 0.64 ± 0.60 logMAR, p < .01), best-corrected visual acuity (BCVA) (0.6 ± 0.5 logMAR to 0.36 ± 0.40 logMAR, p < .01). Postoperative complications included transient IOP elevation >30 mmHg (26.8%), cystoid macular edema (CME) (14.3%), transient hypotony (13.4%), iris capture (12.5%), uveitis-glaucoma-hyphema (UGH) syndrome (11.6%), vitreous hemorrhage (VH) (6.3%). Operative reinterventions included SSFIOL exchange (3.6%), SSFIOL repositioning (5.4%), SSFIOL removal (2.7%). Ten (8.9%) patients required multiple re-interventions.Conclusion. SSFIOL implantation is a reasonable option for eyes with inadequate capsular support, resulting in visual improvement in most patients. Many of the surgical complications were related to a floppy iris-lens diaphragm (UGH syndrome, iris capture), which were predisposed in eyes with complex pathology. Surgical modifications can be made to minimize the iris-related complications.

Incidence and outcomes of ocular hypertension from rhegmatogenous retinal detachment surgery in the acute postoperative setting.

PurposeTo determine the incidence of ocular hypertension following surgery for rhegmatogenous retinal detachment in the first 3 months postoperatively and to determine their outcomes in terms of visual acuity, control of IOP, and changes in cup:disc ratio.Patients and methodsA single center prospective cohort study was done involving patients who underwent retinal surgery for rhegmatogenous retinal detachment. The patients were followed up for 3 months postoperatively and were monitored for development of ocular hypertension. The primary outcome measures were changes in IOP, visual acuity, and cup:disc ratio.ResultsOf the 52 eyes enrolled in the study, 19 eyes developed ocular hypertension in the first 3 months postoperatively, giving an incidence rate of 36.5% (95% CI, 48.9–76.0%). Analysis of mean IOP trends shows that most cases of IOP elevations occur in the first day postoperatively with a sustained elevation up to the first month and then returning to normal levels by the 3rd month. There is a significant increase in mean cup:disc ratio among patients who developed ocular hypertension (p=0.047). Visual acuity trends show that mean visual acuity significantly improved from baseline among cases who maintained normal IOP (p=0.002) as compared to those who developed ocular hypertension (p=0.97), although the difference in final visual acuity at the end of 3 months between groups was not statistically significant (p=0.30).ConclusionOcular hypertension may complicate retinal reattachment surgery. Control of IOP in the acute setting is essential to prevent development of secondary glaucoma.

Ab interno tube ligation for refractory hypotony following non-valved glaucoma drainage device implantation

PurposeTo report the 2-year outcomes of a novel surgical technique allowing reduction of the intraluminal diameter of the tube without total tube occlusion in order to allow enough increase in outflow resistance to permit resolution of hypotony whilst also achieving adequate IOP control.MethodsThis was a single-surgeon retrospective case note review of all non-valved GDD cases over an 8-year period (2008–2015) that underwent ab interno ligation of the drainage tube in order to manage post-operative hypotony (Baerveldt or Molteno). Twelve eyes of 12 patients (4.4%) developing refractory hypotony that did not respond to multiple intracameral ophthalmic viscoelastic device (OVD) injections were included in this retrospective case series and were treated with our ab interno tube ligation technique. The post-ligation management algorithm consisted of re-instating topical anti-glaucoma agents, laser suture lysis (LSL), or further ab interno ligation.ResultsMean IOP increased from 2.8 mmHg at baseline to 7.8 mmHg, 7.1 mmHg, 9.0 mmHg, 13.6 mmHg, 10.9 mmHg, 13.9 mmHg and 13.6 mmHg at day 1, week 1, month 1, month 3, month 6, year 1 and year 2 respectively, with or without additional topical anti-glaucoma medications. Although hypotony resolution following our technique was achieved in all eyes at 2 years, 8.3% of cases required reinstatement of topical medications to maintain IOP control within the target range.ConclusionsWe propose ab interno partial tube tying as an effective surgical option to achieve an immediate, predictable and sustained IOP elevation either as a primary procedure or when traditional methods have failed to resolve hypotony in eyes with non-valved GDDs.

Effect of YAG Laser Posterior Capsulotomy on Central Macular Thickness in Pseudophakic Patients

Background: posterior capsular opacification (PCO), also known as ‘secondary cataract’ or ‘after cataract’, develops a few months to a few years over the clear posterior capsule after an uncomplicated cataract surgery. Purpose: evaluation the impact of Neodymium-doped Yttrium Aluminum-Garnet (Nd: YAG) laser capsulotomy on central macular thickness (CMT) by optical coherence tomography (OCT). Patients and Methods: the present study examined 50 eyes (24 males, 26 females) with an average age of 63.58±7.7 which was pseudophakic and had PCO, preoperative evaluation included history taking, ophthalmological examination and OCT was done. All patients underwent YAG laser posterior capsulotomy and CMT assessed at 3 days, 1 week, 1 month and 3 months by OCT. Results: there was significant improvement of BCVA (LogMAR) post laser capsulotomy (P< 0.001), IOP statistically significant increased (P< 0.001) at the first postoperative 3 days, 1 week, 1 month with mean ±SD of 16.46±2.54 mmHg 17.50±2.67 mmHg ,15.50±2.39 mmHg respectively when compared to preoperative values 13.0±1.67 mmHg. At 3 months there was minimal change (P=0.02). As regard CMT values at 1 week post laser (mean ±SD of 270.92±24.88) was highly significant increased (P< 0.001) and values at 3 months (mean ±SD of 248.70±21.66) showed nonsignificant difference (P=0.285) when compared to pre laser values (mean ±SD of 245.58±23.30). Conclusion: typical treatment of the PCO is YAG laser capsulotomy, IOP elevation is the most prevalent complication so antiglaucoma drugs is recommended and IOP return to normal values in the follow up period.

The role of self-dependent tonometry in improving diagnostics and treatment of patients with open angle glaucoma

Monitoring intraocular pressure in patients with open-angle glaucoma at different stages of the development of the disease using self-measurement by a portable Icare HOME tonometer. In study, patients were divided into 3 groups depending on the treatment prescribed. With the help of near-day monitoring, hidden IOP elevations that are not recorded during a single IOP measurement on an outpatient appointment with a doctor were detected. Perspective possibilities of prescribing drugs and regulating the mode of instillation on the basis of individual time periods of increasing intraocular pressure on the example of one of the patient. Assessment of the convenience of the method from the personal experience of using the device by patients.

&lt;p&gt;Comparison of successful outcome predictors for MicroPulse&lt;sup&gt;®&lt;/sup&gt; laser trabeculoplasty and selective laser trabeculoplasty at 6 months&lt;/p&gt;

Purpose: To identify and compare factors predictive of successful outcome for MicroPulse® laser trabeculoplasty (MLT) and selective laser trabeculoplasty (SLT).Methods: 50 MLT-treated eyes and 50 SLT-treated eyes of open-angle glaucoma patients were reviewed for baseline characteristics, pre- and postoperative IOP and medications, and adverse events including postoperative IOP elevation >5 mmHg (IOP spikes) through 6 months of follow-up. Success was defined as ≥20% IOP reduction or ≥1 medication reduction without additional IOP lowering procedures at 6 months follow-up.Results: MLT and SLT had similar success rates (44% vs 40%, P=0.983). Older age predicted success for SLT (P=0.013) but not MLT (P=0.154). Both MLT and SLT led to greater IOP lowering in patients with baseline IOP >18 mmHg, but only for SLT did baseline IOP have a significant association with success (P=0.035 vs P=0.983). Number of laser shots was associated with success in MLT (P=0.031) but not in SLT (P=0.970). Glaucoma severity and pigmentation of the trabecular meshwork (PTM) were not associated with rate of success for either group. The rate of IOP spikes was significantly (P=0.022) higher in the SLT group (10%) compared to none in the MLT group. No other complications or visually significant adverse events occurred in either group.Conclusion: Although MLT and SLT resulted in similar success rates, older age and higher baseline IOP predicted success for SLT while MLT was equally efficacious regardless of these factors. Glaucoma severity and PTM were not associated with success of either laser procedures. 10% of SLT patients experienced IOP spike post procedure, whereas none in the MLT group did. MLT may be a safer alternative to SLT that is effective in lowering IOP and need for medications for a wider variety of patients with open angle glaucoma.

Effects of Salidroside on Trabecular Meshwork Cell Extracellular Matrix Expression and Mouse Intraocular Pressure.

Excessive accumulation of extracellular matrix (ECM) in the trabecular meshwork (TM) reduces aqueous humor outflow, which likely contributes to elevation of IOP in primary open-angle glaucoma (POAG). Salidroside, a phenolic glycoside isolated from Rhodiola rosea is reported to prevent profibrotic responses by inhibiting Smad signaling pathway activated by TGF-β in liver, lung, and kidney tissues. We tested if salidroside can (1) inhibit TGF-β2-induced ECM expression in cultured human TM cells, and (2) lower TGF-β2-induced ocular hypertension in the mouse. Cultured human TM cells stimulated with 5 ng/mL TGF-β2 for 48 hours were treated with salidroside for 24 hours. The expressions of fibronectin (FN), collagen type IV (COL-IV), and laminin (LN) were evaluated by quantitative PCR, Western blot, and immunocytochemistry. BALB/cJ mice were injected intravitreally with an adenoviral vector encoding a bioactive mutant of TGF-β2 (Ad.hTGF-β2226/228) in one eye to induce ocular hypertension, with the uninjected contralateral or Ad.Empty-injected eyes serving as controls. Mice were treated with a daily intraperitoneal injection of 40 mg/kg salidroside. Conscious mouse IOP values were measured using a TonoLab rebound tonometer. In cultured human TM cells, treatment with TGF-β2 increased expressions of FN, COL-IV, and LN, as assessed by quantitative PCR, Western blotting, and immunocytochemistry, all of which were significantly and completely ameliorated by 30 μM salidroside. Daily intraperitoneal injections of salidroside (40 mg/kg), starting either at day 0 (same day as Ad.hTGF-β2226/228 injection) or at day 14, significantly lowered TGF-β2-induced ocular hypertension in the mouse. In contrast, salidroside did not affect IOP of control eyes. These results demonstrated that salidroside is capable of minimizing TGF-β2-induced ECM expression in cultured human TM cells. It also reduced TGF-β2-induced ocular hypertension in the mouse. These findings indicate that this phenolic glycoside may be useful as a novel treatment for POAG.

Clinical observation of a novel technique: transscleral suture fixation of a foldable 3-looped haptics one-piece posterior chamber intraocular lens implantation through scleral pockets with intact conjunctiva

BackgroundTo present the follow-up outcomes of a modified technique of transscleral suture fixation of posterior chamber intraocular lens (PCIOL) in eyes with inadequate capsule support.MethodsA retrospective chart review of 21 patients underwent transscleral suture fixation of a foldable 3-looped haptics one-piece PCIOL implantation through scleral pockets was conducted. Preoperative data and follow-up data for at least 3 months were collected for all patients.ResultsThe mean operative duration was 36.62 ± 10.70 min. The mean pre- and post-operative LogMAR uncorrected distance visual acuity was (1.25 ± 0.50 vs. 0.41 ± 0.22, P < 0.01). The mean pre- and post-operative LogMAR best corrected visual acuity was (0.48 ± 0.25 vs. 0.33 ± 0.24, P < 0.01). The mean proportion of postoperative endothelial cell loss was 11.46 ± 4.78%. The mean postoperative anterior chamber depth was 3.05 ± 0.44 mm. The mean postoperative IOL tilt degree was 2.81 ± 1.41°, and the mean postoperative IOL decentration degree was 0.31 ± 0.13 mm. Four patients with transient corneal edema (19.0%) and three patients with transiently elevated IOP (14.3%) were observed after operation, and such complications were resolved within 1 week. No severe complications were observed.ConclusionsThe modified technique was a feasible method of PCIOL implantation.

Optic nerve head damage relation to intracranial pressure and corneal properties of eye in glaucoma risk assessment.

This work presents results from numerical simulations of optic nerve head's (ONH) biomechanical behavior during exposure to elevated intraocular (IOP) and/or intracranial pressure (ICP) for ocular hypertension conditions. At the same time, a range of geometric and material properties of the eye structure and their interrelation with elevated IOP and ICP values are investigated. These simulations are performed on a generic model of the eye, which allows parametrical modification of geometric and material properties. Our main interest is in measuring ONH's potential damage in ocular hypertension due to intracranial pressure. Simulation results indicate a significant role of ICP in post-laminar neural tissue failure and a possible role of central corneal thickness (CCT) and scleral modulus in clinical assessment and treatment of patients with ocular hypertension (OHT). Specifically, CCT was found to affect ONH at early stages of damage in ocular hypertension conditions, and high scleral modulus seems to result in reduced shear failure in lamina cribrosa in a similar OHT state. These findings suggest that CCT could be a risk factor for glaucoma in OHT patients at initial stage along with cornea stiffness. Graphical abstract Graphical abstract.

This Issue of ACTA

This Issue of ACTA

Estimating three-dimensional outflow and pressure gradients within the human eye.

In this paper we set the previously reported pressure-dependent, ordinary differential equation outflow model by Smith and Gardiner for the human eye, into a new three-dimensional (3D) porous media outflow model of the eye, and calibrate model parameters using data reported in the literature. Assuming normal outflow through anterior pathways, we test the ability of 3D flow model to predict the pressure elevation with a silicone oil tamponade. Then assuming outflow across the retinal pigment epithelium is normal, we test the ability of the 3D model to predict the pressure elevation in Schwartz-Matsuo syndrome. For the first time we find the flow model can successfully model both conditions, which helps to build confidence in the validity and accuracy of the 3D pressure-dependent outflow model proposed here. We employ this flow model to estimate the translaminar pressure gradient within the optic nerve head of a normal eye in both the upright and supine postures, and during the day and at night. Based on a ratio of estimated and measured pressure gradients, we define a factor of safety against acute interruption of axonal transport at the laminar cribrosa. Using a completely independent method, based on the behaviour of dynein molecular motors, we compute the factor of safety against stalling the dynein molecule motors, and so compromising retrograde axonal transport. We show these two independent methods for estimating factors of safety agree reasonably well and appear to be consistent. Taken together, the new 3D pressure-dependent outflow model proves itself to capable of providing a useful modeling platform for analyzing eye behaviour in a variety of physiological and clinically useful contexts, including IOP elevation in Schwartz-Matsuo syndrome and with silicone oil tamponade, and potentially for risk assessment for optic glaucomatous neuropathy.