Moderate Intraocular Pressure Research Articles

Sigma-1 receptor agonist, (+)-pentazocine, is neuroprotective in a Brown Norway rat microbead model of glaucoma

PurposeGlaucoma is a worldwide leading cause of irreversible blindness. Standard treatments lower intraocular pressure (IOP). Novel treatments to prevent optic nerve (ON) degeneration are needed. Here, we investigate the hypothesis that sigma-1 receptor (S1R) agonist (+)-pentazocine (PTZ) is neuroprotective in a Brown Norway (BN) rat, microbead model of glaucoma. MethodsBN rats (9–11 weeks, male and female) were treated by intraperitoneal injection, 3 times per week with (+)-PTZ (2 mg/kg) or vehicle (VEH) alone. Treatment started 1 week prior to intraocular injection of polystyrene microbeads to elevate IOP. IOP was measured 2–3 times per week. Five weeks post microbead injection, rats were euthanized. ONs were removed, then fixed and processed for 63x oil, light microscope imaging of toluidine blue stained ON cross sections. To facilitate comparison of ON morphology from VEH and (+)-PTZ treated rats with similar ocular hypertensive insults, rats were assigned to low (IOP ≤15.8 mmHg), moderate (15.8 < IOP <28.0 mmHg), and high (IOP ≥28.0 mmHg) groups based on average IOP in the microbead injected eye. Axon numbers, axon density, axonal and glial areas, axon loss, and axon size distributions of naïve, bead, and contralateral ONs were assessed using QuPath program for automated image analysis. Results(+)-PTZ treatment of BN rats protected ONs from damage caused by moderate IOP elevation. Treatment with (+)-PTZ significantly reduced axon loss and glial areas, and increased axon density and axonal areas compared to ONs from VEH treated rats with moderate IOP. (+)-PTZ-mediated neuroprotection was independent of IOP lowering effects. At average IOP ≥28.0 mmHg, (+)-PTZ treatment did not provide measurable neuroprotection. ONs from contralateral eyes exhibited subtle, complex changes in response to conditions in the bead eyes. ConclusionsS1R agonist (+)-PTZ shows promise as a neuroprotective treatment for glaucoma. Future studies to understand the complex molecular mechanisms by which (+)-PTZ provides this neuroprotection are needed.

Human Umbilical Cord-Mesenchymal Stem Cells Survive and Migrate within the Vitreous Cavity and Ameliorate Retinal Damage in a Novel Rat Model of Chronic Glaucoma.

Glaucoma is the leading cause of irreversible blindness worldwide, and pathologically elevated intraocular pressure (IOP) is the major risk factor. Neuroprotection is one of the potential therapies for glaucomatous retinal damage. Intravitreal mesenchymal stem cell (MSC) transplantation provides a viable therapeutic option, and human umbilical cord- (hUC-) MSCs are attractive candidates for cell-based neuroprotection. Here, we investigated the ability of transplanted hUC-MSCs to survive and migrate within the vitreous cavity and their neuroprotective effects on chronic glaucomatous retina. For this, we developed a chronic ocular hypertension (COH) rat model through the intracameral injection of allogeneic Tenon's fibroblasts. Green fluorescent protein-transduced hUC-MSCs were then injected into the vitreous cavity one week after COH induction. Results showed that a moderate IOP elevation lasted for two months. Transplanted hUC-MSCs migrated toward the area of damaged retina, but did not penetrate into the retina. The hUC-MSCs survived for at least eight weeks in the vitreous cavity. Moreover, the hUC-MSCs were efficient at decreasing the loss of retinal ganglion cells; retinal damage was attenuated through the inhibition of apoptosis. In this study, we have developed a novel COH rat model and demonstrated the prolonged neuroprotective potential of intravitreal hUC-MSCs in chronic glaucoma.

Comparative study between timolol maleate and timolol - brimonidine combination in treatment of open-angle glaucoma of moderate intraocular pressure in a tertiary care hospital

To study the efficacy of Timolol Maleate Vs Timolol-Brimonidine combination in lowering the intraocular pressure (IOP) in primary open angle glaucoma (POAG) at a tertiary care hospital. To study any adverse effects of both drug therapies in treatment of POAG. Computerized simple randomization was followed in allocating the patients for the two groups. In each group, n=20, is the total number of patients, and N=30, is the total number of eyes tested, since both eyes were involved in some patients. The concentration of the monotherapy was 0.5% w/v Timolol Maleate and concentration of the combination therapy was 0.2% w/v Brimonidine Tartrate and 0.5% w/v Timolol Maleate. Both drugs were administered twice daily and IOP was recorded every 3 days, for a period of 4 weeks. Monotherapy of Timolol is seen to lower the IOP at 25% in 3 days, whereas the Timolol-Brimonidine combination therapy lowers the IOP at twice the rate that is 50% in 3 days. After reaching a IOP of 12mmHg, which is the normal IOP, both the drugs are used for maintenance therapy. Adverse effects were reported with both groups. Timolol monotherapy is also priced lower, when compared to Timolol-Brimonidine combination therapy. Timolol monotherapy provides the same result as the Timolol-Brimonidine combination therapy and is also comparatively cheaper. Hence, Timolol monotherapy is better suited for the treatment of POAG.

Measurement of the Intraocular Pressure Elevation During Laser-Assisted In Situ Keratomileusis Flap Creation Using a Femtosecond Laser Platform.

PurposeThe purpose of this study was to measure the intraocular pressure (IOP) elevation during laser assisted in situ keratomileusis (LASIK) flap creation using the WaveLight FS200 femtosecond (FS) laser platform.MethodsWe conducted an ex vivo experimental study in an animal model. The WaveLight FS200 FS laser platform was used to perform the corneal LASIK flap in freshly enucleated porcine eyes. We measured the changes in IOP from the application of the suction ring (suctioning phase) through the creation of the lamellar corneal flap (cutting phase). The IOP was recorded using a manometric technique with direct cannulation to the anterior chamber.ResultsNine freshly enucleated porcine eyes were included in the study. The mean baseline IOP before the procedure was 20.33 ± 5.9 mm Hg. The mean IOP increase over baseline IOP was 32.33 ± 11.3 mm Hg at the suctioning phase, and 38.22 ± 11.3 mm Hg at the cutting phase. The total surgical time needed to complete the procedure was 29.5 ± 4.4 seconds.ConclusionsThe WaveLight FS200 FS laser platform produces a low to moderate increase in IOP during LASIK flap creation.Translational RelevanceThe WaveLight FS200 is a safe FS laser platform because it induces a low to moderate IOP increase during LASIK flap creation.

Micropulse trans-scleral laser therapy outcomes for uncontrolled glaucoma: a prospective 18-month study

ObjectiveTo evaluate the efficacy and safety of micropulse trans-scleral laser therapy (mTLT) in glaucomatous patients. DesignProspective, interventional study in a university hospital setting. ParticipantsFifty-two eyes of 52 adult patients with uncontrolled glaucoma despite maximal tolerated medical treatment, and/or poor candidates for filtering surgery. MethodsParticipants received a 360-degree mTLT diode laser treatment (2000mW, 31.33% duty cycle), with duration adjusted to iris pigmentation and glaucoma severity (160–320 seconds). They were followed for 18 months to assess intraocular pressure (IOP), number of medications, corrected distance visual acuity (CDVA), glaucoma progression based on Humphrey Sita 24-2 perimetry and Cirrus high-definition optical coherence tomography, and complications. The primary outcome measure was the absolute success at 18 months. Absolute success was defined as an IOP 6–21 mm Hg and at least 25% IOP reduction, with equal or less number of IOP medications. Qualified success allowed for an increased number of IOP medications. Failure was defined as an inability to meet the criteria for success or the need for incisional glaucoma surgery. ResultsTreatment absolute success was 61.5% at 12 months and 59.6% at 18 months. Mean IOP was reduced by 35.6% at 18 months (23.6 ± 6.5 mm Hg at baseline; 15.2 ± 4.1 mm Hg at 18 months, p < 0.001). mTLT did not significantly reduce the number of topical glaucoma medications (p = 0.075); however, 15 eyes (29%) had systemic oral glaucoma treatment at baseline and 10 eyes (20%) at 18 months. Eight patients (15%) experienced vision loss of ≥2 lines after the procedure. Three patients (6%) regained their preoperative CDVA by 1 month, and 3 patients (6%) by 3 months, while 2 patients (4%) sustained persistent visual loss. No ocular complications were noted in 84.6%. Incisional surgery was required in 25% of eyes owing to inadequately controlled glaucoma despite mTLT. ConclusionsmTLT is a good therapeutic option for moderate IOP reduction, while being safe and predictable. This improved safety profile makes mTLT a treatment to be considered earlier in the management of glaucoma.

Initial experience with phacoemulsification and goniotomy using the Kahook dual blade in advanced open-angle glaucoma: Six-month outcomes in Indian eyes.

Purpose:The aim of this study was to report our initial experience on the outcomes of phacoemulsification in combination with goniotomy using the Kahook Dual Blade (KDB) in eyes with advanced open-angle glaucoma (OAG).Methods:The outcomes of phaco-goniotomy with KDB in advanced OAG in Indian eyes were retrospectively analyzed. Based on the Hodapp-Anderson-Parrish criteria of visual field defects, severe glaucoma (mean deviation on standard automated perimetry worse than 12 dB) was considered as advance glaucoma. Preoperative, intraoperative, and postoperative data were collected through 6 months of follow-up. Outcome measures included antiglaucoma medications (AGM), the proportion of eyes achieving >1AGM reduction, intraocular pressure (IOP), and visual acuity.Results:Median (interquartile range) number of AGM in eyes that underwent phaco-KDB goniotomy reduced from 2 (2,3) at baseline to 1 (0,1) at 6 months (P = 0.002). Median IOP reduced from 20 (20,26) mmHg at baseline to 14 (12,15) mmHg at 6 months (P = 0.02). The proportion of eyes achieving >1 medication reduction was 88% eyes (8/9). Adverse events noted were IOP spike (22 mmHg) in 2 eyes and intra-op hyphema in 1 eye on postoperative day-1, both resolved in a week with conservative management. Except one eye with central corneal scar due to prior pterygium surgery, 8 eyes had 20/20 vision at 1 week which was maintained till last follow-up.Conclusion:Phacoemulsification with KDB Goniotomy significantly lowered the need for AGM with moderate IOP reduction in advanced OAG eyes. There were no serious complications and the visual recovery was good and early.

Elevated intraocular pressure causes cellular and molecular retinal injuries, advocating a more moderate intraocular pressure setting during phacoemulsification surgery.

To evaluate the cellular and molecular retinal injuries induced by various intraocular pressure (IOP) settings in a mouse model of acute ocular hypertension (AOH), and to advise using a more moderate target IOP during phacoemulsification (phaco) surgery. A mouse model of AOH that mimics a transient IOP elevation during phacoemulsification cataract surgery was established. Six groups with various settings of target IOP were included. Retinal tissues were assessed with terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end-labeling (TUNEL) staining for neuron loss, immunofluorescence with Iba1 for microglia activation, and quantitative real-time polymerase chain reaction analysis with tight junction proteins (claudin-3 and claudin-5) or classic inflammation markers (IL-1β and eNOS) for impairment of the blood-retinal barrier (BRB) and inflammatory injury. Compared with those in the 45-mmHg IOP group, significantly increased number of neurons loss and increased microglia activation were observed in 90-mmHg IOP group. In addition, the expression of claudin-3 and claudin-5 was significantly decreased, while the expression of IL1-β and eNOS was up-regulated, indicating impairment of the BRB and inflammatory injury in the retina. Furthermore, these findings of neuron loss, microglia activation, and inflammation in the 90-mmHg groups were exacerbated when an IOP-induced retinal injury was established 5days earlier, while those in the 45-mmHg groups remained almost unchanged. In conclusion, these results showed that a relatively commonly used high IOP setting (90mmHg) could induce significantly more serious retinal injury. An IOP setting around 45mmHg is relatively safe and might be recommended in phaco surgery, especially in patients with advanced glaucoma, previous acute angle closure crisis, or other diseases with fragile retina and optic nerve.

Longitudinal outcomes of circumlimbal suture model-induced chronic ocular hypertension in Sprague-Dawley albino rats.

To characterise longitudinal structural and functional changes in albino Sprague-Dawley rats following circumlimbal suture ocular hypertension (OHT) induction. Ten-week-old rats (n = 24) underwent suture implantation around the limbal region in both eyes. On the next day, the suture was removed from one eye (control eyes) and left intact in the other eye (OHT eyes) of each animal. Intraocular pressure (IOP) was monitored weekly twice for the next 15weeks. Optical coherence tomography (OCT) and electroretinogram (ERG) were measured at baseline and weeks 4, 8, 12, and 15, and eyes were then collected for histological assessment. Sutured eyes (n = 12) developed IOP elevation of ~ 50% in the first 2 weeks that was sustained at ~ 25% above the control eye up to week 15 (p = 0.001). Animals with insufficient IOP elevation (n = 6), corneal changes (n = 3), and attrition (n = 3) were excluded from the analysis. OHT eyes developed significant retinal nerve fibre layer (RNFL) thinning (week 4: - 19 ± 14%, p = 0.10; week 8: - 17 ± 12%, p = 0.04; week 12: - 16 ± 10%, p = 0.04, relative to baseline) and reduction in retinal ganglion cell (RGC) density (- 32 ± 26%, p = 0.02). At week 15, both inner (9 ± 7%, p = 0.01) and outer retinal layer thicknesses (6.0 ± 5%, p = 0.001) showed a mild increase in thicknesses. The positive scotopic threshold response (- 28 ± 25%, p = 0.04) and a-wave were significantly reduced at week 12 (- 35 ± 21%; p = 0.04), whereas b-wave was not significantly affected (week 12: - 18 ± 27%, p = 0.24). The circumlimbal suture model produced a chronic, moderate IOP elevation in an albino strain that led to RNFL thinning and reduced RGC density along with the reductions in ganglion and photoreceptoral cell functions. There was a small thickening in both outer and inner retinal layers.

Neuroretinal rim response to transient changes in intraocular pressure in healthy non-human primate eyes

Optic nerve head (ONH) neuroretinal rim thickness, quantified as minimum rim width (BMO-MRW), is a sensitive measure for assessing early glaucomatous disease. The BMO-MRW is sensitive to transient fluctuations in intraocular pressure (IOP), but the time course over which BMO-MRW decreases and recovers with changes in IOP remains unknown. The goal of this study was to investigate the dynamics of BMO-MRW changes over 2-h periods of mild or moderate IOP elevation, and subsequent recovery, in healthy non-human primate eyes. Eight non-human primates were included in the study. For each animal, in two different sessions separated by at least 2 weeks, the anterior chamber IOP of one eye was maintained at either 25 mmHg or 40 mmHg for 2 h and, subsequently, at 10 mmHg for 2 h. For the duration of anterior chamber cannulation, optical coherence tomography (OCT) radial scans centered on the ONH were acquired every 5 min and used to quantify BMO-MRW. An exponential decay or rise to maximum function was used to determine the extent and rate of structural change. Additionally, Bruch's membrane opening (BMO) area, BMO height/displacement, and BMO-referenced anterior lamina cribrosa surface depth (BMO-ALCSD) were computed from radial scans. A circular scan was used to quantify retinal nerve fiber layer thickness (RNFLT) and circumpapillary choroid thickness. The primary results demonstrated that the BMO-MRW changed over an extended duration, while BMO displacement was rapid and remained stable with sustained IOP. The mean maximum predicted BMO-MRW thinning following 2 h of IOP elevation was significantly related to pressure (34.2 ± 13.8 μm for an IOP of 25 mmHg vs 40.5 ± 12.6 μm for 40 mmHg, p = 0.03). The half-life for BMO-MRW thinning was 21.9 ± 9.2 min for 25 mmHg and 20.9 ± 4.2 min for 40 mmHg, not significantly different between IOP levels (p = 0.76). Subsequently, after 2 h of IOP at 10 mmHg, all animals exhibited partial recovery of BMO-MRW with similar degrees of persistent residual thinning for the two IOP levels (21.5 ± 13.7 vs 21.0 ± 12.3 μm, p = 0.88). Similar to BMO-MRW, choroid thickness exhibited gradual thinning with IOP elevation and residual thinning following IOP reduction. However, there was no significant change in BMO area or BMO-ALCSD in either experimental session. The RNFLT gradually decreased over the duration of IOP elevation, with continued decreases following IOP reduction for the 40 mmHg session, resulting in total changes from baseline of −2.24 ± 0.81 and −2.45 ± 1.21 μm for 25 and 40 mmHg, respectively (p < 0.001). The sum of the results demonstrate that the ONH neural tissue is sensitive to changes in IOP, the effects of which are gradual over an extended time course and different for increased vs. decreased pressure. Understanding the duration over which IOP influences BMO-MRW has important implications for studies investigating the effects of IOP on the ONH. Additionally, individual variability in ONH response to IOP may improve our understanding of the risk and progression of disease.

Comparability of three intraocular pressure measurement: iCare pro rebound, non-contact and Goldmann applanation tonometry in different IOP group

BackgroundMeasurement of intraocular pressure (IOP) is essential for glaucoma patients. Many factors such as central corneal thickness (CCT) can affect the accuracy of IOP measurement. The purpose of this study was to evaluate the agreement of IOP measured by non-contact tonometer (NCT), iCare pro rebound tonometer (iCare), and Goldmann applanation tonometer (GAT) in different IOP group.MethodsThis was a Hospital-based cross-sectional study. Two hundred subjects were enrolled in this study. All subjects underwent IOP measurement using an NCT–iCare–GAT sequence. Bland-Altman, Pearson correlation and intraclass correlation analysis were performed using SPSS 17.0 software. The influence of CCT on each IOP measurement methods was evaluated by linear regression analysis.ResultsThe mean difference (Δ) of NCT–GAT did not differ from (Δ) iCare–GAT in IOP < 10 and 10–21 mmHg group. However, (Δ) NCT–GAT was significantly higher than (Δ) iCare–GAT in IOP 22–30 and > 30 mmHg group (P < 0.05). Bland–Altman analysis showed significant agreement between the three devices (P < 0.01). IOP measurements of the three methods were significantly correlated with CCT (P < 0.01).ConclusionsICare pro shows a higher agreement with GAT over a wide range of IOP compared with NCT. The consistency between the three tonometers was similar in a low and normal IOP range. However, NCT shows a greater overestimate of IOP in moderate and higher IOP group. The variability of IOP measurement affected by CCT is NCT > iCare pro > GAT.

Changes in vessel density of the patients with narrow antenior chamber after an acute intraocular pressure elevation observed by OCT angiography

BackgroundAlthough the pathogenesis of glaucoma is not fully understood,an elevated intraocular pressure (IOP) is a major factor contributing to its development and progression. The aim of this study was to investigate the changes in the vessel densities of the macula and optic nerve head (ONH) after an acute elevation in the intraocular pressure (IOP) observed using optical coherence tomography angiography (OCTA).MethodsThis was a prospective comparative study of subjects with narrow anterior chamber angles who underwent laser peripheral iridotomies (LPIs). The IOP was measured before and one hour after the LPI. The retinal vessel densities of the macula and ONH were measured using OCTA at the baseline and one hour after the LPI.ResultsA total of 64 eyes of 51 individuals were enrolled in this study, and 58 eyes of 43 individuals finally completed the study with a mean IOP rise of 10.5 ± 7.6 mmHg after the LPI. Based on the magnitude of the rise in the IOP, we divided the subjects into three groups: group A = IOP rise ≤10 mmHg, group B = 10 mmHg < IOP rise ≤20 mmHg, and group C = IOP rise > 20 mmHg. The vessel density did not differ after the acute IOP elevation in either the macular region or papillary region in group A or group B (p > 0.05), but there was a significant difference in group C (p < 0.05). However, when the subjects were not separated into groups, the vessel densities of the ONH and macular region did not differ between the measurements obtained at the baseline and one hour after the LPI (p > 0.05). The correlation existed in peripapillary and macular vessel density (p < 0.05).ConclusionIn these subjects with narrow antenior chamber, an acute mild or moderate IOP elevation for one hour after the LPI did not affect the vessel density in the macula or ONH, as examined using OCTA. However, when the IOP rise was greater than 20 mmHg, the macular and papillary vessel density decreased significantly.

Intracameral injection of a chemically cross-linked hydrogel to study chronic neurodegeneration in glaucoma

Investigation of neurodegeneration in glaucoma, a leading cause of irreversible blindness worldwide, has been obfuscated by the lack of an efficient model that provides chronic, mild to moderate elevation of intraocular pressure (IOP) with preservation of optical media clarity for long term, in vivo interrogation of the structural and functional integrity of the retinal ganglion cells (RGCs). Here, we designed and formulated an injectable hydrogel based on in situ cross-linking of hyaluronic acid functionalized with vinyl sulfone (HA-VS) and thiol groups (HA-SH). Intracameral injection of HA-VS and HA-SH in C57BL/6J mice exhibited mild to moderate elevation of IOP with daily mean IOP ranged between 14 ± 3 and 24 ± 3 mmHg, which led to progressive, regional loss of RGCs evaluated with in vivo, time-lapse confocal scanning laser ophthalmoscopy; a reduction in fractional anisotropy in the optic nerve and the optic tract projected from the eye with increased IOP in diffusion tensor magnetic resonance imaging; a decrease in positive scotopic threshold response in electroretinography; and a decline in visual acuity measured with an optokinetic virtual reality system. The proportion of RGC loss was positively associated with the age of the animals, and the levels and the duration of IOP elevation. The new glaucoma model recapitulates key characteristics of human glaucoma which is pertinent to the development and pre-clinical testing of neuroprotective and neuroregenerative therapies. Statement of SignificanceA new model to study chronic neurodegeneration in glaucoma has been developed via intracameral injection of a specifically designed hyaluronic acid functionalized with vinyl sulfone and thiol groups for cross-linking. Intracameral injection of the chemically cross-linked hydrogel generates mild to moderate IOP elevation, resulting in progressive degeneration of the retinal ganglion cells, optic nerve, and optic tract, and a decline in visual function. The model recapitulates the key features of neurodegeneration in human glaucoma, which will facilitate and expedite the development of neuroprotective and neuroregenerative therapies.

Long-Term Intravitreal Dexamethasone Implant Outcomes in Uveitis

ABSTRACTPurpose: To describe the long-term clinical outcomes in a cohort of uveitic eyes treated with the intravitreal dexamethasone implant (Ozurdex; Allergan, Inc).Methods: Seventy-nine (63 patients) receiving 134 implant injections over 82 months were included. Indication, visual acuity (VA), intraocular pressure (IOP), vitreous haze score (VHS), central retinal thickness (CRT), time to reinjection, systemic treatments, and complications data were recorded.Results: The cumulative probability of VA improvement was 80% at 1 month and 90% at 12 months, and it was maintained until 60 months. Eyes with baseline vitritis (VHS >0.5; 68%) had a probability of VHS improvement of 33% at 1 month, 75% at 12 months, and 85% at 60 months. The probability of CRT improvement was 33% at 1 month, 75% at 12 months, and 85% at 60 months. The most frequent adverse event was moderate IOP elevation (≥25 mmHg) in 30.3%, no cases of retinal detachment or endophthalmitis were observed.Conclusions: The dexamethasone implant provides favorable VA, CRT, and VHS long-term outcomes in uveitis with a reduced rate of severe adverse events.

Hypertonie intraoculaire retardée liée aux injections intra-vitréennes répétées d’anti-VEGF : des cas nécessitant une chirurgie filtrante

We report cases of delayed, sustained elevated intraocular pressure (IOP) associated with repeated intravitreal anti-VEGF injections (IVI), which ultimately resulted in the need for filtering surgery. Two of the three cases demonstrated severe IOP elevation despite maximal medical treatment following unilateral IVI and required urgent filtering surgery. Optic nerve involvement was severe in all three cases. These intravitreal injections were performed for exudative age-related macular degeneration (AMD), and the patients did not show any sign of glaucoma or ocular hypertension prior to the initiation of treatment. Elevated IOP secondary to intravitreal steroids is a well-known side effect, as is immediate transient IOP elevation associated with anti-VEGF injection. Late, sustained IOP elevation after repeated injections of anti-VEGF, described approximately ten years ago, is often underestimated. Its incidence is estimated between 2.1% and 13% according to studies and increases with the number of IVI (cumulative effect). The pathophysiologic process is becoming increasingly understood, and several risk factors for this chronic IOP elevation have been identified. Most often, it is a moderate IOP elevation for which topical monotherapy is sufficient, or sometimes two, three or four medications or even selective laser trabeculoplasty (SLT). However, filtering surgery may rarely be required. Our findings illustrate a little-described phenomenon: a sudden, severe, late IOP elevation in response to anti-VEGF by an "overflow" effect, requiring urgent filtering surgery.

Late and sustained intraocular pressure elevation related to intravitreal anti-VEGF injections: Cases requiring filtering surgery

We report cases of delayed, sustained elevated intraocular pressure (IOP) associated with repeated intravitreal anti-VEGF injections (IVI), which ultimately resulted in the need for filtering surgery. Two of the three cases demonstrated severe IOP elevation despite maximal medical treatment following unilateral IVI and required urgent filtering surgery. Optic nerve involvement was severe in all three cases. These intravitreal injections were performed for exudative age-related macular degeneration (AMD), and the patients did not show any sign of glaucoma or ocular hypertension prior to the initiation of treatment. Elevated IOP secondary to intravitreal steroids is a well-known side effect, as is immediate transient IOP elevation associated with anti-VEGF injection. Late, sustained IOP elevation after repeated injections of anti-VEGF, described approximately ten years ago, is often underestimated. Its incidence is estimated between 2.1 % and 13 % according to studies and increases with the number of IVI (cumulative effect). The pathophysiologic process is becoming increasingly understood, and several risk factors for this chronic IOP elevation have been identified. Most often, it is a moderate IOP elevation for which topical monotherapy is sufficient, or sometimes two, three or four medications or even selective laser trabeculoplasty (SLT). However, filtering surgery may rarely be required. Our findings illustrate a little-described phenomenon: a sudden, severe, late IOP elevation in response to anti-VEGF by an "overflow" effect, requiring urgent filtering surgery.

New Developments in the Surgical Treatment of Glaucoma

In this review, we aimed to provide, in a structured format, an evidenced based review of the current state of minimally invasive surgical glaucoma management. Numerous studies, mostly non-comparative, have demonstrated several new, safe, effective, and minimally invasive surgeries for the management of various stages of open-angle glaucomas. These surgeries can either be combined with cataract surgery or performed in isolation of cataract surgery. Most of the newer minimally invasive procedures ensure safety with a mild to moderate intraocular pressure (IOP) lowering effect. Two novel shunts, the InnFocus MicroShunt and XEN45, however, can provide substantial IOP reduction in a relatively safe fashion. The future of glaucoma surgery is very bright, and there continue to be several safe, effective, and novel procedures for the management of various types of glaucomas.

Morphological and functional changes in the rat retina associated with 2 months of intermittent moderate intraocular pressure elevation

Morphological and functional changes in the rat retina and optic nerve head (ONH), associated with 8 weeks of intermittent moderately elevated intraocular pressure (IOP) were measured with a combined ultrahigh resolution optical coherence tomography (UHR-OCT) and electroretinography (ERG) system. The IOP of male Sprague-Dawley rats was raised in one eye to ~35 mmHg for 1 hour/day on 6 days each week using vascular loops. Single-flash ERG traces and volumetric UHR-OCT images of the ONH were acquired from both eyes before, during and after IOP elevations at weeks 1, 5 and 9 of the study. The UHR-OCT images showed depression of the posterior eye around the ONH during the IOP elevations, the magnitude of which increased significantly from week 1 to week 9 (p = 0.01). The ERG a-wave and b-wave amplitudes increased temporarily during IOP elevations and returned to normal ~30 minutes after loop removal. Recurrent intermittent IOP spikes caused > 30% decrease in the ERG a-wave and b-wave amplitudes measured during the IOP elevations over the course of 2 months. This study suggests that recurrent, relatively short-duration IOP spikes for extended period of time are associated with peri-ONH tissue hypercompliance and reduced retinal functional response to visual stimulation during acute IOP elevation.

Comparison of the iCare rebound tonometer and the Goldmann applanation tonometer.

Tonometry is a fundamental procedure in routine ophthalmologic examination. Although regarded as the reference standard, the Goldmann applanation tonometer (GAT) has its limitations. A new portable alternative to the GAT is the iCare rebound tonometer (RT). The aim of the present study was to compare the intraocular pressure (IOP) results obtained using the RT and GAT and then correlate the results with the central corneal thickness (CCT). Moreover, the tolerability and safety of the RT were evaluated. The IOP of 336 patients (672 eyes) was determined by the RT and GAT. The patients were divided into three groups (group A, 7–15 mmHg, n=74; group B, 16–22 mmHg, n=218; and group C, 23–50 mmHg, n=44), based on the GAT IOP readings. Pachymetry and slit lamp inspection were also performed. To establish an agreement between the devices, a Bland-Altman analysis and paired t-test were performed. The correlation between CCT and IOP readings obtained by the two devices were assessed using linear regression correlation analysis. The mean IOP values of the RT and the GAT were 18.30±5.10 and 18.52±4.46 mmHg, respectively. There were no significant differences between them (t=−1.31, P=0.19). The 95% confidence interval of the differences between the two devices was −5.80–6.24 mmHg. The RT readings are correlated well with those of GAT (r=0.806, P=0.001). However, the RT measurements were significantly (t=−2.84, P=0.007) lower (−1.66±3.87 mmHg) than those obtained with GAT when GAT ≥23 mmHg. Both the RT (r=0.390, P=0.001) and the GAT (r=0.191, P=0.001) showed positive correlations with CCT. The IOP measurement with RT was well tolerated. None of the corneal epithelial defects was detected and all subjects denied discomfort. The RT is well tolerated and safe, and can be considered a reliable alternative to GAT for patients in a low to moderate IOP range. However, in patients with high IOP values, the measurements obtained with RT did not correlate well with those obtained by GAT. The RT readings are influenced more by CCT compared to GAT.

Neuronal Release of Cytokine IL-3 Triggered by Mechanosensitive Autostimulation of the P2X7 Receptor Is Neuroprotective.

Mechanical strain due to increased pressure or swelling activates inflammatory responses in many neural systems. As cytokines and chemokine messengers lead to both pro-inflammatory and neuroprotective actions, understanding the signaling patterns triggered by mechanical stress may help improve overall outcomes. While cytokine signaling in neural systems is often associated with glial cells like astrocytes and microglia, the contribution of neurons themselves to the cytokine response is underappreciated and has bearing on any balanced response. Mechanical stretch of isolated neurons was previously shown to trigger ATP release through pannexin hemichannels and autostimulation of P2X7 receptors (P2X7Rs) on the neural membrane. Given that P2X7Rs are linked to cytokine activation in other cells, this study investigates the link between neuronal stretch and cytokine release through a P2X7-dependent pathway. Cytokine assays showed application of a 4% strain to isolated rat retinal ganglion cells (RGCs) released multiple cytokines. The P2X7R agonist BzATP also released multiple cytokines; Interleukin 3 (IL-3), TNF-α, CXCL9, VEGF, L-selectin, IL-4, GM-CSF, IL-10, IL-1Rα, MIP and CCL20 were released by both stimuli, with the release of IL-3 greatest with either stimuli. Stretch-dependent IL-3 release was confirmed with ELISA and blocked by P2X7R antagonists A438079 and Brilliant Blue G (BBG), implicating autostimulation of the P2X7R in stretch-dependent IL-3 release. Neuronal IL-3 release triggered by BzATP required extracellular calcium. The IL-3Rα receptor was expressed on RGCs but not astrocytes, and both IL-3Rα and IL-3 itself were predominantly expressed in the retinal ganglion cell layer of adult retinal sections, implying autostimulation of receptors by released IL-3. While the number of surviving ganglion cells decreased with time in culture, the addition of IL-3 protected against this loss of neurons. Expression of mRNA for IL-3 and IL-3Rα increased in rat retinas stretched with moderate intraocular pressure (IOP) elevation; BBG blocked the rise in IL-3, implicating a role for the P2X7R in transcriptional regulation in vivo. In summary, mechanical stretch triggers release of cytokines from neurons that can convey neuroprotection. The enhancement of these signals in vivo implicates P2X7R-mediated IL-3 signaling as an endogenous pathway that could minimize damage following neuronal exposure to chronic mechanical strain.

Survey of glaucoma surgical preferences and post-operative care in the United Kingdom.

To evaluate the spectrum of glaucoma surgery and the post-operative follow-up regimes undertaken among glaucoma specialists in the United Kingdom. National survey. Seventy-five glaucoma specialists (consultants and fellows). An eight-question survey was emailed to all glaucoma subspecialists members of the United Kingdom and Eire Glaucoma Society. Surgery undertaken, post-operative management, awareness of intervention tariff and handling of the follow-up burden generated through surgery. Almost all the participants (74/75: 99%) routinely performed trabeculectomy, 54 responders (72%) undertook tube surgery and Minimally Invasive Glaucoma Surgery (MIGS) was more frequently undertaken (33.0%) than non-penetrating surgery (23%). In general, for patients with advanced glaucoma requiring a low target intraocular pressure (IOP), the most frequent primary intervention was trabeculectomy (99%), followed by tubes (64%). Similarly, in patients with less advanced glaucoma requiring moderate target IOP, participants preferred trabeculectomy (99%), followed by MIGS (60%). By the first 6 months after the procedure, trabeculectomy and Baerveldt tube implant required a larger number of postoperative visits (9 and 7, respectively), than iStent® and non-penetrating deep sclerectomy (3 and 5, respectively). The majority of participants were not aware of the costs of their interventions. A wide variety of glaucoma surgery techniques are undertaken. Post-operative follow-up regimes are variable between techniques and for surgeons using the same technique. Trabeculectomy requires more follow-up than any other intervention. For patients requiring low IOP, trabeculectomy is the operation of choice for most surgeons.