Steroid-induced Ocular Hypertension Research Articles

Pilot study comparing a new virtual reality–based visual field test to standard perimetry in children

PurposeTo assess the feasibility and performance of Vivid Vision Perimetry (VVP), a new virtual reality (VR)–based visual field platform. MethodsChildren 7-18 years of age with visual acuity of 20/80 or better undergoing Humphrey visual field (HVF) testing were recruited to perform VVP, a VR-based test that uses suprathreshold stimuli to test 54 field locations and calculates a fraction seen score. Pearson correlation coefficients were calculated to evaluate correlation between HVF mean sensitivity and VVP mean fraction seen scores. Participants were surveyed regarding their experience. ResultsA total of 37 eyes of 23 participants (average age, 12.9 ± 3.1 years; 48% female) were included. All participants successfully completed VVP testing. Diagnoses included glaucoma (12), glaucoma suspect (7), steroid-induced ocular hypertension (3), and craniopharyngioma (1). Sixteen participants had prior HVF experience, and none had prior VVP experience, although 7 had previously used VR. Of the 23 HVF tests performed, 9 (39%) were unreliable due to fixation losses, false positives, or false negatives. Similarly, 35% of VVP tests were unreliable (as defined by accurate blind spot detection). Excluding unreliable HVF tests, the correlation between HVF average mean sensitivity and VVP mean fraction seen score was 0.48 (P = 0.02; 95% CI, 0.09-0.74). When asked about preference for the VVP or HVF examination, all participants favored the VVP, and 70% were “very satisfied” with VVP. ConclusionsIn our cohort of 23 pediatric subjects, VVP proved to be a clinically feasible VR-based visual field testing, which was uniformly preferred over HVF.

Steroid-Induced Ocular Hypertension in Mice Is Differentially Reduced by Selective EP2, EP3, EP4, and IP Prostanoid Receptor Agonists.

We tested five chemically and metabolically stable prostaglandin (PG) receptor agonists in a mouse model of dexamethasone-induced ocular hypertension (OHT). Whilst all compounds significantly (p < 0.05, ANOVA) lowered intraocular pressure (IOP) after twice-daily bilateral topical ocular dosing (5 µg/dose) over three weeks, the time course and magnitude of the responses varied. The onset of action of NS-304 (IP-PG receptor agonist) and rivenprost (EP4-PG receptor agonist) was slower than that of misoprostol (mixed EP2/EP3/EP4-PG receptor agonist), PF-04217329 (EP2-PG receptor agonist), and butaprost (EP2-PG receptor agonist). The rank order of IOP-lowering efficacies aligned with the onset of actions of these compounds. Peak IOP reductions relative to vehicle controls were as follows: misoprostol (74.52%) = PF-04217329 (74.32%) > butaprost (65.2%) > rivenprost (58.4%) > NS-304 (55.3%). A literature survey indicated that few previously evaluated compounds (e.g., latanoprost, timolol, pilocarpine, brimonidine, dorzolamide, cromakalim analog (CKLP1), losartan, tissue plasminogen activator, trans-resveratrol, sodium 4-phenyl acetic acid, etc.) in various animal models of steroid-induced OHT were able to match the effectiveness of misoprostol, PF-04217329 or butaprost. Since a common feature of the latter compounds is their relatively high affinity and potency at the EP2-PG receptor sub-type, which activates the production of intracellular cAMP in target cells, our studies suggest that drugs selective for the EP2-PG receptor may be suited to treat corticosteroid-induced OHT.

Baseline intraocular pressure: an independent risk factor in severe steroid-induced ocular hypertension after intravitreal dexamethasone implant.

To evaluate the baseline intraocular pressure (IOP)-related risk of severe steroid-induced ocular hypertension (SIOH). We hypothesized that the incidence and severity of SIOH may differ according to baseline IOP in patients who received intravitreal dexamethasone implants. A total of 889 eyes treated with intravitreal dexamethasone implants and a baseline IOP of ≤ 23mmHg were enrolled. Enrolled patients were divided into two groups: the steroid-responders(127 eyes) and the non-steroid-responders(762 eyes). The steroid-responders group was subdivided into post-injection IOP of ≥ 25, > 30, or > 35mmHg or IOP elevation of ≥ 10mmHg over the baseline value. The odds ratio of SIOH was calculated using univariable logistic regression analysis, and significant variables were analyzed with a multivariable model. IOP was measured before (baseline IOP) and after dexamethasone implant injection at 1week and 1, 2, 3, 6, and 12months. Although baseline IOP was significantly associated with the development of SIOH in logistic regression analysis, the results from the subgroup analysis differed. In the group with IOP elevation of ≥ 10mmHg over the baseline, SIOH was not significantly associated with baseline IOP, but it was significantly related to higher baseline IOP in the severe SIOH group (IOP > 30 and > 35mmHg). Higher baseline IOP is a risk factor for severe SIOH. Clinicians should be aware of the risk of SIOH when administering steroids intravitreally to patients with high baseline IOP (IOP > 19mmHg).

Gender-specific lncRNA-miRNA-mRNA regulatory network to reveal potential genes for primary open-angle glaucoma

BackgroundInvestigation of biomarkers may facilitate understanding the mechanisms of primary open-angle glaucoma (POAG) and developing therapeutic targets. This study aimed to identify potential genes based on competing endogenous RNA (ceRNA) network for POAG. MethodsBased on long noncoding RNAs (lncRNAs), microRNAs (miRNAs) and messenger RNAs (mRNAs) from the Gene Expression Omnibus (GEO) database, we identified differential expressed lncRNAs (DELs), differential expressed miRNAs (DEMis) and differential expressed mRNAs (DEMs) and then constructed a ceRNA network. Through weighted gene co-expression network analysis (WGCNA), we identified gender-specific genes for gender-associated ceRNA network construction, followed by the protein-protein interaction (PPI) network and functional enrichment analysis to screen hub genes and reveal their functions. The expression levels of hub genes were measured in steroid-induced ocular hypertension (SIOH) mice. ResultsA total of 175 DELs, 727 DEMs and 45 DEMis were screened between control and POAG samples. Seven modules were identified through WGCNA and one module was associated with gender of POAG patients. We discovered 41 gender-specific genes for gender-associated ceRNA construction and then identified 8 genes (NAV3, C1QB, RXRB, P2RY4, ADAM15, VAV3, ZNF207 and TOP1), which were enriched in cell cycle-related pathways and immune-related pathways. C1QB, RXRB, Top1 and ZNF207 were highly interacted with other proteins. The expression levels of NAV3 and C1QB were downregulated in SIOH, while the levels of RXRB, P2RY4, ADAM15, VAV3, ZNF207 and TOP1 were upregulated in SIOH. ConclusionThis study identifies hub genes associated with the pathogenesis of gender-specific POAG and provides potential biomarkers for POAG.

Hypertonie cortisonique tardive sous implants de dexaméthasone : à propos de 20 cas

Steroid-induced ocular hypertension (OHT) occurs in approximately one third of cases after dexamethasone implant (DEXi) injection. Among these, more than one fifth occur after the third DEXi intravitreal injection (IVI). Our goal was to analyze the clinical profiles of these late responders. A real-life, retrospective, observational study was conducted to assess demographic characteristics and intraocular pressure (IOP) responses in late responders (IOP ≥ 21mmHg, n DEXi ≥ 4). The following parameters were analyzed: IOP 2months after IVI and number of glaucoma medications needed. The IOP response compared to baseline was defined as low (< +6mmHg), moderate (≤ +15mmHg) or high (> 15mmHg). Late steroid-induced OHT occurred in 20.8% of cases. Twenty eyes (18patients) were included. The mean duration of follow-up was 3.8±1.9years. They received a mean number of 9.5±4.2IVI. The first OHT peak, measured at 25.3±3.2mmHg (21-31), occurred after 6.8±2.3IVI. Approximately 65% of OHT spikes occurred between the fourth and sixth IVI; 35% occurred later. At maximum, 1.7±1.0glaucoma medications and 0.75±0.79SLT procedures were required to control the OHT, with no filtering surgery required. The ratio of "low," "moderate," and "high" responders was 5%, 85% and 10% respectively. Late steroid-induced OHT occurs after at least 3DEXi in one fifth of multi-injected patients, requiring long-term IOP monitoring. This case series identifies mostly moderate responder profiles, whose IOP rise often remains well-controlled with medical management or laser treatment (SLT).

Steroid-Dependency in Posner-Schlossman Syndrome: A Suggested Topical 2% Ganciclovir and Gradual Decrement of Topical Steroid Combination Therapy from Shanghai PSS Study

ABSTRACT Purpose This study focused on the prevalence, unique features, and required treatment of steroid-dependent Posner-Schlossman syndrome (SD-PSS), and analyzed the outcome of 2% Ganciclovir and gradual decrement steroid combination therapy in SD-PSS patients. Methods Retrospective comparative and interventional study. SD-PSS was defined as PSS patients with continuous steroid use for over 3 months and relapsed within 2 weeks after steroid withdrawal or tapered dosage. Totally 74 SD-PSS eyes were compared with 78 randomly chosen non-steroid dependent PSS eyes. SD-PSS patients who underwent 2% GCV and gradual decrement steroid therapy with at least two follow-ups (n = 50) were analyzed for the treatment outcome. Results The prevalence of SD-PSS is 26.87% (97/361) in our PSS patients. SD-PSS patients demonstrated significantly younger onset age, longer disease course, higher intraocular pressure (IOP), and higher degree of iris depigmentation at the first visit. They required significantly more IOP-lowering medication and stronger steroid after the first visit. Our 2% GCV and gradual decrement steroid therapy helped 66% (33/50) SD-PSS patients with steroid withdrawal (median stable time: 13 weeks) and another 32% (16/50) SD-PSS managed to lower the dose or strength of topical steroid. Steroid-induced ocular hypertension happened in 5.26% (19/361) of the PSS patients. Conclusion Young onset age, high IOP, and high iris depigmentation level during acute stage are indicators of steroid dependency in PSS patients. SD-PSS patients require more medical surveillance. Two percent ganciclovir and gradual decrement steroid combination therapy help with steroid withdrawal and minimize steroid use.

Preclinical Evaluation of a Novel Once-a-Day Brimonidine Ophthalmic Nanosuspension.

Purpose: This article aims to describe a preclinical proof of concept for a novel once-a-day (OD) brimonidine ophthalmic nanosuspension. Methods: The preclinical proof of concept was established using New Zealand white rabbits as animal models. Dose-finding, multiple-dose efficacy, ocular pharmacokinetic, and hemodynamic studies were performed in normotensive rabbits. Steroid-induced ocular hypertension model in rabbits was used to study efficacy in glaucomatous pathophysiology. The test (0.35% OD suspension) and reference (0.15% three times a day [TID] solution) were compared. Results: The intraocular pressure (IOP) reduction was sustained for 0.35% and 0.5% strengths but not for other lower strengths tested or reference strengths. A 0.35% OD suspension reduced IOP >2 mmHg after 24 h of dosing, which was not seen with the reference. After multiple dosing, 0.35% OD suspension reduced IOP by 4-6 mmHg after 24 h, which was comparable to the 0.15% TID reference solution. An ocular pharmacokinetic study showed that the brimonidine was rapidly absorbed and distributed throughout the eye after topical administration. Concentration was higher in tissues with high α2 receptors, such as cornea-conjunctiva, iris/ciliary body, and choroid/retina. The steady-state concentrations in these organs were also significant after 24 h of the last dose. There was an indication of increased plasma levels, so a hemodynamic study was performed to assess any adverse effects. All hemodynamic parameters were normal and no new unusual safety findings were observed. Conclusions: The study demonstrated that the novel brimonidine 0.35% ophthalmic nanosuspension is both safe and effective when administered OD and is comparable to the marketed reference formulation administered TID.

Long-Term Risk of Steroid-Induced Ocular Hypertension/Glaucoma With Topical Prednisolone Acetate 1% After Descemet Stripping Endothelial Keratoplasty.

The aim of this study was to assess the long-term risk of steroid-induced ocular hypertension and the need for glaucoma treatment with long-term use of topical prednisolone acetate 1% in patients without preexisting glaucoma. We retrospectively reviewed the charts of 211 patients without previous glaucoma, who underwent Descemet stripping endothelial keratoplasty (DSEK) and used topical prednisolone acetate long-term to prevent graft rejection. Dosing was 4 times daily for 4 months and tapered to once daily. The main outcomes were ocular hypertension (defined as intraocular pressure ≥24 mm Hg, or increase of ≥10 mm Hg over baseline) and initiation of glaucoma treatment. The median patient age was 70 years (range: 34-94 years). The indications for DSEK were Fuchs dystrophy (88%), pseudophakic corneal edema (7%), failed DSEK (3%), and failed penetrating keratoplasty (2%). The median follow-up period was 7 years (range, 1-17 years). At 1, 5, and 10 years, the cumulative risks of steroid-induced ocular hypertension were 29%, 41%, and 49%, respectively, and the risks of requiring glaucoma treatment were 11%, 17%, and 25%, respectively. Among 35 eyes treated for glaucoma, 28 (80%) were managed medically and 7 (20%) had filtration surgery. Long-term use of potent topical corticosteroids, such as prednisolone acetate 1%, entails substantial risk of developing steroid-induced ocular hypertension, so frequent monitoring of intraocular pressure is required. With corneal transplantation, the risk can be mitigated by using techniques with a low inherent risk of rejection, such as Descemet membrane endothelial keratoplasty, whenever possible, to allow earlier reduction of steroid potency.

Association of trabecular meshwork height with steroid-induced ocular hypertension

It is important to identify at-risk patients prior to administering steroid injections to prevent avoidable irreversible blindness inducted by steroid-induced ocular hypertension (SIOH). We aimed to investigate the association of SIOH following intravitreal dexamethasone implantation (OZURDEX) using anterior segment optical coherence tomography (AS-OCT). We conducted a retrospective case control study to assess the association between trabecular meshwork and SIOH. A total of 102 eyes that underwent both AS-OCT and intravitreal dexamethasone implant injection were divided into the post-steroid ocular hypertension and normal intraocular pressure groups. Ocular parameters that can contribute to intraocular pressure were measured using AS-OCT. Univariable logistic regression analysis was used to calculate the odds ratio of the SIOH and significant variables were further analyzed using a multivariable model. Trabecular meshwork (TM) height was significantly shorter in the ocular hypertension group (716.13 ± 80.55 μm) than that in the normal intraocular pressure group (784.27 ± 82.33 μm) (p < 0.001). The receiver operating characteristic curve technique analysis showed that the optimal cut-off of ≥ 802.13 μm for TM height specificity was 96.2%, and TM height with < 646.75 μm had a sensitivity of 94.70%. The odds ratio of the association was 0.990 (p = 0.001). TM height was identified as a newly observed association with SIOH. TM height can be assessed using AS-OCT, with acceptable sensitivity and specificity. Caution must be exercised while injecting steroids in patients with short TM height (especially < 646.75 μm) as it may cause SIOH and irreversible blindness.

Incidence and risk factors of steroid-induced ocular hypertension following pterygium excision with conjunctival autograft

Background: Topical steroids are used to reduce post-operative inflammation after ocular surgery with the potential risk of ocular hypertension, glaucoma and blindness. There is a paucity of published data globally and locally on steroid-induced ocular hypertension (SiOH) post pterygium excision(PE) with conjunctival autograft (CAG). Objective: We aimed to determine the incidence and risk factors of SiOH post-PE with CAG in Korle-Bu Teaching Hospital, Accra, Ghana. Methods: In this prospective observational study, the demographic and clinical data of patients undergoing PE with CAG were collected and analyzed. Post-operative intraocular pressures (IOP) were measured on days 1, 7, 14, 28, and 42. The cumulative incidence of SiOH (proportion of the increase in IOP ≥10mmHg at six weeks compared to baseline) and mean change in IOP from baseline were computed. Risk factors of SiOH were determined using a multiple logistic regression model. The Kaplan-Meier survival curve was used in estimating the median time to develop SiOH. Results: Overall, 101 patients participated in this study with a mean age of 46.8±11.9 years. The majority (65.3%, n= 66/101) of participants were females. The mean pre-operative IOP in the study eyes was 15.3±3.0 mmHg. The overall mean post-operative IOP was 18.6±2.8 mmHg (p= 0.001). The overall incidence of SiOH six weeks post-PE with CAG was 32.7% (95% confidence interval (CI)= 23.7-42.7%). Male sex was the only independent factor associated with the development of SiOH [odds ratio (OR) = 3.3; 95% CI = 1.1-9.7; p= 0.032]. The median time to develop SiOH was 42 days (95% CI= 37.1-46.9 days, p= 0.022). Conclusion: The study showed that SiOH post-PE is a common complication with an overall six-weeks post-excision incidence of 32.7%. Males are more likely to develop SiOH after PE with CAG. Patients undergoing PE with CAG should be closely monitored postoperatively to prevent complications associated with prolonged raised IOP.

Rho Kinase Inhibitor AR-12286 Reverses Steroid-Induced Changes in Intraocular Pressure, Effective Filtration Areas, and Morphology in Mouse Eyes.

We investigated mechanisms of reduction of intraocular pressure (IOP) by Rho kinase inhibitor AR-12286 in steroid-induced ocular hypertension (SIOH). C57BL/6 mice (N = 56) were randomly divided into Saline, dexamethasone (DEX), DEX + AR-12286, and DEX-discontinuation (DEX-DC) groups. IOP was measured weekly during the first four weeks in all groups. Beginning at week 5, the DEX-DC group was followed without treatment until IOP returned to normal, and the other groups were treated as assigned with IOP measured every other day for another week. Fluorescent tracer was injected into the anterior chamber to visualize the outflow pattern in the trabecular meshwork (TM) and TM effective filtration area (EFA) was determined. Radial sections from both high- and low-tracer regions were processed for electron microscopy. AR-12286 reduced IOP in SIOH mouse eyes in one day (P < 0.01). At the end of week 5, mean IOP in the DEX + AR-12286 group was ∼4 mm Hg lower than DEX group (P < 0.001) and ∼2 mm Hg lower than DEX-DC group (P < 0.05). After one-week AR-12286 treatment (P < 0.05) or five-week DC of DEX (P < 0.01), DEX-induced reduction of EFA was rescued and DEX-induced morphological changes in the TM were partially reversed. AR-12286 reversed steroid-induced morphological changes in the TM and reduced EFA, which correlated with reduced IOP in SIOH eyes. AR-12286 reduced IOP elevation in SIOH eyes more effectively than discontinuing DEX treatment even when accompanied by continuous DEX treatment. Therefore Rho kinase inhibitors may lower SIOH in patients who rely on steroid treatment.

Metformin protects trabecular meshwork against oxidative injury via activating integrin/ROCK signals.

This study aimed to investigate the protective effect of metformin on trabecular meshwork (TM) and explore its molecular mechanisms in vivo and in vitro. Ocular hypertension (OHT) mouse models were induced with dexamethasone and further treated with metformin to determine the intraocular pressure (IOP)-lowering effect. Cultured human TM cells (HTMCs) were pre-stimulated with tert-butyl hydroperoxide (tBHP) to induce oxidative damage and then supplemented with metformin for another 24 hr. The expression of fibrotic markers and integrin/Rho-associated kinase (ROCK) signals, including α-smooth muscle actin (α-SMA), transforming growth factor-β (TGF-β), fibronectin, integrin beta 1, ROCK 1/2, AMP-activated protein kinase, myosin light chain 1, and F-actin were determined by western blotting and immunofluorescence. Reactive oxygen species (ROS) content was analysed using flow cytometry. Transmission electron microscopy was performed to observe microfilaments in HTMCs. It showed that metformin administration reduced the elevated IOP and alleviated the fibrotic activity of aqueous humour outflow in OHT models. Additionally, metformin rearranged the disordered cytoskeleton in the TM both in vivo and in vitro and significantly inhibited ROS production and activated integrin/ROCK signalling induced by tBHP in HTMCs. These results indicated that metformin reduced the elevated IOP in steroid-induced OHT mouse models and exerted its protective effects against oxidative injury by regulating cytoskeleton remodelling through the integrin/ROCK pathway. This study provides new insights into metformin use and preclinical evidence for the potential treatment of primary open-angle glaucoma.

Systemic steroid-induced ocular hypertension in a 7-year-old child with nephrotic syndrome and its management with netarsudil 0.02% eye drop

Prolonged use of corticosteroids may lead to increase in intraocular pressure (IOP), termed as steroid-induced ocular hypertension (SIOH). We report a case of a 7-year-old child with nephrotic syndrome and SIOH, uncontrolled with latanoprost 0.05%. Netarsudil 0.02%, a Rho kinase (ROCK) inhibitor, controlled IOP despite continuing steroid treatment and was tolerated well. Review of literature revealed ROCK inhibitors may be efficacious antiglaucoma medicines for SIOH owing to their direct action on corticosteroid-affected conventional aqueous outflow pathway. To the best of our knowledge, this is the first case report documenting the role of ROCK inhibitors in the management of pediatric SIOH.

Whole-genome sequencing unravels novel genetic determinants and regulatory pathways associated with triamcinolone acetonide-induced ocular hypertension.

Glucocorticosteroids commonly used to treat certain ocular inflammatory conditions cause an unwarranted elevation in intraocular pressure (IOP) leading to steroid-induced ocular hypertension (OHT). This study aims to identify novel genetic variants in the Indian population associated with steroid responsiveness, specifically to that of intravitreal Triamcinolone acetonide (TA) injections, which leads to OHT in 27% of the TA-treated Indian subjects. Genetic determinants and pathways regulating TA-OHT progression were investigated by applying whole-genome sequencing (WGS) on DNA extracted from 53 blood samples that included TA responders and non-responders. Sequencing analysis yielded 45 intronic and 49 exonic variants to be associated with TA-OHT, which are known to play a vital role in eye, heart, brain, and bone deformities. Of these, the most significant genetic variant associated with TA-OHT was further considered for molecular dynamics (MD) simulation studies. Variants in the CRPPA, PLOD1, ARHGAP1, TIMELESS and TNFSF4 genes were found to be directly implicating TA-OHT. Furthermore, these genes were enriched in pathways associated with cardiomyopathy, focal adhesion, extracellular matrix, and actin cytoskeleton reorganization. MD simulation studies revealed that the top significant variant (rs141625803) in the CRPPA gene possesses a high pathogenic and structurally destabilizing effect. Thus, novel genetic variants that could be significantly associated with the TA-OHT progression were identified in this study. Validation of these targets in a larger cohort of patients along with their functional analysis would inform on the disease, thereby adding to the existing knowledge on the pathophysiology of TA-OHT.

Selective laser trabeculoplasty for steroid-induced ocular hypertension following endothelial keratoplasty.

Purpose: To examine the safety and efficacy of selective laser trabeculoplasty (SLT) in patients responding to topical steroids with elevated intraocular pressure following endothelial keratoplasty. Methods: Patients that underwent Descemet Membrane Endothelial Keratoplasty (DMEK) or Descemet Stripping Automated Endothelial Keratoplasty (DSAEK) were offered SLT as first-line therapy if they presented with steroid response and met inclusion criteria. Patient demographics, best-corrected visual acuity (BCVA), steroid and glaucoma regimens were recorded before and after SLT. Results: Twelve eyes of 8 patients were recruited to the study. All patients demonstrated a reduction in IOP and only one patient remained on anti-glaucoma drops after SLT. The mean (±SD) reduction in IOP following SLT was 8.8 (±4.9) mmHg (p < 0.0001). BCVA remained stable and no adverse events following treatment were observed. Conclusions: SLT may be a safe and effective treatment option that reduces topical antihypertensive burden while allowing continuance of corticosteroids in steroid-responsive eyes at high risk of rejection following endothelial keratoplasty. Larger randomized studies are needed to compare SLT efficacy with topical medication in this patient group and to review any impact on graft survival and glaucoma progression.

Demographic and clinical features of pediatric uveitis and scleritis at a tertiary referral center in China

BackgroundTo analyse demographic, clinical features, treatment and therapeutic outcomes of pediatric uveitis and scleritis patients.SubjectsThe clinical records of pediatric uveitis and scleritis cases between January 2012 and December 2020 at a tertiary uveitis service center in Tianjin Medical University Eye Hospital (TMUEH) were reviewed.ResultsIn total, 209 patients (337 eyes) were included, 49.3% were male. The median onset age was 9.0 (IQR, 7.0–12.0) years. Chronic uveitis and scleritis accounted for 86.1%. Panuveitis (29.2%), anterior uveitis(29.2%), and intermediate uveitis (22.0%) were the most common presentations. The most common diagnoses were idiopathic (71.3%), JIA (8.1%), and infectious uveitis (4.8%). At baseline, 40.7% patients received oral corticosteroid therapy; during follow-up, corticosteroids (66.0%), disease-modifying antirheumatic drugs (61.2%), and biologic agents (35.4%) were the mainstay. Posterior synechia (26.1%) and cataracts (25.5%) were the most common complications. In acute cases, the median best corrected visual acuity (BCVA) was 0.99 (IQR, 0.5–1.0) at baseline and 0 (IQR, 0–0) at last follow-up; in chronic cases, the median BCVA improved from 1.09 (IQR, 0.5–2.0) to 0.27 (IQR, 0–0.5), with anterior chamber cell grade significantly declining. Ten eyes underwent cataract surgery during regular follow-up and achieved satisfactory long-term visual outcomes and decreased burden of immunosuppressants. The incidence of steroid-induced ocular hypertension was 41.0%, and children with frequent instillation of eyedrops were at high risk.ConclusionsMost cases were of chronic uveitis and scleritis requiring long-term systemic immunosuppressive therapies in pediatric uveitis and scleritis in China. Good management of complications is important for long-term prognosis.

Intravitreal dexamethasone versus bevacizumab in Aboriginal and Torres Strait Islander patients with diabetic macular oedema: The OASIS study (a randomised control trial).

Frequent intravitreal anti-VEGF injections are impractical for many Aboriginal patients with diabetic macular oedema (DMO). The longer acting intravitreal dexamethasone implant (DEX-implant) is approved for DMO but has not been assessed in an Aboriginal population. This was a prospective, multicentre, randomised, single-masked, non-inferiority clinical trial. Aboriginal adults from Western Australia with DMO were randomised to receive 3-monthly DEX-implant, or monthly intravitreal bevacizumab. The primary outcome was the change in best corrected visual acuity (BCVA) at 12 months. The final endpoint was analysed for 24 DEX-implant and 28 bevacizumab injection eyes. Mean BCVA improved by 4.0 letters (-0.08 LogMAR) in the DEX-implant group and worsened by 5.5 letters (0.11 LogMAR) in the bevacizumab group. Before adjusting for cataract surgery, the upper bound of the two-sided 90% CI for the DEX-implant was 3.5 letters (0.07 LogMAR), which met non-inferiority criteria. The BCVA of remote participants who received the DEX-implant improved by 5.5 letters (0.11 LogMAR), compared to an 18.5 letter (0.37 LogMAR) decline for bevacizumab (p= 0.04). The incidence of steroid-induced ocular hypertension for the DEX-implant was 33.3%. Before adjusting for the effect of cataract surgery, the DEX-implant was non-inferior to bevacizumab for treating DMO in Aboriginal participants. In remote participants, the DEX-implant surpassed non-inferiority to achieve superior outcomes to bevacizumab. The incidence of steroid-induced hypertension was comparable to that reported in non-Aboriginal populations. We provide guidelines for the judicious use of DEX-implant among Aboriginal people, and a framework for performing ophthalmic clinical trials in Aboriginal communities.

Glaucoma and risk factors three years after congenital cataract surgery

BackgroundThis study aimed to identify the incidence of and risk factors for postoperative glaucoma-related adverse events at various time points after congenital cataract surgery.MethodsThis retrospective cohort study enrolled 259 eyes from 174 patients (surgical age ≤ 7 years) who underwent congenital cataract surgery. All surgical procedures were conducted at the Eye Hospital of Wenzhou Medical University between May 2011 and March 2019. Patients were classified into group 1 [primary intraocular lens (IOL) implantation, N = 111 eyes], group 2 (secondary IOL implantation, N = 85 eyes), and group 3 (no IOL implantation, N = 63 eyes). We recorded demographic factors and incidence and risk factors for glaucoma-related adverse events.ResultsGlaucoma-related adverse events occurred in 21 (8.1%) eyes, whereas 27 (10.4%) eyes developed steroid-induced ocular hypertension. The percentage of glaucoma-related adverse events was 0%, 1.2%, 1.2%, 1.6%, 4.0%, and 8.9% at 1 month, 6 months, 1 year, 2 years, 3 years and 4 years after surgery, respectively. Sixteen (18.8%), five (7.9%), and zero eyes developed glaucoma-related adverse events in groups 2, 3, and 1, respectively. Family history of congenital cataract [hazard ratio (HR), 50.463; 95% confidence interval (CI), 7.051–361.139; P < 0.001], preoperative central corneal thickness (CCT) [HR, 1.021; 95% CI, 1.009–1.034; P = 0.001], preoperative horizontal corneal diameter (HCD) [HR, 3.922; 95% CI, 1.558–9.804; P = 0.004], and preoperative lens thickness (LT) [HR, 3.745; 95% CI, 1.344–10.417; P = 0.012] were identified as predictors of postoperative glaucoma-related adverse events.ConclusionsFamily history of congenital cataract, thicker preoperative CCT, smaller preoperative HCD, and thinner preoperative LT are the main risk factors of postoperative glaucoma-related adverse events. Regular monitoring of children after cataract surgery with these risk factors may help ophthalmologists detect susceptible individuals and provide timely interventions in the clinic.

Effect of ATP-sensitive Potassium Channel Openers on Intraocular Pressure in Ocular Hypertensive Animal Models.

PurposeTo evaluate the effect of ATP-sensitive potassium channel openers cromakalim prodrug 1 (CKLP1) and diazoxide on IOP in three independent mouse models of ocular hypertension.MethodsBaseline IOP was measured in TGFβ2 overexpression, steroid-induced, and iris dispersion (DBA/2J) ocular hypertension mouse models, followed by once daily eyedrop administration with CKLP1 (5 mM) or diazoxide (5 mM). The IOP was measured in conscious animals with a handheld rebound tonometer. Aqueous humor dynamics were assessed by a constant perfusion method. Effect of treatment on ocular tissues was evaluated by transmission electron microscopy.ResultsCKLP1 decreased the IOP by 20% in TGFβ2 overexpressing mice (n = 6; P < 0.0001), 24% in steroid-induced ocular hypertensive mice (n = 8; P < 0.0001), and 43% in DBA/2J mice (n = 15; P < 0.0001). Diazoxide decreased the IOP by 32% in mice with steroid-induced ocular hypertension (n = 13; P < 0.0001) and by 41% in DBA/2J mice (n = 4; P = 0.005). An analysis of the aqueous humor dynamics revealed that CKLP1 decreased the episcleral venous pressure by 29% in TGFβ2 overexpressing mice (n = 13; P < 0.0001) and by 72% in DBA/2J mice (n = 4 control, 3 treated; P = 0.0002). Diazoxide lowered episcleral venous pressure by 35% in steroid-induced ocular hypertensive mice (n = 3; P = 0.03). Tissue histology and cell morphology appeared normal when compared with controls. Accumulation of extracellular matrix was reduced in CKLP1- and diazoxide-treated eyes in the steroid-induced ocular hypertension model.ConclusionsATP-sensitive potassium channel openers CKLP1 and diazoxide effectively decreased the IOP in ocular hypertensive animal models by decreasing the episcleral venous pressure, supporting a potential therapeutic application of these agents in ocular hypertension and glaucoma.

The occurrence timeline of steroid-induced ocular hypertension and cataract in children with systemic autoimmune diseases.

Steroid-induced ocular hypertension (SIOH) and cataract can result in visual loss. This study evaluated the timetable of SIOH and steroid-induced posterior subcapsular cataract (SI-PSC) occurrences in children with systemic autoimmune diseases (SAD) undergoing long-term systemic corticosteroid treatment. Thirty-seven children with SAD treated with long-term oral corticosteroids were enrolled in this study. Intraocular pressure (IOP), SI-PSC occurrences, visual field and peripapillary retinal nerve fibre layer (pRNFL) thicknesses were recorded every 3months for at least 6months. Of the 37 children, with average age 11.0 ± 2.9years, 22 patients (59.5%) had SIOH, 2 progressed as glaucoma at the 18-month and 3-year follow-up, respectively, and 12 (32.4%) patients had SI-PSC. Among patients with SIOH, 45.5% (10/22) of them had SI-PSC occurrence, and among patients with normal IOP, 13.3% (2/15) of them had SI-PSC. Seventeen patients participated in a longitudinal study with a follow-up period of at least 18months. The incidence of SIOH started at 1month 52.9% (9/17) and gradually increased to 70.6% (12/17) at 6months, then decreased to 35.3% (6/17). SI-PSC onset started at 6months (17.6%, 3/17), and its occurrence increased to 35.3% (6/17) at 12months and reached to 41.2% (7/17) at 18months. The pRNFL was thicker in the children with SIOH than the healthy controls (p = 0.01). SIOH and SI-PSC are common coexistent complications in children with long-term corticosteroids treatment, and the occurrence time is during the first month and 6months, respectively. Patients with SIOH have a higher probability of cataract.