Steroid-induced Glaucoma Research Articles

In Vivo Models of Steroid-Induced Intraocular Hypertension

Corticosteroids are widely utilized for their anti-inflammatory and immunosuppressive properties but often lead to ocular complications, including ocular hypertension. If untreated, ocular hypertension can progress to optic nerve atrophy and eventually result in steroid-induced glaucoma, which poses a risk of irreversible visual damage. Approximately 40% of individuals experience increased intraocular pressure after steroid use, and around 6% develop glaucoma. Although steroid-induced glaucoma is usually temporary and reversible if the treatment duration is under a year, prolonged exposure can cause permanent vision impairment. The pathogenesis of steroid-induced glaucoma is suggested to arise from increased outflow resistance of aqueous humor, primarily due to decreased expression of matrix metalloproteinases. This deficiency promotes the deposition of extracellular matrix and the dysfunction of trabecular meshwork cells. Additionally, modifications in the actin cytoskeleton increase the stiffness and alter the morphology of trabecular meshwork, further impeding aqueous humor outflow. Molecular changes, such as elevated expression of the MYOC gene, have also been implicated in restricting aqueous outflow. Various animal models, including rats, mice, primates, rabbits, cattle, sheep, cats, and dogs, have been developed to study steroid-induced glaucoma. These models exhibit pathological, pathophysiological, and molecular similarities to human disease, making them valuable for research. This review aims to summarize common animal models of steroid-induced ocular hypertension, discussing their advantages and limitations. The goal is to help researchers select appropriate models for future studies, thereby advancing the understanding of disease mechanisms and developing preventive strategies.

The Delayed Turnover of Proteasome Processing of Myocilin upon Dexamethasone Stimulation Introduces the Profiling of Trabecular Meshwork Cells' Ubiquitylome.

Glaucoma is chronic optic neuropathy whose pathogenesis has been associated with the altered metabolism of Trabecular Meshwork Cells, which is a cell type involved in the synthesis and remodeling of the trabecular meshwork, the main drainage pathway of the aqueous humor. Starting from previous findings supporting altered ubiquitin signaling, in this study, we investigated the ubiquitin-mediated turnover of myocilin (MYOC/TIGR gene), which is a glycoprotein with a recognized role in glaucoma pathogenesis, in a human Trabecular Meshwork strain cultivated in vitro in the presence of dexamethasone. This is a validated experimental model of steroid-induced glaucoma, and myocilin upregulation by glucocorticoids is a phenotypic marker of Trabecular Meshwork strains. Western blotting and native-gel electrophoresis first uncovered that, in the presence of dexamethasone, myocilin turnover by proteasome particles was slower than in the absence of the drug. Thereafter, co-immunoprecipitation, RT-PCR and gene-silencing studies identified STUB1/CHIP as a candidate E3-ligase of myocilin. In this regard, dexamethasone treatment was found to downregulate STUB1/CHIP levels by likely promoting its proteasome-mediated turnover. Hence, to strengthen the working hypothesis about global alterations of ubiquitin-signaling, the first profiling of TMCs ubiquitylome, in the presence and absence of dexamethasone, was here undertaken by diGLY proteomics. Application of this workflow effectively highlighted a robust dysregulation of key pathways (e.g., phospholipid signaling, β-catenin, cell cycle regulation) in dexamethasone-treated Trabecular Meshwork Cells, providing an ubiquitin-centered perspective around the effect of glucocorticoids on metabolism and glaucoma pathogenesis.

Corticosteroid-induced Glaucoma: An avoidable blindness

Healthcare professionals frequently advise the use of topical steroid eye drops to manage and control postoperative inflammation following phacoemulsification. Although there are many benefits associated with steroid usage, it is imperative to recognize the potential negative repercussions that may arise. In individuals who respond to steroids, the use of topical steroid drops can lead to an increase in intraocular pressure (IOP). Increase in IOP resulting from the side effects of steroids typically manifests several weeks following the initiation of eye drop therapy. The first documentation of steroid induced glaucoma (SIG) can be traced back to the 1950s on the administration of systemic adrenocorticotropic hormones. The elevation of IOP is a complex issue influenced by various factors, but the primary factor is the increased resistance within the outflow mechanisms of the trabecular meshwork. Out of all the risk factors related to ocular hypertension caused by steroid use, a preexisting glaucoma diagnosis is the most frequently seen. The usage of different routes of steroids administration has been linked to the occurrence of ocular hypertension. The current management approach prioritizes the exploration of steroid-sparing treatment options, discontinuing steroid use, employing medications to lower intraocular pressure, and considering interventional laser and surgical procedures.

Influence of dexamethasone-induced matrices on the TM transcriptome

Pathologic bidirectional interactions between the extracellular matrix (ECM) and cells within the human trabecular meshwork (hTM) contribute to ocular hypertension. An in vitro model is needed to study these cell-matrix interactions and their effect on outflow homeostasis. This study aimed to determine whether pathogenic ECM derived from dexamethasone (DEX)-treated hTM cultures induces clinically relevant glaucoma-like changes in healthy hTM cells at the transcriptional level. Corneoscleral rims from non-glaucoma donors were used to isolate primary hTM cells after validation according to the consensus recommendations for TM culture. Normal hTM cells (n = 5) were plated on a coverslip and treated with 100 nM DEX or ethanol for four weeks. These cultures were then decellularized, plated with primary hTM cells, and allowed to grow for another 72 h. RNA was extracted from these hTM cells for stranded total RNA-Seq. Sequencing libraries prepared using the Zymo-Seq RiboFree Total RNA library kit were pooled and sequenced using Illumina NovaSeq 6000. After quality control, sequence reads were aligned to the human genome build hg19. Differential expression (DE) analyses were performed using paired multi-factorial ANOVA. The expression of several DE genes associated with glaucoma (ANGPTL2, PDE7B, C22orf23, COL4A1, ADAM12, IFT122, SEMA6C) was validated using EvaGreen-based Droplet Digital PCR (ddPCR) assays. Gene ontology analyses of the DE genes were performed using the PANTHER and NDEx IQA databases, and functional analyses were performed with the DAVID Bioinformatics software. Using a cutoff of p-value <0.05 and fold change ≥2.0, our differential analysis identified 267 up- and 135 down-regulated genes in DEX-induced ECM-treated cells compared to the control. These differentially expressed genes were found to play a significant role in pathways such as cytokine and oxidative stress-induced inflammation, integrin signaling, matrix remodeling, and angiogenesis. These findings were further supported by previously performed proteomics studies using the same model. Using ddPCR, we validated the expression of seven genes associated with the risk of primary open-angle glaucoma. These results not only provide support for the pathogenic ECM model of steroid-induced glaucoma, but also demonstrate that the pathologic changes induced by this model are indeed found at the transcriptional level. These findings further demonstrate that matrix changes significantly influence cell expression profiles, which enable further understanding of the molecular mechanisms underlying glaucomatous changes in the TM. However, future studies with a larger and more diverse set of samples and longer time points are needed to confirm the utility of this model for mechanistic studies.

Suspicious eyes - Elvis's glaucoma battle.

Elvis Presley (1935-1977) is an iconic figure in modern pop culture. Although many of his medical conditions have been the subject of extensive speculation, less is known about his ophthalmological problems, including steroid-induced glaucoma caused by a life-long use of steroids, both prescribed and self-administered, and secondary angle closure glaucoma most likely due to anterior uveitis. Further, he had an episode of acute angle closure glaucoma in 1971 that was treated with a subconjunctival injection of a mydriatic agent or, less likely, a paracentesis combined with an iridotomy. David Meyer, MD, was Presley's main ophthalmologist from 1971 until the latter's death in 1977.

Modified viscotrabeculotomy versus modified trabeculotomy in late-onset primary congenital, juvenile, and secondary open-angle glaucoma.

To compare modified viscotrabeculotomy (VCO-Tbo) to modified trabeculotomy (Tbo) in late-onset primary congenital, juvenile open-angle, steroid-induced, and pigmentary glaucoma. Patients were randomly assigned to VCO-Tbo and Tbo groups in this study. Intraocular pressure (IOP), antiglaucoma medications, and success/failure rates were assessed. A linear mixed model was used to compare the change trend at different follow-up times. Survival time was evaluated using the Kaplan-Meier graph and Log-Rank test. The mean IOP at 1, 3, and 12 months in the VCO-Tbo group was 14.1 ± 3.1, 15.9 ± 3 and 17 ± 3.1 mmHg, respectively. The mean IOP at the same time points in the Tbo group was 15.9 ± 3.3, 17.6 ± 3.5 and 18.4 ± 3.2 mmHg (P = 0.051, 0.058, 0.088, respectively). The VCO-Tbo group had significantly lower IOP after six months (16.5 ± 4.1 mmHg vs. 18.7 ± 3.8 mmHg; p = 0.031) and by the last visit (16.8 ± 2.1 mmHg vs. 18.8 ± 2 mmHg; p = 0.013). The reduction in the number of medications was significant in both groups compared to baseline (P < 0.001), but there was no significant difference between groups (P = 0.450). The complete and qualified success rate was 43.9% and 34.1% in the VCO-Tbo group and 46.8% and 10.6% in the Tbo group at the final follow-up (p = 0.040, and 0.039, respectively). Both procedures are effective in IOP and medication reduction. The survival time and efficacy of modified trabeculotomy can be augmented by injecting cohesive viscoelastic in the Schlemm's canal.

Differential Effects of Benzalkonium Chloride on Human Trabecular Meshwork Cells Not Treated or Treated with Transforming Growth Factor-β2 or Dexamethasone.

Purpose: The objective of the present study was to evaluate the effects of low concentrations of benzalkonium chloride (BAC) (10-7%, 10-6%, or 10-5%) on healthy and glaucomatous human trabecular meshwork (HTM) cells. For this purpose, we used in vitro models replicating a healthy HTM and HTM with primary open-angle glaucoma (POAG) or steroid-induced glaucoma (SG) using two-dimensional (2D) cultures of HTM cells not treated or treated with a 5 ng/mL solution of transforming growth factor-β2 or 250 nM dexamethasone (DEX). Methods: Analyses were carried out for (1) the intercellular affinity function of 2D HTM monolayers, as determined by transepithelial electrical resistance (TEER) measurements; (2) cell viability; (3) cellular metabolism by using a Seahorse bioanalyzer; and (4) expression of extracellular matrix (ECM) molecules, an ECM modulator, and cell junction-related molecules. Results: In the absence and presence of BAC (10-7% or 10-5%), intercellular affinity function determined by TEER and cellular metabolic activities were significantly and dose dependently affected in both healthy and glaucomatous HTM cells despite the fact that there was no significant decrease in cell viabilities. However, the effects based on TEER values were significantly greater in the healthy HTM. The mRNA expression of several molecules that were tested was not substantially modulated by these concentrations of BAC. Conclusions: The findings reported herein suggest that low concentrations of BAC may have unfavorable adverse effects on cellular metabolic capacity by inducing increases in the intercellular affinity properties of the HTM, but those effects of BAC were different in healthy and glaucomatous HTM cells.

Immune Analysis Using Vitreous Optical Coherence Tomography Imaging in Rats with Steroid-Induced Glaucoma.

Glaucoma is a multifactorial pathology involving the immune system. The subclinical immune response plays a homeostatic role in healthy situations, but in pathological situations, it produces imbalances. Optical coherence tomography detects immune cells in the vitreous as hyperreflective opacities and these are subsequently characterised by computational analysis. This study monitors the changes in immunity in the vitreous in two steroid-induced glaucoma (SIG) animal models created with drug delivery systems (microspheres loaded with dexamethasone and dexamethasone/fibronectin), comparing both sexes and healthy controls over six months. SIG eyes tended to present greater intensity and a higher number of vitreous opacities (p < 0.05), with dynamic fluctuations in the percentage of isolated cells (10 µm2), non-activated cells (10-50 µm2), activated cells (50-250 µm2) and cell complexes (>250 µm2). Both SIG models presented an anti-inflammatory profile, with non-activated cells being the largest population in this study. However, smaller opacities (isolated cells) seemed to be the first responder to noxa since they were the most rounded (recruitment), coinciding with peak intraocular pressure increase, and showed the highest mean Intensity (intracellular machinery), even in the contralateral eye, and a major change in orientation (motility). Studying the features of hyperreflective opacities in the vitreous using OCT could be a useful biomarker of glaucoma.

Virna Glaucoma Drainage Device Implantation On Pediatric Patient With Steroid Induced Glaucoma

Introduction : Steroid-induced Glaucoma (SIG) in pediatric patient is reported to have a more progressive and severe manifestations often unresponsive to glaucoma filtration surgery. We aim to report a successful management of SIG using Virna implant on pediatric patient.&#x0D; Case Illustration : A 10 years old boy underwent bilateral Virna GDD implantation following uncontrollable IOP after multiple trabeculectomies. The patient presented with a UCVA of 4/60 on both eyes. IOP of RE and LE is 31.8 mmHg and 29.7 mmHg respectively with four anti-glaucoma medications. Both eyes revealed conjunctival hyperemia with no bleb formation, VH3 AC, 12 o’clock iridectomy, C/D ratio of 0.9 with bayonet sign and nasalization on indirect funduscope, open angle on gonioscope, annular scotoma on Humphrey, and diffuse thinning of RNFL on OCT. Six months postoperatively, BCVA of RE and LE is 6/60 and 6/30 respectively with minimal progression on both ocular visual field defects. As for IOP, RE IOP is 18.7 mmHg with two anti-glaucoma medications and LE IOP is 14.3 mmHg without anti-glaucoma medications.&#x0D; Discussion : Multiple failed trabeculectomies is an indication for GDD. Virna implants are meant for adult subsequently making plate and tube placement crucial in pediatric patient because the globe is still growing and relatively thin. It is necessary to evaluate IOP periodically after implantation as IOP will enter hypertensive phase and stabilize in 3-6 months.&#x0D; Conclusion : GDD implantation, including Virna Implant, is a viable alternative to children with refractory SIG to prevent further glaucomatous damage.

Microinvasive Glaucoma Surgery using Goniotomy as A Potential Surgical Treatment Modality in Indonesia: A Descriptive Study and Literature Review

Introduction &amp; ObjectivesMicro-invasive glaucoma surgery with goniotomy is a recent surgical treatment modality that targetsthe trabecular outflow to maintain intraocular pressure. This study aims to describe the clinicaloutcomes of excisional goniotomy using KDB and to review the published literature regarding amodified goniotomy technique as a potential surgical treatment modality in Indonesia.&#x0D; MethodsA cross-sectional descriptive study was conducted in patients that underwent goniotomy stand-aloneor combined with cataract surgery. Main outcome parameters consist of visual acuity, intraocularpressure (IOP), number of glaucoma medications, and complications during post-operative follow-up.&#x0D; ResultsA total of 7 patients (8 eyes) were included in the study, consisting of 5 (71,4%) males and 2 (28,6%)females. The mean age of the subjects was 47.7 years. Subjects consisted of primary,pseudoexfoliative, steroid-induced, and angle-recess glaucoma. Mean pre-operative IOPmeasurements showed 20.74 mmHg with visual acuity consisting of 1 (14.3%) mild visualimpairment and 7 (85.7%) severe visual impairment. Postoperatively there was progressiveimprovement in the mean IOP to 13.81 and 11.31 mmHg on first-day and one-week follow-up,respectively. Visual improvement was observed in 2 (28.5%) with mild visual impairment, 3 (42.6%)with severe visual impairment, and 2 (28.5%) with hand movement due to complications of cornealedema following phacoemulsification. A week later, visual acuity improved to 4 (57.1%) with mildvisual impairment and 3 (42.9%) with moderate visual impairment.&#x0D; ConclusionGoniotomy is a simple surgical method that may be applied in Indonesia as a novel technique toprovide an effective intraocular pressure-lowering effect.

Childhood glaucoma profile in a Southwestern Ethiopia tertiary care center: a retrospective study

BackgroundChildhood glaucoma is a major cause of childhood blindness worldwide. The profile of childhood glaucoma has not been well characterized in sub-Saharan Africa. Thus, this study was designed to describe demographics, clinical features, managements of childhood glaucoma, and improvements in visual acuity (VA) and intraocular pressure (IOP) from baseline to final visit.MethodsThis retrospective study included glaucoma patients below 18 years old who were diagnosed between September 2019 to August 2022. Childhood glaucoma diagnosis and classification was made as per the Childhood Glaucoma Research Network Classification (CGRN).ResultsA total of 105 children (181 eyes) were diagnosed with glaucoma. The most common type of childhood glaucoma was primary congenital glaucoma (PCG) constituting (42%, n = 76 eyes, 95% confidence interval (CI), 34.7–49.5%; P = 0.037), followed by glaucoma suspect (22.1%, n = 40 eyes, 95% CI, 16.3–28.9%; P < 0.001) and juvenile open-angle glaucoma (JOAG) (15.5%, n = 28 eyes, 95% CI, 10.5–21.6%; P < 0.001). While the most common type of secondary glaucoma was steroid-induced glaucoma, followed by glaucoma following cataract surgery. Bilateral glaucoma was found in 72.4% (n = 76 children, 95% CI, 62.8–80.7%; P < 0.001) of children. In both primary and secondary glaucoma, boys were affected more than girls, in ratio of 2:1 and 2.7:1, respectively. The mean age at presentation for patients with PCG was 2.7 years. Close to 93.4% (71) of PCG eyes were managed surgically, of which majority underwent combined trabeculotomy and trabeculectomy (CTT). Most of secondary glaucoma cases were treated medically. Overall, 85.3% (111) of eyes had successful control of IOP ≤ 21 mmHg.ConclusionPCG was the most common type of childhood glaucoma. One of a well-recognized challenge in developing countries, late presentation of patients with PCG, was also observed in our study. Which highlights, the need of increasing access to eye-care service and awareness of childhood glaucoma as a major public health issue. Steroid-induced glaucoma was the most common type of secondary glaucoma; appropriate measures should be taken to prevent this preventable glaucoma.

Impact of prednisolone, dexamethasone, and fluorometholone eye drops on intraocular pressure in patients post-cataract surgery: A randomized controlled study

After cataract surgery, topical corticosteroids are prescribed for inflammation reduction, but prolonged use may lead to side effects like steroid-induced glaucoma. These steroids can elevate intraocular pressure (IOP), and if elevated IOP isn't promptly addressed, it may advance to glaucoma. Vigilant monitoring of IOP changes is crucial for early detection and intervention, forming the basis for this study.The objective of this study was to evaluate and compare the impact of post-cataract surgery administration of eye drops containing prednisolone, dexamethasone, and fluramethalone on Intra-Ocular pressure (IOP) in patients. Seventy-five patients were randomly allocated to three groups, each comprising thirty individuals. Participants were administered prednisolone, dexamethasone, and fluramethalone eye drops, respectively, with a tapered dosage over a 42-day period. The study involved documenting intraocular pressure (IOP) measurements both before and after the surgery. Subsequently, patients were monitored for a duration of three months. Among the 75 patients, approximately 5.77% (n = 4) exhibited an increase in intraocular pressure (IOP) of ≥10 mmHg from their baseline. A moderate elevation in IOP (≥5 mmHg) was observed in about 13.44% (n = 13) of the patients. Notably, a clinically significant rise in IOP, defined as an increase of ≥10 mmHg and an overall IOP of ≥20 mmHg, occurred in 4.98% (n = 4) of the patients, all of whom were in the fluramethalone group. The mean post-operative IOP differed significantly among the three treatment groups. Fluromethalone possesses a heightened propensity to induce an early and substantial increase in intraocular pressure (IOP), necessitating careful and vigilant usage with continuous monitoring.

Comparative evaluation of the effectiveness of a prostaglandin analogue and fixed-dose combination drug containing brinzolamide 1% and timolol maleate 0.5% (an experimental study)

PURPOSE. Comparative evaluation of anti-hypertensive effectiveness of tafluprost 0.0015% (Taflotan), and a fixed-combination of benzolamide 1% and timolol maleate 0.5% (Azarga) preparation in an experimental animal model with artificially induced steroidal ophthalmic hypertension.METHODS. The study experiments were performed on 30 sexually mature Chinchilla rabbits (60 eyes) with steroid-induced glaucoma modeled by ocular instillations of dexamethasone.The animals were divided into 3 groups each consisting of 10 rabbits. The first group was the controls that were divided into two subgroups; they were instilled dexamethasone 0.1% two drops per day into the right eye (the left eye remained as control) for 20 days in subgroup 1, and for 30 days in subgroup 2.The animals in group 2 received Azarga, group 3 — Taflotan. Animals of group 2 and 3 were divided into three subgroups: in subgroup 1 the animals were instilled the studied drugs for 10 days, in subgroup 2 — for 20 days, in subgroup 3 — for 30 days.RESULTS. Both drugs reduced the intraocular pressure down to the reference range, i.e. 18–25 mm Hg. Animals that received instillations of Taflotan achieved the refe rence range values after 10 days, while the animals receiving Azarga — after 20 days.CONCLUSIONS. Under the conditions of steroidal ophthalmic hypertension, instillations of both Azarga and Taflotan yield satisfactory results in terms of IOP reduction. The use of Taflotan allowed achieving the reference range values after 10 days, Azarga — after 20 days. Taking into account the ease of administration of Taflotan, it can be recommended as the most convenient and effective drug in terms of reducing intraocular pressure.

Influence of sex on chronic steroid-induced glaucoma: 24-Weeks follow-up study in rats

The objective was to evaluate ocular changes based on sex in steroid-induced glaucoma models in rats comparing healthy controls, over 24 weeks follow-up. Eighty-nine Long–Evans rats (38 males and 51 females) with steroid-induced glaucoma were analysed. Two steroid-induced glaucoma models were generated by injecting poly-co-lactic-glycolic acid microspheres loaded with dexamethasone (MMDEX model) and dexamethasone-fibronectin (MMDEXAFIBRO model) into the ocular anterior chamber. Intraocular pressure was measured by rebound tonometer Tonolab®. Neuroretinal function was analysed using dark- and light-adapted electroretinography (Roland consult® RETIanimal ERG), and structure was analysed using optical coherence tomography (OCT Spectralis, Heidelberg® Engineering) using Retina Posterior Pole, Retinal Nerve Fibre Layer and Ganglion Cell Layer protocols over 24 weeks. Males showed statistically (p < 0.05) higher intraocular pressure measurements. In both sexes and models neuroretinal thickness tended to decrease over time. In the MMDEX model, males showed higher IOP values and greatest percentage thickness loss in the Ganglion Cell Layer (p = 0.015). Females receiving MMDEXAFIBRO experienced large fluctuations in thickness, a higher percentage loss (on average) in Retina Posterior Pole (p = 0.035), Retinal Nerve Fibre Layer and Ganglion Cell Layer than aged-matched males, and the highest thickness loss rate by mmHg. Although no difference was found by sex in dark- and light-adapted electroretinography, increased amplitude in photopic negative response was found in MMDEX males and MMDEXAFIBRO females at 12 weeks. Although both glaucoma models used dexamethasone, different intraocular pressure and neuroretinal changes were observed depending on sex and other influential cofactors (fibronectin). Both sex and the induced glaucoma model influenced neuroretinal degeneration.

Bilateral Glaucoma Drainage Device (GDD) Implantation in Steroid Induced Glaucoma

Objective: This study aims to report a case of Bilateral Glaucoma Drainage Device (GDD) implantation surgery in a patient with Steroid Induced Glaucoma. Case Presentation: A 18-year-old male patient with steroid-induced glaucoma and allergic conjunctivitis. The patient also complained about red eyes and itchy in both eyes and had been using steroid eye drops for 5 years. The patient also complained about headaches and blurry vision. The patient had undergone trabeculectomy surgery 5 months ago on the left eye. The visual acuity was 6/6 on the right eye and 6/7.5 on the left eye. His intraocular pressure (IOP) on the right eye was 24 mmHg, and his left eye was 23 mmHg with conjunctival left eye bleb, flat, and fibrosis. The patient then underwent a non-valve Virna’s GDD implant surgery on the right eye. On day two post-GDD, the IOP was 4 mmHg, and the COA was shallow, so reform the COA. At the first month follow-up, the patient's right eye pressure was still in normal condition with no complications, and then the plan was for left eye Virna’s GDD implantation surgery. At the first month follow-up after left eye GDD implantation, the visual acuity was 6/9 on the right eye and 6/24 on the left eye, with IOP RE 11mmHg and LE 16mmHg, from anterior segment deep anterior chamber, no plate exposed, no leakage, and tube not attached to the corneal endothelium. The patient's intraocular pressure was still in normal condition in both eyes, and no complications was found, although the patient was still using low-dose topical steroid eye drops. Conclusion: In steroid-induced glaucoma, after trabeculectomy failure, the implantation of GDD is the most effective option in controlling high IOP and slowing down glaucoma progressivity.

Small RNA Sequencing Reveals a Distinct MicroRNA Signature between Glucocorticoid Responder and Glucocorticoid Non-Responder Primary Human Trabecular Meshwork Cells after Dexamethasone Treatment.

Glucocorticoids (GCs) are known to regulate several physiological processes and are the mainstay in the management of inflammatory eye diseases. The long-term use of GC causes raised intraocular pressure (IOP) or ocular hypertension (OHT) in about 30-50% of the susceptible individuals depending on the route of administration, and can lead to steroid-induced secondary glaucoma. The present study aims to understand the role of microRNAs (miRNAs) in differential glucocorticoid (GC) responsiveness in human trabecular meshwork (HTM) cells using small RNA sequencing. The human organ-cultured anterior segment (HOCAS) model was used to identify whether donor eyes were from GC-responders (GC-R; n = 4) or GC-non-responders (GC-NR; n = 4) following treatment with either 100 nM dexamethasone (DEX) or ethanol (ETH) for 7 days. The total RNA was extracted from cultured HTM cells with known GC responsiveness, and the differentially expressed miRNAs (DEMIRs) were compared among the following five groups: Group #1: ETH vs. DEX-treated GC-R; #2: ETH vs. DEX-treated GC-NR; #3: overlapping DEGs between Group #1 and #2; #4: Unique DEMIRs of GC-R; #5: Unique DEMIRs of GC-NR; and validated by RT-qPCR. There were 13 and 21 DEMIRs identified in Group #1 and Group #2, respectively. Seven miRNAs were common miRNAs dysregulated in both GC-R and GC-NR (Group #3). This analysis allowed the identification of DEMIRs that were unique to GC-R (6 miRNAs) and GC-NR (14 miRNAs) HTM cells, respectively. Ingenuity Pathway Analysis identified enriched pathways and biological processes associated with differential GC responsiveness in HTM cells. This is the first study to reveal a unique miRNA signature between GC-R and GC-NR HTM cells, which raises the possibility of developing new molecular targets for the management of steroid-OHT/glaucoma.

Evaluation of New and Preexisting Epiretinal Membranes Following Glaucoma Filtration Surgery.

Secondary epiretinal membranes (ERMs) can develop from various causes, including those associated with glaucoma treatments such as trabeculectomy (TLE) and EX-PRESS (EXP) insertion surgery. This study aimed to investigate the occurrence of new ERMs and changes in preexisting ERMs following TLE or EXP insertion. Between April 2018 and March 2019, 102and 74 eyes that underwent primary and standalone TLE and EXP insertion, respectively, were evaluated. Of these, 48 eyes were included in the TLE groupand 32 eyes were included in the EXP group. Optical coherence tomography (OCT) was used to assess preoperative and postoperative ERMs. In the TLE group, postoperative ERMs were observed in one (case 1) (3%) out of 34 eyes without preexisting ERMs and in one (case 2) (7%) out of 14 eyes with preexisting ERMs, showing an increase in ERM stage. In the EXP group, postoperative ERMs were observed in one (case 3) (5%) out of 22 eyes without preexisting ERMs and in one (case 4) (10%) out of 10 eyes with preexisting ERMs, showing a decrease in the ERM stage. Case 1 was a 58-year-old man with primary open-angle glaucoma (POAG) in the left eye who underwent TLE. Although no preoperative ERMs were observed, postoperative ERM was noted at the three-month follow-up. Case 2 was a 49-year-old man with POAG in the right eye who underwentTLE. Although ERM was observed preoperatively, ERM progressed at six months postoperatively. Case 3 was a 59-year-old woman with POAG in the right eye who underwent EXP insertion.No preoperative ERMs were observed, but an ERM was noted at the 15-month follow-up. Case 4 was a 72-year-old woman with steroid-induced glaucoma in the right eye who underwent EXP insertion surgery. A preoperative ERM was present, and the foveal pit was absent; however, the foveal pit was observed at the 12-month follow-up. Despite the low incidence of ERMs, filtration surgery may be associated with ERM development and the progression or regression of preexisting ERMs.

Prevalence of glaucoma types, clinical profile and disease severity at presentation: Tertiary Institute based cross-sectional study from South India.

To describe the clinical profile and relative prevalence of subtypes of glaucoma presenting to a tertiary care center in India. This cross-sectional hospital-based study included 6,120 new patients (>16 years) presenting between January 2016 and December 2017. The data were collected using an electronic medical record system. A total of 11,016 eyes of 6,120 new patients were diagnosed with glaucoma. Sixty-one percent were male and 79% had a bilateral affliction. Primary glaucoma was present in 4,352 (71.1%) and secondary glaucoma in 1,063 (17.4%) subjects. Glaucoma was primary open-angle (POAG) in 4,015 (36.4%) eyes and primary angle closure disease (PACD) in 3,806 (34.5%) eyes. Commonest among secondary glaucoma was post-cataract surgery glaucoma (3.1%), neovascular glaucoma (2.4%), pseudoexfoliation glaucoma (PXG) (2.1%), and steroid-induced glaucoma (SIG) (1.4%). Patients with primary glaucoma were older than secondary (56.6 ± 0.2 vs 54.1 ± 0.4; P < 0.0001). Mean IOP was higher in secondary glaucoma compared to primary (26.9 ± 0.3 vs 18.9 ± 0.1; P < 0.0001). Secondary glaucoma had greater mean CDR compared to primary glaucoma (0.77 ± 0.007 vs 0.70 ± 0.003; P < 0.0001). The prevalence of blindness (visual acuity <20/200) was 16.2% of eyes. Mean deviation (MD) 20db or worse was noted in 39.5% of eyes at presentation including 47.8% of PACG, 37.3% of POAG, 51% of JOAG, 58% of PXG, and 45% of SIG, suggesting disease severity. At the presentation to a tertiary care center, 40% of all eyes with glaucoma had advanced disease with MD worse than - 20D. PACG and JOAG had the worse disease among primary; among secondary, PXG and SIG had the worse disease at presentation.

Bilateral Steroid Induced Glaucoma In A 10-year-old Boy

Introduction: Topical steroids are used in the treatment of various ocular disorders. However, it can cause numerous side effects. Steroid-induced glaucoma is the most severe complication of the unmonitored use of steroids. It is diagnosed by visual field defects, increased intraocular pressure (IOP), and glaucomatous optic neuropathy (GON) due to prolonged usage of steroids. Case Presentation: a 10-year-old boy presented to the outpatient clinic in Undaan Eye Hospital complaining of headache, re dness and itchiness in both eyes. He started using dexamethasone 0.1% eye drops without a physician's supervision for the last 2 years. Steroid-induced glaucoma was diagnosed in both eyes. Topical and oral glaucoma medications were given. Both eyes IOP were still elevated in the following months. Trabeculectomy in both eyes was performed due to medically uncontrolled glaucoma. Furthermore, both eyes IOP were getting normal without any topical and oral glaucoma medications. Conclusion: Unmonitored steroid usage must be avoided. This case suggests general practitioners and health care providers in the front line be aware of the usage of topical steroids. By increasing awareness concerning steroid-induced glaucoma, a patient's visual acuity can be saved, and irreversible blindness can be prevented, especially in children.

Toxic retrobulbar neuritis due to recurrent nonsteroidal antiinflammatory drug-exacerbated respiratory disease-based chronic sinusitis in the left sphenoid sinus: a case report

BackgroundAbrupt visual impairment constitutes a medical urgency, necessitating an interdisciplinary diagnostic and therapeutic approach owing to the broad spectrum of potential etiologies, thereby engaging numerous medical specialties.Case presentationA 21-year-old Mixed White and Asian female patient, with medical history of nonsteroidal antiinflammatory drug-exacerbated respiratory disease necessitating previous sinus surgery, reported sudden monocular vision loss. Unremarkable ophthalmological examination of the fellow eye and hematological parameters, save for a slight elevation in lymphocytes and eosinophils, were observed. Imaging studies indicated recurrence of bilateral chronic rhinosinusitis with nasal polyps and a mucocele in the left sphenoid sinus, accompanied by bony structural deficits. Emergency revision sinus surgery, guided by navigation, was promptly performed. The patient received treatment with methylprednisolone, ceftriaxone, cyanocobalamin, pyridoxine, thiamine, and acetylsalicylic acid. During the hospital stay, she developed steroid-induced glaucoma, which was subsequently managed successfully. Negative microbiological swabs, along with pathohistological evidence of increased tissue eosinophilia and the patient’s clinical history, led to the diagnosis of toxic retrobulbar neuritis secondary to recurrent nonsteroidal antiinflammatory drug-exacerbated respiratory disease-associated chronic rhinosinusitis of the left sphenoid sinus.ConclusionsIn cases of acute unilateral vision loss, optic neuritis is a highly probable differential diagnosis and may be induced by pathologies of the paranasal sinuses. Nonsteroidal antiinflammatory drug-exacerbated respiratory disease, a subtype of chronic rhinosinusitis, is associated with type 2 inflammation, which is increasingly recognized for its role in the pathogenesis of bronchial asthma, eosinophilic esophagitis, and atopic eczema. Clinicians should consider chronic rhinosinusitis as a potential differential diagnosis in unilateral visual loss and be cognizant of the rising significance of type 2 inflammations, which are relevant to a variety of diseases.