Steroid-induced Glaucoma Research Articles

Steroid-induced glaucoma after laser in situ keratomileusis associated with interface fluid

PurposeTo report the ocular manifestations and clinical course of eyes developing interface fluid after laser in situ keratomileusis (LASIK) surgery from a steroid-induced rise in intraocular pressure. DesignRetrospective, noncomparative interventional case series. Participants/interventionWe examined six eyes of four patients who had diffuse lamellar keratitis develop after uneventful myopic LASIK surgery and were treated with topical corticosteroids. Principal outcome measureSlit-lamp findings, intraocular pressure measurements, and visual field loss. ResultsAll eyes had a pocket of fluid develop in the lamellar interface between the flap and the stromal bed associated with a corticosteroid-induced rise in intraocular pressure. However, because of the interface fluid, intraocular pressure was normal or low by central corneal Goldmann applanation tonometry in all eyes. The elevated intraocular pressure was diagnosed by peripheral measurement in several cases after months of elevated pressure. All six eyes had visual field defects develop. Three eyes of two patients had severe glaucomatous optic neuropathy and decreased visual acuity develop as a result of undiagnosed steroid-induced elevated intraocular pressure. ConclusionsA steroid-induced rise in intraocular pressure after LASIK can cause transudation of aqueous fluid across the endothelium that collects in the flap interface. The interface fluid leads to inaccurately low central applanation tonometry measurements that obscure the diagnosis of steroid-induced glaucoma. Serious visual loss may result.

Progression to end-stage glaucoma after laser in situ keratomileusis

We describe 2 patients, one a glaucoma suspect because of family history and the other with juvenile glaucoma. Both patients developed complications after laser in situ keratomileusis that required frequent topical steroids, leading to steroid-induced glaucoma. In both cases, corneal edema from the acute rise in intraocular pressure (IOP) caused inaccurate IOP measurement by standard methods. The inability to recognize glaucoma early may have resulted in significant irreversible vision loss.

Post-transcriptional modification of the gene genetically linked to juvenile open-angle glaucoma; novel transcripts in human ocular tissues

Mutation in the myocilin gene is associated with 4% (familial form) of glaucoma cases. The underlying mechanism in non-familial cases remains unclear. Myocilin is shown here to undergo a post-transcriptional modification event, giving rise to deletion forms. Data presented show the expression profile of the shorter transcripts occurs in a tissue-specific and donor-specific manner, and the possibility is raised that their expression is disease-associated. Furthermore, demonstration of their upregulation by dexamethasone provide support for a possible role in steroid-induced glaucoma, a model for the disease process of glaucoma.

Expression of cyclooxygenase-1 and -2 in normal and glaucomatous human eyes.

Primary open-angle glaucoma (POAG) is the predominant form of chronic glaucoma, but the underlying pathologic mechanisms are largely unknown. Because prostaglandins (PGs) have been introduced into POAG treatment with remarkable success, this study was undertaken to investigate whether a change in the expression of the PG-synthesizing enzymes cyclooxygenase (COX)-1 and -2 might be involved in the pathogenesis of POAG. Expression of COX-1 and -2 was assessed by confocal laser microscopy, immunohistochemistry, Western blot analysis, and real-time RT-PCR in human eyes with different forms of glaucoma (primary open-angle, angle-closure, congenital juvenile, and steroid-induced), as well as in age-matched control eyes. Additionally, PGE2 was measured in aqueous humor by means of an enzyme-linked immunoassay as a product of COX activity. In normal eyes, ocular COX-1 and -2 expression were largely confined to the nonpigmented secretory epithelium of the ciliary body. By immunohistochemistry and real-time RT-PCR, COX-2 expression was completely lost in the nonpigmented secretory epithelium of the ciliary body of eyes with end-stage POAG, whereas COX-1 expression was unchanged. By immunohistochemistry, in the ciliary bodies of eyes in five patients with diagnosis of early POAG, eyes in two had complete loss of COX-2 expression and in three showed only a few remaining scattered COX-2-expressing cells. COX-2 expression in the ciliary body was also lost in patients with steroid-induced glaucoma and was reduced in patients receiving topical steroid treatment. Eyes of patients with either congenital juvenile or angle-closure glaucoma showed COX-2 expression indistinguishable from control eyes. Aqueous humor of eyes with POAG contained significantly less PGE2 than control eyes. Both cyclooxygenase isoforms are constitutively expressed in the normal human eye. Specific loss of COX-2 expression in the nonpigmented secretory epithelium of the ciliary body appears to be linked to the occurrence of POAG and steroid-induced glaucoma.

Ocular complications of paediatric patients with nephrotic syndrome.

To investigate ocular complications arising from nephrotic syndrome and/or its treatments in children. A cross-sectional study was conducted in a teaching hospital. A total of 31 paediatric patients with nephrotic syndrome were studied. Comprehensive ophthalmic assessments on best-corrected visual acuity, intraocular pressure, slit-lamp and fundus examination were taken. Information regarding histological diagnosis of nephrotic syndrome and its treatment regimen in each patient was reviewed and analysed. Bilateral posterior subcapsular cataracts were detected in three of 29 patients (10.3%) who received steroid therapy. Two had normal vision while one had visual acuity reduced to 6/15 in both eyes. The age of onset of the nephrotic syndrome in these three patients was 2 years, which was significantly younger than those without cataract (5.4 +/- 3.2 years, P < 0.001). Three patients (9.7%) had isolated asymptomatic fundal findings of tortuous and dilated retinal vessels. Hypertensive retinopathy was found in one patient (3.2%). No steroid-induced glaucoma, uveitis, ocular infection, or other eye complications related to the use of steroids or other immunosuppressive agents were noted. Children who have nephrotic syndrome often require prolonged, intermittent high dose of systemic corticosteroid therapy. Paediatricians should be aware of the potential risk of developing steroid-related complications, especially posterior subcapsular cataract. It appears to have a higher risk when steroid therapy is used in very young patients. Early detection would help to prevent amblyopia development, particularly in the group of immature eyes.

External trabeculotomy for the treatment of steroid-induced glaucoma.

To investigate the effect of external trabeculotomy on eyes with steroid-induced glaucoma. We retrospectively analyzed the surgical results of 14 eyes of seven patients that underwent trabeculotomy for the first surgical procedure. All patients had the history of receiving topical or systemic corticosteroids before the rise of intraocular pressure had been noted. After an average follow-up of 60.6 +/- 33.5 months, in all of the 14 eyes, intraocular pressure was well controlled below or equal to 21 mm Hg at the final examinations. Surgical results of external trabeculotomy remain effective for a long time. It has been shown that the trabeculotomy can be a useful and effective surgical treatment of patients with steroid-induced glaucoma.

Tubulointerstitial nephritis and uveitis with bilateral multifocal choroiditis

PURPOSE: To report a case of bilateral multifocal choroiditis secondary to tubulointerstitial nephritis and uveitis. METHODS: Case report. A 16-year-old women with an 11-month history of tubulointerstitial nephritis and uveitis and bilateral anterior uveitis developed bilateral multifocal choroiditis. After initial unsuccessful treatment with topical steroids, treatment was augmented by a 2-week course of systemic prednisone. RESULTS: Intensive steroid treatment resulted in steroid-induced glaucoma, which required bilateral trabeculectomies, but the uveitis became inactive. Two years after uveitis onset, bilateral intraocular pressure was normal, there were occasional ( 1 2 +) anterior chamber cells, and inactive depigmented chorioretinal lesions on topical steroid drops. See also pp. 764–768, 798–799. CONCLUSIONS: Tubulointerstitial nephritis and uveitis usually involves only the anterior uvea, although a few cases of posterior uveitis have been described. This article reports a case of multifocal choroiditis associated with tubulointerstitial nephritis and uveitis. It is important for ophthalmologists to be aware of possible posterior uveal involvement in tubulointerstitial nephritis and uveitis so they can choose the most appropriate immunosuppressive therapy for the uveitis.

Vernal keratoconjunctivitis revisited: A case series of 195 patients with long-term followup

Objective: This study aimed at revisiting vernal keratoconjunctivitis (VKC) on the basis of anamnestic, clinical, immunologic, histopathologic, and followup data of 195 patients. Design Retrospective noncomparative case series. Participants: One hundred and ninety-five patients with VKC. Methods Clinical evaluation and outcome in 151 of 195 patients with a median followup of 47 months. Evaluation was by telephone survey in 69 patients. Main outcome measures (1) Demographic, clinical, and immunologic features of VKC and their influence on the course of the disease; (2) conjunctival and corneal complications and efficacy of treatment observed during the followup period. Results VKC is a chronic disease. More than 60% of patients had repeated recurrences all year round. Males had an earlier presentation of symptoms than females and the male/female ratio decreased with age. Major (greater than 80%) and minor (up to 80%) diagnostic criteria were defined for clinical signs and symptoms of the disease. Negative skin test or radioallergosorbent test was present in approximately 50% of patients, whereas eosinophil infiltration was a constant histopathologic finding. A marked conjunctival sensitivity to nonspecific stimuli was noted in more than one third of patients. In 6% of cases, a reduction of visual acuity resulted from corneal scarring, and in 2% of patients, steroid-induced glaucoma was observed. The large size of giant papillae indicates poor prognosis for the persistence of the disease and its evolution into a chronic, perennial condition. Conclusions: VKC is a chronic eosinophilic disease of the ocular surface involving IgE, non IgE-mediated mechanisms, and age-sex–related influences. Although the disease has a good prognosis, severe visual impairments may result from long-standing inflammation.

Superficial Punctate Keratitis of Thygeson

To report the extended clinical course of a case of superficial punctate keratitis of Thygeson. A 59-year-old woman with a 40-year history of superficial punctate keratitis of Thygeson is presented, providing a forum to discuss the chronicity of the disease, its treatment, and the potential complications. Our patient has been treated over the years with mild topical corticosteroids, usually with favorable results. Given the chronicity of superficial punctate keratitis of Thygeson, long-term treatment with topical corticosteroids carries the possible side effects of iatrogenic cataract formation and steroid-induced glaucoma, neither of which was seen in our patient. Superficial punctate keratitis of Thygeson is usually a benign, self-limited disease with exacerbations and remissions. Ophthalmologists must exercise care when using long-term corticosteroid treatment in this condition.

The epidemiology of pediatric glaucoma: The Toronto experience

Background: This study was conceived to provide an insight into the spectrum of glaucoma in the pediatric population. We also set out to compare the success of disease control and the prognosis for vision within the different diagnostic subgroups. This is the largest single population of children with glaucoma that has been so described and compared. Methods: The charts of children who were first seen between birth and age 16 years and who attended the Hospital for Sick Children with any form of glaucoma between January 1974 and January 1995 were reviewed and entered into the study. Results: Data are presented for 306 children. Congenital glaucoma was the most common subtype, accounting for 38%. Patients with congenital glaucoma were young, had surgery, and had more operations than any other group except those with aniridia. Goniotomy offered a cure in 47.8% of the patients. A bimodal distribution reflected their visual performance. Patients with aphakic glaucoma, the next most prevalent group (20%), presented at an older age (4.5 years). Surgical intervention was performed in 50% of these children. Nearly all patients with Sturge-Weber syndrome (80%) had surgery. The following glaucoma groups were associated with a poor visual outcome: aniridia, anterior segment developmental anomalies involving the cornea, uveitis with glaucoma other than steroid induced, retinopathy of prematurity, and persistent hyperplastic primary vitreous. Steroid-induced glaucoma and anterior segment dysgenesis, excluding Peters anomaly, had uniformly good outcomes. Conclusion: The ability to control glaucoma in childhood and visual prognosis is highly variable. Particular diagnostic categories do consistently well and some do poorly. (J AAPOS 1999;3:308-15)

Clinical Results and Complications of Refractive Surgery

To evaluate the efficacy of photorefractive keratectomy (PRK) with a scanning type excimer laser MEL-60 (AESCLUP-MEDITEC, Co). We performed PRK on 102 eyes of 62 myopic patients whose refraction ranged from-3.00 to -12.50 D (mean, -6.47 D) and examined the clinical results of postoperative refraction and complications. At 12, 18, and 24 months after the operation, the mean refraction was -1.57 +/- 1.25D, -1.63 +/- 1.51 D and -1.73 +/- 1.47 D. At 12 months after the operation, 36 eyes (46.2%) were within +/- 0.5 D of intended correction, 61 eyes (78.3%) within +/- 1.0 D, and 76 eyes (97.4%) within +/- 2.0 D. Twenty-four months after the operation, 12 eyes (37.5%) were within +/- 0.5 D, 18 eyes (56.3%) within +/- 1.0 D and 29 eyes (90.6%) within +/- 2.0 D. The complications were as follows: keratitis filamentosa was observed in 10 eyes (10.5%), decrease of contrast sensitivity in 7 eyes (7.4%), subepithelial corneal haze in 4 eyes (1.2%), steroid-induced glaucoma was 2 eyes (2.1%), increase of astigmatism in 2 eyes (2.1%), decrease of best corrected visual acuity in 2 eyes (2.1%), and corneal ulcer in 1 eyes (1.1%). PRK with a scanning type excimer laser MEL-60 was effective to reduce refractive error in low and mild myopia, but there were some complications, so that a long, careful follow-up seems necessary.

Steroid-Induced Glaucoma in a Young Woman

Steroid-Induced Glaucoma in a Young Woman

The Effect of Dexamethasone on Integrin and Laminin Expression in Cultured Human Trabecular Meshwork Cells

Glucocorticoid treatment in vivo can produce a glaucoma similar in many ways to POAG. Treatment of trabecular meshwork cells in culture with dexamethasone allows the study of biochemical aspects of this disease process. The effects of dexamethasone on the expression of integrins and laminin in both normal and glaucomatous cultured human trabecular meshwork cells were evaluated. Human trabecular meshwork cell lines were cultured for 18 days in the presence or absence of 10−7mdexamethasone. Radioimmunoprecipitation was used to determine the relative expression of five αintegrin subunits. Laminin expression was evaluated with Western blots. Laminin was increased in all cell lines following dexamethasone treatment. α2, α5 and αV integrin chains showed consistent dexamethasone-induced changes in expression, while α3 and α4 subunits did not. There were no differences in the expression patterns for any of these integrin subunits between normal and glaucomatous cell lines. Increased laminin deposition as seen in this study with dexamethasone treatment may be partially responsible for the decreased outflow facility seen in both steroid-induced glaucoma and in POAG.

Combined myopia-astigmatism correction. A comparison with pure myopia correction

Myopic PRK up to 6 D is an approved and safe procedure. The efficacy and safety of combined treatment of myopia and astigmatism in compound myopic astigmatism (PARK) have not yet been demonstrated. In a prospective study in 342 eyes the results of myopic PRK were compared to those of correction of compound myopic astigmatism (PARK). Regarding spherical refraction achieved there was no significant difference between groups. Best corrected visual acuity only improved in the group with high astigmatism; this group also showed the least number of Central Islands. Permanent haze and steroid-induced glaucoma or cataract were not observed after treatment up to 6 D. Average astigmatism of 2.24 D was be reduced to 0.53 D 1 year post-operatively. Correction of astigmatism resulted in undercorrection of approximately 30%. Our experience with the keracor shows PRK up to 6 D with or without additional correction of astigmatism (PARK) to be comparatively safe in terms of regression and complications and equally accurate in reaching spherical target refraction.

Ultrastructural changes in the trabecular meshwork of juvenile glaucoma.

Trabeculectomy specimens from 11 patients with juvenile glaucoma were studied by electron microscopy and quantitatively evaluated. In all cases, large amounts of extracellular material arranged in a fingerprint-like pattern, resembling basement-membrane-like material (FBM) was found, similar to that described in steroid-induced glaucoma. This material was found mainly within the inner cribriform and outer corneoscleral regions of the trabecular meshwork, and caused the cribriform layer to be greatly thickened. FBM was also intimately associated with trabecular cells, which frequently appeared activated. In 3 cases, there was also an increase in fine fibrillar material which resembled that found in eyes with steroid-induced glaucoma. The amount of sheath-derived plaque material, which is increased in primary open angle glaucoma, was greatly increased in the subendothelial layer adjacent to Schlemm's canal.

Corticosteroid Treatment and Trabecular Meshwork Proteases in Cell and Organ Culture Supernatants

Steroid-induced glaucoma is believed to result from increased aqueous outflow resistance and evidence suggests that this is the result of an excess accumulation of extracellular matrix components. This accumulation could result from an imbalance in the natural turnover of these components.We have investigated the effect of corticosteroid treatment of trabecular meshwork (TM) organ and cell cultures on the extracellular activities of the matrix metalloproteinases and plasminogen activators. We find that corticosteroid treatment results in decreased extracellular activity of stromelysin and tissue plasminogen activator in trabecular meshwork cell culture, and decreased 92 kDa collagenase IV, stromelysin, and tissue plasminogen activator in trabecular meshwork organ culture. These data suggest that decreased levels of proteolytic activities could account, in part, for the accumulation of some extracellular matrix components and be a contributing mechanism in steroid-induced glaucoma.

Pseudoexfoliation-syndrome: Intraocular manifestation of a systemic disorder?

Transforming growth factor-β2 (TGF-β2) is elevated in the aqueous humor of patients with primary open-angle glaucoma (POAG), and high levels of TGF-β2 are thought to contribute to the pathogenesis of POAG. Most TGF-β2 in the eye is present in a latent, inactive form and the mechanisms of its in vivo activation are unclear. Since thrombospondin-1 (TSP-1) is one of the most potent in vivo activating molecules of TGF-βs, we investigated the localization and expression of TSP-1 in the aqueous humor outflow pathways. TSP-1 immunohistochemistry was performed in the eyes of human donors (8 normal and 17 with glaucoma). In addition, the eyes of Tsp-1−/−-deficient mice and normal Tsp-1+/+ mice were investigated. TSP-1 mRNA expression was assessed by reverse transcription-polymerase chain reaction and Northern blotting of RNA from fresh trabecular meshwork (TM), and human and mouse TM cells in vitro. In addition, Northern and Western blot analyses of TM cells after incubation with TGF-β and dexamethasone were performed. In most of the eyes, TSP-1 immunolabeling was predominately observed in extracellular areas of the juxtacanalicular (cribriform) part of the TM. Some focal staining was observed in the corneoscleral and uveal parts of the TM. In the eyes of six glaucoma patients (including one with steroid-induced glaucoma), TSP-1 immunoreactivity was considerably more intense and all regions of the TM were positively labeled. In double labeling experiments, staining for TSP-1 did not overlap with that of fibronectin or type VI collagen. mRNA for TSP-1 was detected in both fresh and cultured TM cells. Incubation of TM cells with TGF-β1 and dexamethasone caused a marked increase in TSP-1 expression. TSP-1 in the TM might act as a potent local endogenous activator of TGF-βs in the aqueous humor and mediate any local effects of TGF-β and/or dexamethasone on the outflow of aqueous humor.

Corticosteroid treatment for inflammatory bowel disease in pediatric patients increases intraocular pressure

Intraocular pressure (IOP) was measured in 54 pediatric patients (aged 7–21 years) with inflammatory bowel disease (IBD) who were treated with oral prednisone for 1–104 months. The difference in mean IOP between the treated patients (mean ± SD, 15.62 ± 4.11 mm Hg) and 55 age-matched controls (13.83 ± 2.42 mm Hg) was statistically significant (P = 0.007). The IBD patients were classified as group I, IOP ≤19 mm Hg in both eyes, and group II, IOP ≥ 20 mm Hg in either eye. Twelve of the 54 patients (22.2%) and none of the controls had IOP ≥ 20 mm Hg (P < 0.001). Seventeen of the 54 patients (31.5%) were characterized as “steroid responders” (IOP of ≥ 20 mm Hg, change in IOP of ≥ 6 mm Hg between visits, or difference in IOP of ≥ 6 mm Hg between the two eyes). When the dose of prednisone was reduced to 0–10 mg/day 30 days or more before measurement, 9 steroid responders showed a decrease in IOP to within 2 SD of the mean control IOP; 7 of the 9 showed a decrease in IOP of ≥ 6 mm Hg. These observations indicate that while prednisone is a causative factor in increasing the IOP, susceptibility to average doses of prednisone is highly variable, and patients need to be monitored on an individual basis. Because IBD is a chronic disorder that requires prolonged corticosteroid treatment, these children are at risk of developing steroid-induced glaucoma. Careful ophthalmologic monitoring of pediatric IBD patients, as well as of other pediatric patients who receive corticosteroid therapy, is recommended.

Foreword

Glucocorticoids are a class of anti-inflammatory drugs commonly used to treat various ocular and systemic conditions. Although the role of glucocorticoids in the treatment of numerous serious inflammatory diseases is pivotal, their prolonged use may increase intraocular pressure resulting in steroid-induced glaucoma. We provide a detailed update on steroid-induced glaucoma as a preventable cause of blindness in the adult and pediatric population and describe its epidemiology, social impact, and risk factors. Furthermore, we explore the propensity of different steroids to increase the intraocular pressure, the role of different routes of steroid administration, dosage and duration of treatment, as well as the clinical features, genetics, and management of steroid-induced glaucoma.

Determination of zinc and zinc-containing compound in rabbit aqueous humour by high performance aqueous gel permeation chromatography-atomic absorption spectrophotometry.

Zinc content in rabbit aqueous humour was first determined by atomic absorption spectrophotometry. In the normal rabbit, the content ranged from 0.04 to 0.06 mg/l, but in the rabbit with steroid-induced glaucoma ( SIG ), it increased and ranged from 0.1 to 0.50 mg/l. Further, in the steroid ( cortisone, 0.3 mg ) injected rabbit ( SIR ), the zinc content ranged from 0.06 to 0.09 mg/l. The precision of the measurement was within 0.01 mg/l. The minimal detection limit was 0.03 mg/l. A zinc-containing compound ( Mw, about 6000 ) was detected in the aqueous humour with the combined system of a high performance aqueous gel permeation chromatograph and an atomic absorption spectrophotometer. This zinc compound was always induced in the aqueous humour when the total zinc content exceeded 0.1 mg/l, i.e., in the case of the rabbit with SIG. On the other hand, the zinc compound could be occasionally induced in the fluid of SIR but not in the normal one. The analytical time required for the detection of the zinc compound was within 40 min. The usefulness of the analysis of zinc and the zinc-containing compound in the aqueous humour is suggested for the clinical diagnosis of SIG, one of the ophthalmic diseases.