Intraocular pressure-raising potential of 1.0% rimexolone in patients responding to corticosteroids

OBJECTIVE: To compare the intraocular pressure (IOP) elevating potential of 1.0% rimexolone and 0.1% fluorometholone alcohol ophthalmic suspensions in patients known to have responded to corticosteroids. DESIGN: In a double-masked, randomized, single-eye, crossover protocol, corticosteroid responsiveness initially was verified in 40 asymptomatic known steroid responders by challenge with either 0.1% dexamethasone sodium phosphate or 1.0% prednisolone acetate for up to 6 weeks. After a 1-month medication washout, subjects randomly received either rimexolone or fluorometholone for 6 weeks. Medications were again discontinued for 1 month, and subjects then received the alternate drug for 6 weeks. RESULTS: There was no significant difference between rimexolone and fluorometholone in the number of subjects demonstrating a 10-mm Hg increase in IOP or in the mean number of weeks required to achieve a 10-mm Hg response. Responses occurred in significantly more subjects receiving dexamethasone sodium phosphate (P = .001) or prednisolone acetate (P < .001) and in a significantly shorter interval than in subjects receiving rimexolone. CONCLUSIONS: Rimexolone has a low IOP-elevating potential, comparable to that of fluorometholone and less than that of dexamethasone sodium phosphate and prednisolone acetate.     

Effect of topical anti-inflammatory treatment on the outcome of laser trabeculoplasty. The Fluorometholone-Laser Trabeculoplasty Study Group

PURPOSE: We investigated the effect of anti-inflammatory treatment on the outcome of argon laser trabeculoplasty. METHODS: In this multicenter, double-masked, randomized, placebo-controlled, parallel comparison study, 140 chronic open-angle glaucoma patients received either 0.25% fluorometholone or vehicle four times a day unilaterally, beginning 24 hours before and continuing one week after argon laser trabeculoplasty. The laser surgeon placed 50 to 60 burns over the inferior 180 degrees of the trabecular meshwork. The patients were followed up frequently for five weeks after the procedure. RESULTS: Following argon laser trabeculoplasty, signs of anterior chamber inflammation were significantly lower in the fluorometholone group. However, there was no significant difference between the fluorometholone and the vehicle groups in the incidence of increased intraocular pressure in the immediate post-argon laser trabeculoplasty period. Intraocular pressure decreased significantly in both groups from day 1 throughout the follow-up period. A significant between-group difference in intraocular pressure decrease was found only at week 5 (7.83 +/- 6.27 [S.D.] mm Hg for the fluorometholone group vs 6.63 +/- 5.79 mm Hg for the vehicle group, P = .046). No drug-related clinically significant adverse events were observed. CONCLUSIONS: Use of fluorometholone is effective in attenuating inflammation and has no clinically significant impact on the outcome of argon laser trabeculoplasty or on the incidence of intraocular pressure spikes during the immediate post-argon laser trabeculoplasty period.     

Corticosteroid-induced cutaneous atrophy and telangiectasia. Experimental production associated with weight loss in rats

A bioassay for the evaluation of certain adverse effects of various corticosteroids was performed. Twenty-eight daily topical applications of corticosteroids to young rats produced reduction in body-weight gain, atrophy of the skin as determined by double skin-fold thickness micrometer measurement, and mild to severe telangiectasia. This animal model demonstrates corticosteroid-induced skin atrophy and telangiectasia and the correlation of the degree of atrophy and telangiectasia to body-weight change. Nine corticosteroids were evaluated by this method and are listed in terms of increasing severity of side-effects as follows: 1.0% hydrocortisone cream, 0.1% betamethasone valerate cream, 0.025% betamethasone benzoate cream, 0.05% flurandrenolide cream, 0.05% fluocinonide cream, 0.1% dexamethasone cream, and 0.03% flumethasone pivalate cream. Triamcinolone acetonide cream, 0.5%, and 0.2% fluocinolone acetonide cream resulted in death of the animals prior to completion of 28 days of topical application.     

Preventive effects of diclofenac ophthalmic solution on post-cataract-surgical cystoid macular edema

Using eyes undergoing phacoemulsification followed by implantation of a foldable acrylic intraocular lens (IOL) designed for small-incision cataract surgery, a multi-center study was performed to compare a non-steroidal ophthalmic solution (0.1% diclofenac) to a steroidal ophthalmic solution (0.1% fluorometholone) in preventing cystoid macular edema (CME) and inducing disruption of the blood-aqueous barrier determined by laser flare cellmetry. The incidence of CME, noted in 3 out of 53 eyes (5.7%) receiving diclofenac and in 29 out of 53 eyes (54.7%) receiving fluorometholone, was significantly lower in the diclofenac group. The flare in the anterior chamber was also significantly lower in the diclofenac group; when compared between eyes with and without CME, the amount of flare was significantly higher in the former group. These findings suggest that diclofenac effectively prevents CME following cataract surgery and that CME is closely related to the breakdown of the blood-aqueous barrier.     

Betamethasone-induced ocular hypertension in rabbits

The effect of subconjunctivally injected betamethasone on intraocular pressure (IOP) was studied in 85 albino New Zealand rabbits. IOP was measured with a Mentor Model 30 classic pneumatonograph that was manometrically calibrated to the rabbit eye. Ocular hypertension was induced by weekly subconjunctival injections of a betamethasone suspension into the left eye. In one experiment, 70 rabbits were given betamethasone for 4 weeks, while a second group of 10 rabbits received betamethasone for 11 weeks. The short-term effects of subconjunctival injections of betamethasone on IOP were also recorded in a third group of 5 rabbits. Weekly injections over 4 weeks resulted in an increase in IOP in the treated eye, which was prolonged to 11 weeks by repeated weekly injections. A sustained increase in IOP was observed in the treated eye for a period of 7 weeks. During the early hours after betamethasone injection, a transient decrease in IOP was registered in both eyes. The results show that weekly subconjunctival injections of betamethasone cause a predictable increase in IOP in the treated eye which may be suitable for testing the short- and long-term effects of antiglaucoma drugs. Evidence suggesting that endogenous glucocorticoids may play a role in the development of ocular hypertension in humans strengthens the potential value of this glaucoma model.     

Effect of systemic pretreatment with betamethasone on the bacterial flora, inflammatory response, and polyp formation in experimentally infected rabbit maxillary sinus mucosa

To investigate possible effects of corticosteroids on polyp formation and local bacterial colonization, pneumococcal sinusitis was experimentally induced in rabbits pretreated with betamethasone or saline. After 7 days, macroscopic polyps were counted post-mortem and on histologic slides after serial sectioning. Histologic sections were also examined with light microscopy. Macroscopic polyps were significantly fewer in animals given betamethasone, while there was no difference regarding the number of microscopic polyps. Ingrowth of pathogenic microorganisms was found in five of eight rabbits given placebo but in none of the animals treated with corticosteroids (P < 0.05). The reduced number of pathogenic strains in these animals may be explained by a better-preserved local host defense. The lower number of macroscopic polyps in the same animals could be because of a delayed mucosal repair and subsequent polyp formation.     

Minimum interval from fetal betamethasone treatment to postnatal lung responses in preterm lambs

OBJECTIVE: We hypothesized that fetal betamethasone exposure for < 24 hours would improve postnatal lung function in preterm lambs. STUDY DESIGN: Singleton fetal sheep were randomized to receive by ultrasonographically guided fetal injections of 0.5 mg/kg betamethasone or saline solution either 8 or 15 hours before preterm delivery and postnatal assessment of lung function. RESULTS: After the 15-hour fetal treatment-to-delivery interval, betamethasone-treated lambs had twofold improvement in compliance and lung volumes, a fourfold to fivefold decrease in edema index, and higher blood pressures than saline solution-treated lambs. Postnatal lung function or lung volumes did not improve for the 8-hour treatment-to-delivery interval, although betamethasone decreased the pulmonary edema and increased the postnatal blood pressure. CONCLUSIONS: The minimal interval from fetal exposure to corticosteroids to delivery for improved postnatal lung function was between 8 and 15 hours. Corticosteroid effects on pulmonary edema and blood pressure occurred within 8 hours.     

Short-term effects of flurbiprofen and diclofenac on refractive outcome and corneal haze after photorefractive keratectomy

PURPOSE: To evaluate the short-term effects of topical nonsteroidal anti-inflammatory drugs (NSAIDs) on refractive outcome and corneal haze after excimer laser photorefractive keratectomy (PRK) according to the degree of myopia and to compare the results with those of topical steroids. SETTING: Seoul National University Hospital, Seoul, Korea. METHODS: Patients were divided into two groups: low to moderate myopia (-6.00 diopters [D] or less) and high myopia (greater than 6.00 D). Then, each patient was randomly assigned to one of three drug subgroups for initial management (4 months post-PRK): corticosteroids (fluorometholone 0.1%); flurbiprofen sodium 0.03% (Ocufen); diclofenac sodium 0.1% (Decrol). Follow-up was 6 months. RESULTS: In eyes with low to moderate myopia, the steroid and diclofenac subgroups had significantly different refractions 2 and 4 months postoperatively but no difference at 6 months; subjective haze grading was consistently lower in the steroid subgroup than in the NSAID subgroups (flurbiprofen, diclofenac) after 2 months. In eyes with high myopia, the steroid subgroup had significantly less myopic regression after 3 weeks and lower subjective haze after 2 months than the NSAID subgroups. The steroid subgroup had severe myopic regression or corneal haze less frequently than the NSAID subgroups. CONCLUSION: Topical NSAIDs were less effective than topical steroids in reducing myopic regression and haze after PRK, especially in highly myopic eyes.     

Psychiatry and bioethics. An exploration of the relationship

The purpose of this study was to determine glucocorticoid modulation of ocular pressure to epinephrine applied topically to rabbit eyes that were pretreated with dexamethasone. Rabbit eyes were pretreated with five applications of topical 0.07% dexamethasone (0.1% dexamethasone phosphate) or saline drops, administered at ten minute intervals. The eyes were then treated with epinephrine bitartrate drops at concentrations of free base epinephrine of 1.1%, 0.27%, 0.05%, 0.027%, 0.005% or 0.0005%. An additional group of rabbits received dexamethasone pretreatment only. Intraocular pressure (IOP) was measured for the next four hours. Enhanced lowering of intraocular pressure was observed with dexamethasone pretreatment. Rabbits receiving the smaller dose of epinephrine with dexamethasone had the largest decrease in IOP at 135 minutes after instillation of the epinephrine drops (0.005% epinephrine, mean difference +/- standard error of mean = 5.4 +/- 1.1 mmHg). Similarly, the duration of significant decrease of the IOP was prolonged in the groups receiving the lower concentrations of epinephrine (0.005% epinephrine, 255 minutes after administration of epinephrine). The synergism between glucocorticoids and adrenergic agonists in lowering IOP may be potentially useful in the therapy of ocular hypertension and glaucoma.     

Topical laryngo-tracheal anesthesia and intraocular pressure in anesthesia for ophthalmic surgery

OBJECTIVE: The reflex response to orotracheal intubation provokes an increase of arterial pressure accompanied by an increase of chorioides volume and a consequent ocular hypertone. There are several methods to reduce the reflex response due to intubation. One of the most effective is topical anaesthesia of larynx and trachea. Experiments were directed to evaluate the efficacy of topical anaesthesia to reduce the intraocular hypertone due to orotracheal intubation. DESIGN: A prospective randomized mask study was conduct on patients undergoing ophthalmologic (anterior segment) surgery at the Eye Clinic of Florence University. METHODS: Intraocular pressure was measured by a Goldman tonometer at four times: T0 = basal, T1 = 2' minutes after induction of general anaesthesia, T2 = 2' minutes after laryngoscopy, T3 = 2' minutes after orotracheal intubation. At the same moments, systolic blood pressure, heart rate, rate pressure pro duct were measured. Patients were randomly divided in two groups: Group L (n = 10) in which was evaluated the efficacy of laryngotracheal topical spray of lidocaine 4% (2 ml) and Group F (n = 10) in which saline was used instead of anesthetic. The filling of the LTA kit (Abbott) was made by a person not involved in the experiments. DATA ANALYSIS: Student's t test for unpaired data. RESULTS: Topical anaesthesia reduces the increase of intraocular pressure, hypertension and rate pressure product due to intubation. The intraocular pressure reduces to 13% less than basal value in Group L and increase to 50% more than basal value in Group F. CONCLUSION: The topical anaesthesia of larynx and trachea is effective to reduce the intraocular hypertension due to the reflex response evoked by orotracheal intubation.     

The value of pancuronium in prolonged intraocular operations

We wished to determine the effectiveness of Pancuronium, a non-depolarizing muscle relaxant, in prolonged intraocular operations. We compared the variations in intraocular pressure when using four different methods of induction of general anesthesia. With Pancuronium the intraocular pressure fell initially and then rose to just below pre-induction levels and remained there. Our study suggests that pancuronium stabilizes intraocular pressure at a level which is highly desirable for intraocular surgery.     

Detection of myeloperoxidase by flow cytometry in acute leukemia

BACKGROUND: To evaluate long-term results of intraocular pressure after trabeculectomy for congenital glaucoma. METHODS: Data concerning 55 eyes (30 patients) who underwent trabeculectomy for congenital glaucoma were recorded. Mean age at diagnosis was 3.4 months (range: 2 days to 10 months). Mean follow up was 56.8 months. Associated anterior segment abnormalities, need for one or more new trabeculectomy procedures during follow up, and intraocular pressure at the last examination were noted. RESULTS: Of the 55 eyes, 48 met the success criteria (87.3%). A second and sometimes third or fourth trabeculectomy were necessary during follow up in 17 eyes (31%). Of the seven failures at final examination, six (85%) had been diagnosed and operated on before the age of 1 month, whereas 15 of the 48 eyes with good results (31.2%) were in this group (p < 0.02). Of the seven failures at final examination, six (85%) were operated on two to four times, whereas 10 of the 48 eyes with good results (20.1%) were in this group (p < 0.01). An associated anterior segment abnormality was present in 13 eyes (23%), and did not seem to influence the final outcome. CONCLUSION: Trabeculectomy is an effective procedure for long-term control of intraocular pressure in congenital glaucoma. The early diagnosis and surgical treatment correspond to a poor long-term prognosis, probably related to initially severe cases. In these cases, intraocular pressure is difficult to control despite repeated surgical procedures.     

Epidermal cell DNA content and intermediate filaments keratin 10 and vimentin after treatment of psoriasis with calcipotriol cream once daily, twice daily and in combination with clobetasone 17-butyrate cream or betamethasone 17-valerate cream: a comparative flow cytometric study

Calcipotriol and corticosteroids, two therapy modalities frequently prescribed in the treatment of psoriasis, are often used in combination. The aim of the present study was to determine whether the cell biological response pattern of concurrent use of calcipotriol and corticosteroids is different from calcipotriol monotherapy. Forty patients with chronic plaque psoriasis were divided at random in four parallel groups and treated for 8 weeks with: (1) calcipotriol cream (50 micrograms/g once daily); (2) calcipotriol cream twice daily; (3) calcipotriol and clobetasone 17-butyrate (0.5 mg/g) creams; and (4) calcipotriol and betamethasone 17-valerate (1 mg/g) creams. Before and after treatment keratotome biopsies were taken and single cell suspensions prepared for flow cytometric analysis. Flow cytometric multiparameter quantification of markers for proliferation (TO-PRO-3), differentiation (antikeratin 10) and inflammation (antivimentin) was used to evaluate all four therapy modalities. A statistically significant decrease of the percentage of basal cells in S- and G2M-phase (proliferation) was obtained with all therapy modalities, except for calcipotriol monotherapy applied once daily. A significant reduction of the number of vimentin-positive cells (non-keratinocytes) was observed following combined treatment with calcipotriol and clobetasone butyrate. In contrast, monotherapy with calcipotriol had virtually no effect on the number of vimentin-positive cells. It can be concluded that: (i) calcipotriol monotherapy, applied once daily was less antiproliferative compared with twice daily applications of calcipotriol or the combined treatment with corticosteroids and that (ii) the combination of calcipotriol and corticosteroids proved to have a marked effect on the percentage of non-keratinocytes, in contrast to the modest effect of calcipotriol.     

Effect of maternal betamethasone administration at midgestation on baboon fetal adrenal gland development and adrenocorticotropin receptor messenger ribonucleic acid expression

Although fetal pituitary ACTH is important to fetal adrenal growth and steroidogenesis in the second half of primate pregnancy, its role in adrenal development and function has not been established in vivo in the first half of gestation. In the present study, therefore, baboons were treated at midgestation with betamethasone to determine the effect of fetal pituitary ACTH on fetal adrenal growth, development, and ACTH receptor and P-450 enzyme messenger ribonucleic acid (mRNA) levels. The administration of betamethasone to baboon mothers on days 60-99 of gestation (term = 184 days) decreased fetal pituitary POMC mRNA levels by 54% (P < 0.01) and fetal serum ACTH levels to undetectable values (P < 0.05). The decline in ACTH was associated with decreases in fetal adrenal weight (P < 0.001), cortical cell size (P < 0.05), appearance of apoptosis and cellular disorganization, and a loss of immunocytochemically demonstrable definitive zone-specific delta5-3beta-hydroxysteroid dehydrogenase expression. The concomitant administration of ACTH and betamethasone restored these aspects of adrenal integrity to normal. Moreover, there was approximately a 95% decrease (P < 0.01) in fetal adrenal expression of ACTH receptor, P-450 cholesterol side-chain cleavage, and P-450 17alpha-hydroxylase 17/20-lyase mRNA levels after betamethasone administration. We conclude that fetal pituitary ACTH is necessary for the growth and development of fetal and definitive cortical zones and the marked coordinated increase in ACTH receptor and maintenance of P-450 cholesterol side-chain cleavage/P-450 17alpha-hydroxylase 17/20-lyase expression in the baboon fetal adrenal gland during the first half of gestation.     

Rapid verification of the identity of questionable specimens using immunohistochemistry with monoclonal antibodies directed against HLA-class I antigens

PURPOSE: To evaluate the effect of substituting topical cyclosporin A 0.5% for topical corticosteroids in patients with postkeratoplasty glaucoma. METHODS: Topical cyclosporin A 0.5% was prospectively substituted for topical corticosteroids to treat 25 patients with postkeratoplasty glaucoma. RESULTS: Twenty-one (84%) of 25 patients showed a reduction in intraocular pressure (IOP) (range, 1-22 mm Hg; mean, 8.7 mm Hg). Follow-up ranged from 3 to 12 months (mean, 5.8). Graft clarity was maintained in all patients, with one allograft rejection episode. Thirteen patients were able to discontinue one or more glaucoma medication(s). CONCLUSION: Topical cyclosporin A 0.5% may be substituted for topical corticosteroids to aid in the management of postkeratoplasty patients with glaucoma. However, the resultant decrease in IOP may be associated with an increased risk for immune rejections.     

Evaluation of intraocular pressure and cataract formation following the long-term use of nasal corticosteroids

It is possible that corticosteroids administered via nasal spray might reach ocular structures in levels sufficient to provoke an ocular hypertensive response and cause posterior subcapsular cataracts (PSCs) in susceptible individuals. In the present study, 26 patients who had undergone endoscopic sinus surgery were evaluated prospectively with respect to intraocular pressure and PSC formation following the use of nasal steroids for at least three months. Eighteen patients (69%) self-administered 200 micrograms/day of budesonide nasal spray twice daily, and eight patients (31%) self-administered 200 micrograms/day of beclomethasone dipropionate nasal spray twice daily, for a period of three to 19 months (mean 8.8 +/- 3.6 months). Ophthalmologic examination, tonometry, visual field testing and biomicroscopic studies revealed no evidence of ocular hypertension or PSCs during postoperative follow-up. We conclude that intranasal corticosteroids can be used safely for prolonged periods without increasing the risk of ocular hypertension or PSCs.     

Treatment of persistent glaucoma secondary to periocular corticosteroids

PURPOSE: To describe two patients with uveitis who developed increased intraocular pressure that was unresponsive to maximum medical therapy eight and 13 months after periocular injection of triamcinolone acetonide. METHODS: Excised periocular tissue was analyzed for corticosteroid activity by gas chromatography and mass spectrometry. RESULTS: Excision of the periocular tissue, which contained visible triamcinolone acetonide, resulted in a normal intraocular pressure within 14 days in both patients. Analysis of the excised tissue disclosed residual corticosteroid in one of the two patients. CONCLUSION: Removal of periocular tissue containing injected corticosteroids may facilitate the management of patients developing increased intraocular pressure unresponsive to maximum medical therapy.     

Intraocular irritation evaluation of benzalkonium chloride in rabbits

The purpose of this study was to define the threshold for intraocular irritation of benzalkonium chloride, a preservative used in some formulations which enter the anterior segment of the eye during ocular surgery. Various concentrations of benzalkonium were injected into anterior chambers of albino rabbit eyes. Conjunctivitis, flare, iritis, and corneal changes occurred in a dose response pattern. The threshold of irritation was 0.03%, with highest nonirritating concentration being 0.01%. In other works in this laboratory, threshold of irritation for topical ocular benzalkonium was 0.05%, but the nature of ocular changes was less substantial than those observed intraocularly. Because the threshold for intraocular irritation is less than that topically, the nature of ocular changes was different for two routes, and there is a paucity of clinical data for intraocular benzalkonium chloride, a safety factor of 10 was utilized in setting the highest safe concentration of 0.001% for intraocular use. The preservative efficacy of 0.001% is questionable; therefore, we cannot endorse benzalkonium chloride as a preservative for formulations which will enter the anterior segment of the eye.     

Normalization of low vitamin B12 serum levels in older people by oral treatment

PURPOSE: To report the potential for retinal ischemia caused by high intraocular pressure and to suggest a simple test for this condition. METHODS: We measured the intraocular pressure and directly examined the optic nerve head in four eyes of four patients at the conclusion of cataract surgery. RESULTS: With intraocular pressure above 40 mm Hg, elderly patients may abruptly lose the ability to perceive microscope illumination. The central retinal artery pulsated at these pressures. Light perception returned immediately upon reduction of intraocular pressure. CONCLUSION: Testing for light perception at the conclusion of surgery can indicate retinal ischemia with loss of light perception, which may occur during sealing of the cataract surgical wound.     

First trimester isolated fetal nuchal lucency: significance and outcome

BACKGROUND: In this retrospective study the postoperative alteration of intraocular pressure after cataract extraction and posterior chamber lens implantation was analyzed statistically. The influence on intraocular pressure between different positions of the loops (sulcus versus bag) was compared. PATIENTS AND METHOD: The posterior chamber lens implantation was performed on 267 eyes with 129 sulcus implanted and 138 in-the-bag implanted intraocular lenses. The average age of the patients was 74.8 respectively 71.9 years, with an equal ratio of sex. In surgery the viscoelastic experimentation of the nucleus was done via corneoscleral cut. A x-crossed suture sealed the corneoscleral wound followed by subconjunctival injection of corticosteroids. The postoperative medication for 4-6 weeks consisted of a corticosteroid and antibiotic combination. RESULTS: The average intraocular pressure of the sulcus implanted respectively in the bag implanted intraocular lenses increased from 15.4 mm Hg respectively 15.9 mm Hg preoperatively to 16.3 respectively 15.8 mm Hg at the first postoperative day. After two months the intraocular pressure decreased to 14.6 respectively 14.1 mm Hg. That means a pre- to postoperative difference of -0.8 respectively -1.8 mm Hg. CONCLUSIONS: In summary both groups showed a slight decrease in average intraocular pressure after two months. In comparison to the sulcus implanted intraocular lens the decrease of intraocular pressure was more than 1 mm Hg in case of the in the bag implanted lens. This decrease was statistically significant but may be considered of less clinical interest.