Fall In IOP Research Articles

A Pharmacoeconomic Analysis to Determine the Relative Cost-effectiveness of Timolol 0.5%, Brinzolamide 1% and Brimonidine 0.2% Eye Drops in Treatment of Primary Open Angle Glaucoma/Ocular Hypertension

Aim: A pharmacoeconomic analysis to determine the relative cost-effectiveness of timolol 0.5%, brinzolamide 1% and brimonidine 0.2% eye drops in treatment of Primary Open Angle Glaucoma (POAG)/ocular hypertension (OHT). Settings and Design: Comparative, open, randomized, parallel group prospective study. Materials and Methods: 60 patients of POAG or ocular hypertension were included in this study. Time period of study was 6 weeks. 60 eyes of 60 patients were included in the study. Patients were divided randomly into 3 groups of 20 each. Patients in group A, B and C received timolol, brinzolamide and brimonidine respectively. One drop of each medication was instilled twice a day at 9 am and 9 pm daily for 6 weeks. IOP was measured on day 0 at 9 am (before administration of drugs) and then at 11 am, to get baseline IOP. IOP was again measured on subsequent visits at 9 am and 11 am. Treatment outcome was number of mm Hg fall in IOP induced by the study drug. The daily cost of each drug was calculated by maximum retail price and the average number of drops per bottle. The cost‑effectiveness was then calculated as the cost of drug/mm Hg fall in IOP. Statistics: Paired ‘t’ test was used to analyze the parameters within the group. Independent samples t‑test was used to compare the efficacy of drugs with each other. Results: The % reduction of brimonidine, timolol and brinzolamide at end of 6 weeks was 21.43 ± 3.06%, 24.87 ± 2.46% and 18.78 ± 1.73% respectively. Timolol was superior in efficacy to other two drugs. The difference was statistically significant between the efficacy of timolol and brinzolamide (p < 0.001) as well as timolol and brimonidine (p = 0.003). There was no statistical significant difference in the efficacy of brimonidine when compared to brinzolamide (p=0.26). Timolol (5.87 ± 0.83 Rs/mm lowering after 6 weeks) was found to be most cost-effective followed by brimonidine (46.83 ± 7.37) and then brinzolamide (60.49 ± 6.77) in lowering IOP. Conclusion: All three drugs under the present study are useful in the treatment of POAG/OHT, but timolol is a better choice than other two drugs because of greater reduction in IOP and greater cost-effectiveness.

A Rare Case Report of Unilateral Congenital Ectropion Uveae (CEU) with Iridotrabecular Dysgenesis, Juvenile Glaucoma and Ptosis

Congenital ectropion uveae is a rare disorder resulting from proliferation of iris pigment epithelium on the anterior surface of iris. We describe a case of a 28-year-old female presenting with diminution of vision in the left eye. She was using topical drugs for high intraocular pressure. On examination, visual acuity was 20/60. There was mild ptosis present along with ectropion uveae, 360 degrees around the pupillary border. Intraocular pressure was 32 mm Hg. On fundoscopy, there was glaucomatous cupping with superior notching of the disc. Gonioscopy revealed an open angle with anterior insertion of iris over trabecular meshwork. Visual field analysis showed inferior arcuate scotoma. Examination of the right eye revealed no abnormality and visual acuity was 20/20. No systemic illness was found. The fall in IOP in the left eye following medical treatment remained unsatisfactory. Hence, trabeculectomy was performed. Following a period of 3 months post trabeculectomy, control of IOP was achieved (15 mm Hg). It is important to evaluate for glaucoma in congenital ectropion uveae cases to prevent blindness in young patients and improve their prognosis.

Temperature oscillations drive cycles in the activity of MMP-2,9 secreted by a human trabecular meshwork cell line.

Aqueous humor inflow falls 50% during sleeping hours without proportional fall in IOP, partly reflecting reduced outflow facility. The mechanisms underlying outflow facility cycling are unknown. One outflow facility regulator is matrix metalloproteinase (MMP) release from trabecular meshwork (TM) cells. Because anterior segment temperature must oscillate due to core temperature cycling and eyelid closure during sleep, we tested whether physiologically relevant temperature oscillations drive cycles in the activity of secreted MMP. Temperature of transformed normal human TM cells (hTM5 line) was fixed or alternated 12 hours/12 hours between 33°C and 37°C. Activity of secreted MMP-2 and MMP-9 was measured by zymography, and gene expression by RT-PCR and quantitative PCR. Raising temperature to 37°C increased, and lowering to 33°C reduced, activity of secreted MMP. Switching between 37°C and 33°C altered MMP-9 by 40% ± 3% and MMP-2 by 22% ± 2%. Peripheral circadian clocks did not mediate temperature-driven cycling of MMP secretion because MMP-release oscillations did not persist at constant temperature after 3 to 6 days of alternating temperatures, and temperature cycles did not entrain clock-gene expression in these cells. Furthermore, inhibiting heat shock transcription factor 1, which links temperature and peripheral clock-gene oscillations, inhibited MMP-9 but not MMP-2 temperature-driven MMP cycling. Inhibition of heat-sensitive TRPV1 channels altered total MMP secretion but not temperature-induced modulations. Inhibiting cold-sensitive TRPM-8 channels had no effect. Physiologically relevant temperature oscillations drive fluctuations of secreted MMP-2 and MMP-9 activity in hTM5 cells independent of peripheral clock genes and temperature-sensitive TRP channels.

A Prospective Study to Analyse the efficacy of Apraclonidine in Preventing Intraocular Pressure Rise After Neodymium: YAG (Nd-YAG) Laser Posterior Capsulotomy

Objective: To analyse the efficacy of (0.5%) apraclonidine in preventing the acute rise of intraocular pressure following Nd-YAG Laser posterior capsulotomy. Material and method: A prospective case controlled randomised study was performed in the department of ophthalmology of SIMS in collaboration of department of pharmacology. Result: A total 52 patients were divided in two groups. Half of the patients were given 0.5% topical apraclonidine 15 minutes before the procedure and immediately after the procedure and after 1 hr, 2hr, and 4hrs respectively. The other half were not given any IOP lowering drug.IOP was measured by tonometry. There was significant fall in IOP in test group patients. IOP in two groups 1hr after procedure was 13.08% rise in control and 6.40% fall in test group. Conclusion: Apraclonidine, a highly selective alpha2 adrenoceptor agonist effectively and safely lowers IOP spikes after laser treatment without causing significant side effects like bradycardia or hypotension.

Intraocular pressure changes following laryngoscopy and intubation- McCoy versus Macintosh laryngoscope

Background We compared intraocular pressure changes following laryngoscopy and intubation with conventional Macintosh blade and McCoy laryngoscope. Methods Sixty adult patients were randomly assigned to study group or control group. Study group - (Group A, n=30) - McCoy laryngoscope was used for laryngoscopy. Control group (Group B, n=30) - conventional Macintosh laryngoscope was used for laryngoscopy. Pre-medication was given in the form of tablet alprazolam 0.25mg orally at bed time and two hours prior to surgery. Preoperative baseline intraocular pressure was measured with Schiotz tonometer after instillation of 4% xylocaine drops in the right eye. Injection thiopentone sodium 5 mgkg-1 over 20 seconds was used for induction followed by injection vecuronium 0.1mgkg-1 for intubation. All patients were manually ventilated using oxygen 33%, nitrous oxide 67% and halothane 0.5% for three minutes and ETCO 2 was kept below 40mmHg. Laryngoscopy was done as per group protocol. Size 7mm ID cuffed endotracheal tube was used for female patients and size 8mm ID for male patients in both the groups. Intraocular pressure and haemodynamic parameters were recorded just before induction of anaesthesia (baseline), just before laryngoscopy and intubation and 1 and 3 minutes after intubation. Results Patient characteristics, baseline haemodynamic parameters and baseline IOP were comparable in the two groups. Following induction (T 0 ), there was statistically significant fall in IOP in both groups. One minute after intubation (T 1 ), there was significant rise in IOP in both the groups and remained so even at three minutes after intubation (T 3 ). When compared in between the groups at one minute after intubation, the rise in intraocular pressure was significantly less in the study group (A). Conclusion We conclude that McCoy laryngoscope in comparison to Macintosh laryngoscope results in significantly less rise in IOP and clinically less marked increase in haemodynamic response to laryngoscopy and intubation. DOI: http://dx.doi.org/10.4038/slja.v20i2.3213 Sri Lankan Journal of Anaesthesiology. 2012:20(2):73-77

Decompression Retinopathy after Trabeculectomy

To present a case of a unilateral diffuse retinal hemorrhage in a 15-year-old girl, who underwent bilateral trabeculectomy for steroid induced glaucoma. Despite the maximally tolerable medical treatment, IOP in the right eye remained above 50 mmHg for four months, and was simultaneously elevated in the left eye. So we performed bilateral trabeculectomy. On the first postoperative day, diffuse retinal hemorrhages were observed in the right eye; however, no retinal hemorrhage was found in the left eye. The hemorrhages resolved completely without consequences two months later. In the case of high IOP for a long period, sudden lowering of IOP may acutely increase the blood flow and consequently rupture multiple retinal capillaries because of altered autoregulatory function. Special care is therefore needed to prevent an abrupt fall in IOP before, during, and after surgery, especially when IOP has been highly elevated for an extended period.

Glaucoma surgery with or without adjunctive antiproliferatives in normal tension glaucoma: 2. Visual field progression.

Studies have shown that a reduction of intraocular pressure by 20 percent to 30 percent with glaucoma filtering surgery slows disease progression in normal tension glaucoma (NTG). These authors further investigated whether adjunctive antiproliferative agents are necessary or safe in eyes at low risk for scarring. White patients (61 eyes in 61 patients) with NTG who had undergone a primary guarded filtration procedure were reviewed: 20 eyes had no antiproliferatives (none), 29 had perioperative 5-fluorouracil (5-FU), and 12 had perioperative mitomycin C (MMC). Point wise linear regression analysis was applied to their visual field series starting with the first visual field following surgery and adding subsequent visual fields one at a time. Progression of visual field loss was defined as the appearance of a regression slope 1 dB per year or more with a significance of P < 0.01 at one or more visual field locations that remained consistent with the addition of two of three successive visual fields. The median percentage IOP reduction was 24.4 for the none group, 38.0 for the 5-FU group, and 47.5 for the MMC group (P = 0.001). There was a statistically significant relation between percentage change in IOP and risk of visual field progression in the subsequent 6-month period for all patients analyzed as one group. There was a statistically significantly increase in the risk of visual field progression for the MMC group compared with the 5-FU group. The authors conclude that in NTG patients, the IOP reduction produced by filtering surgery reduces the risk that visual field progression. The percentage drop in IOP during a given time is related to the risk of subsequent visual field progression. However, the use of MMC is associated with a greater risk of visual field progression despite a greater fall in IOP. This visual field deterioration may be related to the functional loss produced by late postoperative complications that have been reported at a higher rate in this group. The use of adjunctive perioperative 5-FU should maintain a suitable target IOP with preservation of visual function without the additional complications and associated visual deterioration seen with adjunctive MMC.—Thomas J. Liesegang

Glaucoma surgery with or without adjunctive antiproliferatives in normal tension glaucoma: 2 Visual field progression

BACKGROUNDReduction of intraocular pressure by 20–30% with glaucoma drainage surgery slows disease progression in normal tension glaucoma (NTG). It is not clear whether adjunctive antiproliferative agents are necessary or safe...

The Long-Term Effect on Intraocular Pressure of a Procedure Combining Trabeculectomy and Cataract Surgery, as Compared With Trabeculectomy Alone

The long-term reduction of intraocular pressure (IOP) resulting from a procedure combining extracapsular cataract extraction and posterior chamber lens implantation with trabeculectomy was compared retrospectively with the IOP-lowering effect of trabeculectomy alone. Forty patients who underwent the combined procedure and 38 who underwent trabeculectomy alone had been followed for an average of 22 +/- 7 months. Both these surgical procedures significantly reduced IOP, but after a year or more, pressure levels were significantly lower in the trabeculectomy group than they were in the combined group: 12.8 +/- 4.2 mm Hg, and 16.5 +/- 5.6 mm Hg, respectively, at 18 months. Also, the mean postoperative fall in IOP was greater in the "filtered" eyes than it was in the combined group (9.8 +/- 4.6 mm Hg and 12.1 +/- 5.2 mm Hg, respectively, at 18 months). Finally, the number of medications required to maintain controlled IOP in the combined group was greater (and resumed preoperative values at 2 years) than it was in the trabeculectomy group (62.5% of the filtered eyes remained controlled unaided).

ARGON LASER TRABECULOPLASTY FIVE YEARS ON

The results of argon laser trabeculoplasty (ALT) in a series of 252 patients are presented with follow-up of up to five years. The procedure is effective in chronic open-angle glaucoma (COAG), ocular hypertension and pseudoexfoliative (PXF) glaucoma. Most cases were treated initially over 180 degrees of the angle and repeat treatment of the remaining 180 degrees usually resulted in an additional fall in IOP which was maintained at two, three and four year follow-up with only a small number of these retreated cases having no fall on later follow-up. ALT was not very effective in further lowering IOP in eyes with IOP controlled to a low level before treatment or in low tension glaucoma. It was effective in most of a number of miscellaneous glaucomas including pigmentary glaucoma. Apart from the immediate high rise in IOP the main complication was a late high rise in IOP which was serious in degree and appeared mainly in PXF but also in two cases of ocular hypertension. The presence of a concomitant fall in IOP in the fellow untreated eye is important and probably due to better compliance with treatment. Almost all cases required medical treatment for glaucoma which could not be ceased after ALT. ALT should be seen as an adjunct to, but not a substitute for, medical treatment.

Demonstration of the tonographic effect in YAG laser trabeculoplasty in chronic glaucoma

In a pilot study comprising 16 eyes of 16 patients with chronic open-angle glaucoma the tonographic outflow facility was examined before and after Nd-YAG laser treatment of the trabecular meshwork. For evaluation of the facility effect of laser trabeculoplasty, the tonographic record between the third and seventh minute according to the tonography test of Leydhecker was used. An improvement in outflow facility was established which correlated with the postoperative fall in IOP.

Postjunctional adrenergic receptors in the rabbit eye: effects on uveal flow and intraocular pressure in isolated arterially perfused eyes.

In uveal vessels of isolated arterially perfused rabbit eyes there is direct evidence for the presence of post-junctional alpha 1-receptors and indirect evidence for alpha 2-receptors. Since vasoconstriction by epinephrine could not be blocked by an alpha 1-antagonist, only 30% by an alpha 2-antagonist and almost fully by the combination or by phentolamine, we suggest the presence of an intermediate alpha-type receptor which is neither alpha 1 nor alpha 2 but has characteristics of either. All alpha-types produce vasoconstriction and a fall in IOP. Of the beta-types only beta 1-receptors can be demonstrated. They mediate vasodilatation and a rise in IOP. Neither beta 2- nor non-selective beta-agonists or -antagonists (e.g. timolol) affect IOP or uveal flow.

Medical therapy for experimental hypotony.

Experimental hypotony was induced in rhesus monkeys by the following procedures: ciliochoroidal detachment, retinal detachment, or cyclodialysis. Two days later, at the time of greatest hypotony, 10% methacholine chloride was deposited in the cornea by iontophoresis, and 0.25% physostigmine salicylate ointment was applied topically to each eye. The intraocular pressure rose to normal levels in all eyes for eight to 24 hours. The peak rise in IOP occurred one to four hours after drug administration and was 7.2, 6.8, and 11.3 mm Hg higher than the pretreatment levels in eyes with ciliochoroidal detachment, retinal detachment, and cyclodialysis, respectively. In a group of normal eyes, this drug combination caused a transient 5.7 mm Hg fall in IOP. The mechanism of pressure elevation by methacholine and physostigmine probably is caused by stimulation of aqueous humor formation or reduced uveoscleral outflow, or both.

Ocular hypertensive response to beta-adrenoceptor agonists.

Acute administration of non-selective and relatively selective beta-adrenoceptor agonists elicit a monophasic fall in IOP. The present study indicates that unilateral application of certain beta-agonists on consecutive days can result in marked ocular hypertension. 1-Epinephrine, reproterol and 1-isoproterenol evoked an elevation of IOP on the second and third day after topical administration of a 2% solution in normal rabbits and in rabbits with surgically transected extraocular muscles. In contrast, the same concentration of d-isoproterenol produced hypotensive responses only when administered once daily for three consecutive days. Since d-isoproterenol did not cause a rise in IOP during chronic administration, the mechanism involved in the hypertensive response appears to be more sensitive to the levorotatory form. Administration of timolol inhibited the ocular hypertensive effect of epinephrine and reproterol. Since timolol lowers IOP by depressing formation of aqueous, it is suggested that the rise in IOP following chronic administration of beta-agonists possibly involves an increase in aqueous humor production.

Effect of changes in PCO2 and body positions on intraocular pressure during general anaesthesia.

Elevated arterial carbon dioxide tension, induced by the administration of CO2 via the respiratory air or by hypoventilation, entailed a gradual increase in the IOP in patients without eye diseases under general anaesthesia. A sudden cessation of CO2 administration or hyperventilation caused such a rapid, simultaneous fall in IOP to values below the initial level that the pressure variations must be of vascular nature, presumably related to changes in choroidal blood volume. The above-mentioned procedures always cause a change in the central venous pressure (CVP) simultaneously with the IOP changes. Alterations of the CVP induced by hydrostatic factors in postural changes, placing the head 15 degrees above or below the horizontal level while keeping the PaCO2 constant, caused IOP changes of the same configuration and magnitude as described above. It is concluded, therefore, that presumably the CO2-conditioned IOP changes are due predominantly to changes in central venous pressure, being one link in a CO2-conditioned action upon the general circulation, entailing passive secondary changes in the choroidal venous blood volume and thereby an influence upon the IOP. On the basis of the present results it appears rational to recommend hyperventilation to keep the PaCO2 between 25 and 30 mm and a 15 degree anti-Trendelenburg position in operations on the eye under general anaesthesia, since both procedures afford a low central venous pressure and consequently a low pressure in the posterior segment of the eye, with its attendant advantages as regards vitreous complications and the insertion of intraocular lenses. Owing to the risk of an unacceptable fall in BP in the combined procedure, a frequent checking of the BP is needed.

The effects of topically applied epinephrine and timolol on intraocular pressure and aqueous humor cyclic-AMP in the rabbit

Intraocular pressure and aqueous humor cyclic-AMP concentrations were measured in albino rabbits following topical treatment of one eye with a single dose of 2% epinephrine alone, 0·5% timolol alone, or epinephrine after timolol pretreatment. Most animals demonstrated a significant hypotensive response 6 hr after epinephrine treatment, which lasted at least an additional 6 hr. However, aqueous humor c-AMP was significantly elevated 30 min after epinephrine treatment, peaked between 60 and 240 min, and declined to baseline by 6 hr before a significant ocular hypotensive response was noted. Timolol treatment alone had no significant effect on either intraocular pressure or aqueous c-AMP. However, in epinephrine-treated animals which were pre-treated with timolol, the c-AMP response was blocked, with no significant alteration of the hypotensive response. Previous reports in the literature suggested a causal relationship between elevated aqueous humor c-AMP and fall in IOP. On the basis of the present work, this relationship is questionable.

The influence of drugs on intra-ocular pressure, mediated by the central nervous system

The influence of drugs on intra-ocular pressure, mediated by the central nervous system

The influence of acute and chronic cervical sympathectomy on the ocular hypotensive effect of clonidine

The influence of clonidine on intraocular pressure was studied in chloralose-anesthetized cats. The cats were subjected to unilateral cervical sympathectomy, either acute or chronic. The drug was injected either intravenously or into the left vertebral artery. With the aim of investigating the role of the sympathetic nervous system in the central IOP-lowering effect of clonidine, the fall in IOP induced by the drug in these preparations was compared to the decrease in ocular pressure caused by clonidine in intact cats. An enhanced depressor effect in both eyes of unilaterally sympathectomized cats became evident after the intravenous injection of clonidine. In contrast, the effect of central administration was similar or even smaller than in intact cats. We conclude that the central IOP-lowering effect of clonidine is diminished after cervical sympathectomy, indicating that the peripheral sympathetic nervous system is the efferent pathway of this centrally initiated effect.

Metoprolol eye drops in the treatment of glaucoma a double-blind single-dose trial of a beta1-adrenergic bloking drug

A double-blind single-dose trial was performed on 13 patients with primary open-angle glaucoma. Metoprolol 1%, 2%, and 4% produced a median fall in IOP of 5.6, 5.4, and 6.8 mm Hg, respectively, in the treated eye. The differences in effect between the 1%, 2%, and 4% solutions were not statistically significant. There was no significant fall in IOP in the untreated eyes. There were no significant changes in blood pressure, pulse rate, or pupillary diameter. We could not detect any local objective or subjective side effects during the single-dose study. The clinical usefulness of metoprolol may be limited due to local toxic reactions after treatment with multiple doses. Furthermore, there is the problem of tachyphylaxis that could limit extended treatment with topical beta-adrenergic blocking drugs.