Retinal Detachments Associated With Topical Pilocarpine Use for Presbyopia.

PURPOSE: To present a case series of retinal detachments associated with the use of pilocarpine for presbyopia. DESIGN: Multicenter case series of 3 eyes from 2 patients. RESULTS: Patient 1, a 47-year-old man, presented with flashes and floaters in both eyes. The patient had started pilocarpine 1.25% drops 1 month prior for presbyopia in both eyes. He noted the onset of flashes and floaters 3 days after he initiated the drops. A dilated examination revealed an inferotemporal retinal detachment in the right eye with an associated retinal tear inferotemporally. The left eye demonstrated a retinal detachment in the superior quadrant with an associated horseshoe tear at 12 o'clock. Patient 2, a 46-year-old man, presented 5 weeks after initiating topical pilocarpine 1.25% drops for presbyopia. He noted a nasal visual field defect in his left eye that progressed to include his central vision. A dilated examination revealed a superior retinal detachment from 11 to 3 o'clock with subretinal fluid extending into the macula. CONCLUSIONS: Pilocarpine and other miotics have long been suspected to be associated with an increased risk of retinal detachment. Prior to prescribing pilocarpine for presbyopia, physicians should inform patients of this potential adverse event and consider that these patients undergo a screening dilated examination, particularly if they are myopic, to determine if they are at higher risk for retinal detachment. Before the initiation of therapy, patients should be appropriately informed regarding symptoms of retinal tears or detachment, which include flashes, floaters, and visual field loss.

Controversies in Glaucoma: Current Medical Treatment and Drug Development.

Elevated eye pressure is the main risk factor for glaucoma; intraocular pressure rises when the ratio between aqueous humor formation (inflow) and its outflow is unbalanced. Currently, the main goal of medical treatment is the reduction of intraocular pressure. Five main classes of topical drugs are available; they include betablockers, carbonic anhydrase inhibitors, prostaglandin derivatives, sympathomimetics and miotics. Beta-blockers and carbonic anhydrase inhibitors slow the formation of aqueous humor and may be considered as "inflow" drugs; the other three classes reduce the resistance to the drainage of aqueous humor and may be considered as "outflow" drugs. Despite the variety of drugs accessible in the market, there is a real need for ophthalmologists to have more potent medications for this disease. This review focuses on medical treatment of glaucoma with particular attention to novel molecules in pre-clinical or clinical development.

Effect of intracameral carbachol in phacoemulsification surgery on macular morphology and retinal vessel caliber.

OBJECTIVE: To investigate the effects of intracameral carbachol in phacoemulsification surgery on central macular thickness (CMT), total macular volume (TMV) and retinal vessel caliber (RVC). MATERIALS AND METHODS: In this prospective consecutive case series, 82 patients underwent uneventful phacoemulsification and in-the-bag intraocular lens implantation. Unlike patients in the control group (43 eyes), patients in the study group (42 eyes) were injected with intracameral 0.01% carbachol during surgery. Spectral-domain optical coherence tomography (OCT) was used to analyze the parameters of CMT, TMV and RVC. RESULTS: On the first postoperative day, mean CMT and TMV decreased markedly in the carbachol group, though these values did not change significantly in the control group. During follow-up visits, no statistically significant differences between the groups occurred regarding changes in mean CMT (p = 0.25, first day; p = 0.80, first week; p = 0.95, first month). However, change in mean TMV between groups on the first postoperative day was statistically significant (p = 0.01, first day; p = 0.96, first week; p = 0.68, first month). RVC values were similar on the preoperative and postoperative first days in both groups (p > 0.05). DISCUSSION: Results suggest that the effect of intracameral carbachol on macular OCT is related to pharmacological effects, as well as optic events (e.g. miosis). CONCLUSION: Intracameral carbachol given during cataract surgery decreases macular thickness and volume in the early postoperative period but does not exert any gross effect on RVC.

[What should we think? Should Diamox and pilocarpine continue to be prescribed?]. / Que faut-il en penser? Le Diamox et la pilocarpine doivent-ils encore être prescrits?

Despite well-known adverse effects, pilocarpine and acetazolamide remain useful medications for the therapeutic management of glaucomatous patients.

[Ocular side effects of glaucoma treatment agents]. / Les effets secondaires des antiglaucomateux.

Antiglaucomatous ocular side effects can be divided into specific and non specific ones. Non specific ocular side effects are mainly caused by preservative agents; they are essentially external ocular irritations. Specific ocular side effects are strongly related to the mechanism of action of the drug. These specific ocular side effects are described, caution being taken to precise the strength of the association between each side effect and the related drug by using the classification of World Health Organisation (WHO) (certain, probable, possible or unlikely).

Cataractous changes due to posterior chamber flattening with a posterior chamber phakic intraocular lens secondary to the administration of pilocarpine.

OBJECTIVE: To present the first reported case of cataract formation as a consequence of instillation of pilocarpine in an eye with a posterior chamber phakic intraocular lens (IOL). DESIGN: Interventional case report. INTERVENTION: A 46-year-old man received a hyperopic implantable collamer lens (ICL) bilaterally. MAIN OUTCOME MEASURES: Determination of best-corrected visual acuity (BCVA); contrast sensitivity testing with and without glare; and intraocular pressure (IOP), specular endothelial cell, and slit-lamp examinations were performed serially. In addition, the distance between the ICL and crystalline lens was measured with optical coherence tomography. RESULTS: Both eyes underwent uneventful ICL implantation for the correction of a manifest spherical equivalent of +7 diopters (D) in the right eye and +7.1 D in the left eye. The left eye was followed for 2 years without developing complications. The right eye, however, showed on the first postoperative day a fleckenlike opacification on the anterior pole of the crystalline lens after instillation on the operative day of 2% pilocarpine in an attempt to accelerate recovery from unwanted pupil dilation causing patient complaints of glare disability after surgery. Optical coherence tomography demonstrated complete contact of the ICL with the natural lens 24 hours postoperatively. Serial IOP measurements were always within the normal limits. The instillation of 1% cyclopentolate resulted in an increase in the ICL vault that measured 132 mum 24 hours later. Three days after the completion of a 3-day course of topical 1% cyclopentolate, the opacification was less dense and demarcated, and a 124-mum vault was measured. Three months postoperatively, the cataract was associated with a 3-line loss of BCVA and considerable degradation of the contrast sensitivity, especially at higher spatial frequencies and with a glare source, and corneal endothelial cell changes were within normal limits. One year after ICL implantation, the right eye had to undergo phacoemulsification and IOL implantation, which were uneventful. CONCLUSIONS: Posterior chamber flattening with resulting crystalline lens opacification can occur immediately after the instillation of pilocarpine in an eye with a hyperopic ICL. Therefore, caution should be taken with the administration of cholinergic agonists such as pilocarpine in patients with phakic IOLs, at least if they are hyperopic ICLs.

Pilocarpine-induced shift of an accommodating intraocular lens: AT-45 Crystalens.

PURPOSE: To measure the shift of an accommodating plate-haptic intraocular lens (IOL) along the visual axis induced by ciliary muscle contraction after application of pilocarpine. SETTING: Department of Ophthalmology, Medical University of Vienna, Vienna, Austria. METHODS: Fifty-four eyes of 28 patients with age-related cataract comprised this prospective study. Each patient received an AT-45 silicone accommodating IOL (Crystalens, Eyeonics Corp.) after standardized cataract surgery. In a subgroup of 24 eyes, capsular bag fibrosis was reduced by extensive polishing of the anterior capsule with a slit cannula. Assessment included measurements of anterior chamber depth, assessed with partial coherence interferometry, before and after application of pilocarpine 2% and evaluation of near visual acuity 1 month and 3 months postoperatively. RESULTS: A slight backward shift of the IOL of 151 mum in the nonpolished group (P < .001) and 122 mum in the polished group (P < .005) could be detected after application of pilocarpine. Polishing the capsule did not influence IOL shift. The median near visual acuity with distance correction 1 month and 3 months postoperatively was J5 and J4, respectively, in the nonpolished group and J6 at both times in the polished group. CONCLUSIONS: Pilocarpine induced a counterproductive active backward shift of the AT-45 IOL. Polishing of the capsular bag had no impact on accommodative ability. The reading performance of patients with the AT-45 IOL patients at 1 and 3 months was not significantly different from that of with a standard IOL under similar testing methods.

Glaucoma pharmacotherapy: implications for flying fitness.

The objective of lowering the intraocular pressures remains the main-stay of therapy in the management of glaucoma, and may be achieved by medication, laser, or surgery. For many years the pharmacotherapy available, while quite effective, were few in number; principally timolol, pilocarpine, and oral acetazolamide. Through extensive research in glaucoma treatment, ophthalmologists now have access to a dozen different medications to treat glaucoma. This has invariably led to a decrease in the need for laser or surgery to control the intraocular pressures, and the number of glaucoma operations performed has progressively declined over the past few years. However, aviation medicine practitioners need to be aware of the potential adverse effects of these medications as some of these undesirable side effects may render the drugs unsuitable for aircrew.

Oral pilocarpine for the treatment of ocular symptoms in patients with Sjögren's syndrome: a randomised 12 week controlled study.

OBJECTIVE: To evaluate the efficacy and side effects of oral pilocarpine for the treatment of ocular symptoms in patients with primary Sjögren's syndrome (SS). METHODS: A 12 week, single centre, randomised controlled study was performed. Twenty nine patients were randomly assigned to receive oral pilocarpine (5 mg twice a day), 28 only artificial tears, and 28 inferior puncta occlusion. Patients receiving oral pilocarpine and those with inferior puncta occlusion also received artificial tears. Patients were evaluated at baseline and throughout the study for their subjective global assessment of dry eyes and for their objective assessment of dry eyes (Schirmer's-I test, rose bengal test, and imprint test). RESULTS: Patients taking oral pilocarpine had significant improvement in subjective global assessment of dry eyes, as was evaluated by improvement of >55 mm on a visual analogue scale (VAS) for responses to the eye questionnaire, compared with patients treated with artificial tears (p<0.001) and those with inferior puncta occlusion (p<0.05). Furthermore, patients receiving oral pilocarpine also showed greater objective improvement, as measured by the rose bengal test (p<0.05), while Schirmer's-I test showed no differences between the treated groups. Commonly reported adverse events were headache, increased sweating, nausea, and vomiting in the pilocarpine group, while one patient in the inferior puncta occlusion group had blepharitis and was withdrawn from the study. CONCLUSION: 10 mg of pilocarpine daily given to patients with SS for 12 weeks had a beneficial effect on subjective eye symptoms, as evaluated by improvement >55 mm on a VAS. Additionally, an improvement of rose bengal staining was noted, but an increase in tear production, as measured by the Schirmer-I test, was not substantiated.

[The medical treatment of glaucoma].

Chronic open angle glaucoma is a one of the leading causes of irreversible blindness. Elevated intraocular pressure is a major risk factor for the progression of this disease. At present, most patients suffering from open angle glaucoma have started medical therapy. The goal is to reduce the intraocular pressure to an individualized target pressure in an effort to delay the progression of damage to the optic nerve. Until a decade ago, topical beta-adrenergic antagonists, adrenergic agonists, miotics and oral carbonic anhydrase inhibitors comprised the common medications in use. In the past decade many new drugs have been introduced. These drugs exert less systemic side effects and are very effective in lowering the intraocular pressure and furthermore, are easier to comply with. These include: local carbonic anhydrase inhibitors, prostaglandin F2á analogues and á2 adrenergic selective agonists. Due to lack of consensus as to the initial medication of choice for the commencement of treatment, the traditional tendency to initiate treatment with a local beta adrenergic antagonist persists. This review attempts to familiarize the reader with the new arsenal of glaucoma medications.

Medical management of angle closure glaucoma.

Management of angle closure glaucoma requires an understanding of the underlying pathophysiologic mechanisms. Treatment is aimed at eliminating pupillary block and other causes of angle closure, re-opening the angle, and preventing further damage to the optic nerve by lowering intraocular pressure. Medical therapy plays an important role in the successful management of this condition. This article describes commonly used pharmacologic agents, as well as newer classes of drugs such as topical carbonic anhydrase inhibitors, prostaglandin analogues and selective alpha2- adrenergic agonists. Use of these drugs in several clinically distinct angle closure syndromes and modes of presentation are discussed.

Involvement of neuropeptides in the allergic nasal obstruction in guinea pigs.

The purposes of the present study were i) to determine whether neuropeptides induce the nasal obstruction in guinea pigs, and ii) to examine the possible involvement of neuropeptides in allergic nasal obstruction. The decrease in nasal cavity volume was determined by acoustic rhinometry as an index of nasal obstruction. In non-sensitized guinea pigs, substance P (SP), neurokinin A (NKA) and calcitonin gene-related peptide (CGRP) caused the nasal obstruction 10 to 30 min after their intranasal application. LY303870 (1 mg/kg), a tachykinin NK1-receptor antagonist; SR48968 (1 mg/kg), a tackykinin NK2-receptor antagonist; and CGRP(8-37) (50 nmol/kg), a CGRP1-receptor antagonist, administered intravenously before the intranasal application of the neuropeptides, inhibited the responses induced by SP, NKA and CGRP, respectively. In the guinea pigs sensitized with dinitrophenyl-coupled Ascaris suum allergenic extract, the intranasal antigen challenge caused nasal obstruction. The response was biphasic and consisted of the early phase response (EPR) and the late phase response (LPR), which developed 30 min and 6 h, respectively, after the antigen challenge. Intravenous administration of LY303870 (1 mg/kg) before the antigen challenge inhibited the EPR, while those of SR48968 (1 mg/kg) and CGRP(8-37) (50 nmol/kg) inhibited the LPR. The present results suggest that neuropeptides are involved in the allergic nasal obstruction.

Twenty-four hour intraocular pressure reduction with latanoprost compared with pilocarpine as third-line therapy in exfoliation glaucoma.

PURPOSE: To compare the 24 hour efficacy of latanoprost 0.005% given every evening with that of pilocarpine 4% given four times daily as third-line therapy in patients with exfoliation glaucoma receiving timolol 0.5% and dorzolamide 2% each given twice daily. METHOD: We enrolled 30 patients with exfoliation glaucoma not adequately controlled on timolol maleate 0.5% and dorzolamide 2%. Each patient underwent a baseline 24 hour intraocular pressure curve testing at 06:00, 10:00, 14:00, 18:00, 22:00 and 02:00 hours. Patients were randomised to receive either latanoprost 0.005% or pilocarpine 4% for a minimum of 8 weeks and were then crossed over to the opposite therapy. Diurnal curve testing was repeated at the end of each treatment. RESULTS: There was a significant decrease from baseline in intraocular pressure at each timepoint for both study medicines (p < 0.016). Latanoprost provided better intraocular pressure control than pilocarpine at daytime measuresments (17.4 vs 19.7 mmHg at 06:00 hours, p < 0.001; 17.8 vs 19.1 mmHg at 10:00 hours, p = 0.04). However, pilocarpine reduced the pressure more than latanoprost at 22:00 hours (18.4 vs 19.5 mmHg, p = 0.016). Overall, the diurnal intraocular pressure was reduced from a baseline of 21.5 +/- 3.7 mmHg to 18.8 +/- 3.1 mmHg on pilocarpine and to 18.0 +/- 3.0 mmHg on latanoprost (p = 0.06). In addition, mean peak pressure was similar between pilocarpine (21.0 +/- 2.9 mmHg) and latanoprost (20.5 +/- 3.8 mmHg) (p = 0.20). Side-effects were similar with the exception of blurred vision, which was only found with pilocarpine (10%). Compliance was more difficult with pilocarpine. CONCLUSION: In exfoliation glaucoma, as a third-line adjunctive therapy added to timolol and dorzolamide, latanoprost and pilocarpine have similar diurnal efficacy. However, latanoprost provides a greater morning pressure reduction.

Pharmaceutical management of the childhood glaucomas.

Glaucoma in childhood is a diverse, blinding group of conditions, which presents a major therapeutic challenge. Treatment is primarily surgical with medical treatments used as an adjunct. None of these drugs has been granted approval by the regulatory agencies for use in children, but they are used on a compassionate basis. Issues of efficacy and safety of these medications in children are discussed. beta-adrenoceptor blockers have been employed as first line pharmaceutical therapy for many years. Recently three new classes of drugs have been developed for use in glaucoma in adults. beta-blockers remain first line therapy if there are no contraindications such as asthma. Topical carbonic anhydrase inhibitors (CAI) appear to be less effective than beta-blockers, but seem safe systemically, although associated with local irritation. They are useful as an adjunct to beta-blockers or as first line therapy when beta-blockers are contraindicated. Prostaglandins have not proved as effective in childhood glaucoma as in adult glaucoma, although it works well in some patients with juvenile open angle glaucoma (JOAG) and others with aphakic glaucoma. alpha-adrenergic agonists, although effective at least in the short-term, have serious, potential systemic side effects, which demand close observation when used in neonates and young infants.

The dorzolamide/timolol combination versus timolol plus pilocarpine: patient preference and impact on daily life. United States Patient Preference Study Group. International Patient Preference Study Group.

PURPOSE: To compare the 2.0% dorzolamide/0.5% timolol fixed combination (COSOPT; Merck & Co., Whitehouse Station, NJ) to 0.5% timolol plus 2.0% pilocarpine given concomitantly, and to determine patient preference, tolerability, and impact on daily life in patients with elevated intraocular pressure (IOP). METHODS: Two multi-center, randomized, cross-over, observer masked studies were conducted, one in the United States (97 patients) and one in Europe (93 patients). The Comparison of Ophthalmic Medications for Tolerability questionnaire was used to assess patient preference and perception of side effects and activity limitations resulting from study medications. Intraocular pressure was measured before and 2 hours after the morning dose of study medication (hour 0 and hour 2). RESULTS: In both studies, among patients with a preference, the combination was preterred to timolol plus pilocarpine by a ratio of 4 to 1. The most commonly cited reason for this preference was side effects. Patients in both studies also reported that the combination interfered significantly less with daily life in terms of side effects and activity limitations. They also reported missing significantly fewer doses of study medication while taking the combination and being significantly more satisfied with it. The efficacy of these two treatments was not significantly different, based on IOP measurements at hour 0 and 2 hours after administration. Patients reported significantly more adverse events while receiving timolol plus pilocarpine in both studies, and in the U.S. study, significantly more patients discontinued therapy while receiving timolol plus pilocarpine than while receiving the combination. CONCLUSION: Compared with timolol plus pilocarpine, patients preferred the combination of 2% dorzolamide/0.5% timolol, and reported less interference in daily activities, better tolerability, and better compliance with therapy.

[Influence of postoperative topical application of miotics after cataract extraction on intraocular pressure and the blood-aqueous barrier]. / Unmittelbar postoperative Applikation von Miotika nach Katarakt-Extraktion. Einfluss auf Augeninnendruck un Blut-Kammerwasser-Schranke.

BACKGROUND: In the present study we evaluated the influence of topical miotics on intraocular pressure and the blood-aqueous barrier after uncomplicated phacoemulsification and PC-IOL implantation. PATIENTS AND METHODS: Fifty-two eyes were randomized into 2 groups: with miotics (n = 28) and without miotics (n = 24). The IOP was measured before, 6 h, 1 and 2 days after surgery. Measurement of aqueous flare was performed before and on days 1 and 2 after surgery. Patients with glaucoma, PEX or previous intraocular surgery were excluded. RESULTS: In the group without miotics the IOP was 17.9 mm Hg (+/- 3.34) 6 h postoperatively; in the second group it was 15.5 mm Hg (+/- 3.25); P = 0.04. On the first postoperative day the IOP measured in the group without miotics was 15.3 mm Hg (+/- 2.70) and with miotics 13.0 mm Hg (+/- 2. 28); P = 0.007. On the second day in the group without miotics the IOP was 13.9 mm Hg (+/- 3.05) and with miotics 12.60 mm Hg (+/- 2. 19); P = 0.53. The changes in aqueous flare on the first and second day after surgery showed no significant influence of miotics on the blood-aqueous barrier (P > 0.05). CONCLUSIONS: Immediate postoperative application of topical miotics led to a small yet significant reduction of the IOP during the first 24 h after surgery. Our data suggest that there is no need for pharmacological reduction of the IOP after uncomplicated cataract surgery.