Topiramate-associated acute, bilateral, angle-closure glaucoma: case report

This paper describes a topiramate induced acute bilateral angle-closure glaucoma. This rare adverse effect is an idiosyncratic reaction characterized by uveal effusion and lens forward displacement, leading to increased intraocular pressure and vision loss. We describe a 55 year-old white woman with migraine, spasmodic torticollis and essential tremor, who developed bilateral acute angle-closure glaucoma, one week after starting topiramate 25 mg/day. She was seen at the Ophthalmology Emergency Department of the Fundação João Penido Burnier (Campinas, SP, Brazil) with a 4 hours history of blurry vision, ocular pain and bright flashes vision. Slit lamp examination revealed moderate conjunctival injection and corneal edema, and shallow anterior chambers. Intraocular pressure was 48 mmHg in both eyes. Fundoscopic examination findings were normal. She was treated with timolol, brimonidine, dorzolamide, pilocarpine, prednisone acetate eye drops and acetazolamide. One hour after those measures, as the intraocular pressure was 30 mmHg, she received a manitol intravenous injection and the intraocular pressure normalized. After 24 hours an iridotomy with Yag laser was performed. Topiramate was discontinued and she was totally recovered after one week.

Blood-brain barrier disruption associated with topiramate-induced angle-closure glaucoma of acute onset.

BACKGROUND: Topiramate (Topamax(R)) is an anti-epileptic drug of the sulfamate group used secondarily for bipolar disease. HISTORY AND SIGNS: One week after initiation of topiramate treatment for a bipolar disorder, a 57-year-old man presented with blurred vision. Clinical examination revealed a bilateral conjunctivitis, areflexic mydriasis, severe anterior chamber shallowing, with a myopic shift and vitritis. THERAPY AND OUTCOME: A spinal tap revealed an increased protein content of 1581 mg/L on cerebrospinal fluid (CSF) analysis, being compatible with a rupture of the blood-brain barrier (BBB). UBM exposed bilateral ciliochoroidal effusions with secondary angle-closure. Topiramate was promptly discontinued, whereas visual acuity, intraocular pressure (IOP), and anterior and posterior segments anatomy normalized within 1 week. One month later, bilateral iris atrophy was present. CONCLUSION: The presence of BBB disruption with increased protein content in CSF with simultaneous blood ocular barrier breakdown may suggest a common inflammatory mechanism.

Argon-laser iridoplasty in the management of uveitis-induced acute angle-closure glaucoma.

PURPOSE: To report the use of argon laser iridoplasty in the management of uveitic acute angle-closure glaucoma. METHODS: Interventional case report. RESULTS: A 46-year-old man developed uveitic acute angle-closure glaucoma with an intraocular pressure (IOP) of 65 mmHg. After unsuccessful attempts with medical treatment and two laser peripheral iridotomies, iridoplasty allowed to break posterior synechiae, open the angle, and reduce the IOP within a few hours. CONCLUSIONS: Argon laser iridoplasty allowed rapid reduction of IOP and prevented the need for emergency surgery. Therefore, the authors stipulate that it is a viable management option in active uveitic acute angle-closure glaucoma.

The effectiveness of early lens extraction for the treatment of primary angle-closure glaucoma : a randomized controlled trial (EAGLE)

Medical Research Council (ref G0701604) and administered by the NIHR-EME (ref 09-800-26)

Effectiveness of early lens extraction for the treatment of primary angle-closure glaucoma (EAGLE): a randomised controlled trial

Background
Primary angle-closure glaucoma is a leading cause of irreversible blindness worldwide. In early-stage disease, intraocular pressure is raised without visual loss. Because the crystalline lens has a major mechanistic role, lens extraction might be a useful initial treatment.

Methods
From Jan 8, 2009, to Dec 28, 2011, we enrolled patients from 30 hospital eye services in five countries. Randomisation was done by a web-based application. Patients were assigned to undergo clear-lens extraction or receive standard care with laser peripheral iridotomy and topical medical treatment. Eligible patients were aged 50 years or older, did not have cataracts, and had newly diagnosed primary angle closure with intraocular pressure 30 mm Hg or greater or primary angle-closure glaucoma. The co-primary endpoints were patient-reported health status, intraocular pressure, and incremental cost-effectiveness ratio per quality-adjusted life-year gained 36 months after treatment. Analysis was by intention to treat. This study is registered, number ISRCTN44464607.

Findings
Of 419 participants enrolled, 155 had primary angle closure and 263 primary angle-closure glaucoma. 208 were assigned to clear-lens extraction and 211 to standard care, of whom 351 (84%) had complete data on health status and 366 (87%) on intraocular pressure. The mean health status score (0·87 [SD 0·12]), assessed with the European Quality of Life-5 Dimensions questionnaire, was 0·052 higher (95% CI 0·015–0·088, p=0·005) and mean intraocular pressure (16·6 [SD 3·5] mm Hg) 1·18 mm Hg lower (95% CI –1·99 to –0·38, p=0·004) after clear-lens extraction than after standard care. The incremental cost-effectiveness ratio was £14 284 for initial lens extraction versus standard care. Irreversible loss of vision occurred in one participant who underwent clear-lens extraction and three who received standard care. No patients had serious adverse events.

Interpretation
Clear-lens extraction showed greater efficacy and was more cost-effective than laser peripheral iridotomy, and should be considered as an option for first-line treatment.

Phacoemulsification Versus Peripheral Iridotomy in the Management of Chronic Primary Angle Closure: Long-Term Follow-Up

Primary angle closure occurs as a result of crowded anterior segment anatomy, causing appositional contact between the peripheral iris and trabecular meshwork, thereby obstructing aqueous outflow. Several studies highlight the role of the crystalline lens in its pathogenesis. The objective of this work is to compare the long-term efficacy of phacoemulsification versus laser peripheral iridotomy (LPI) in the management of chronic primary angle closure (CPAC). Prospective case-control study with 30 eyes of 30 patients randomly divided in two groups: 15 eyes in the LPI group and 15 eyes in the IOL group. Patients in the LPI group underwent LPI using argon and Nd:YAG laser. Patients in the IOL group underwent phacoemulsification with posterior chamber intraocular lens (IOL) implantation. Examinations before and after the procedure included gonioscopy, Goldmann applanation tonometry, and anterior chamber evaluation using the Pentacam rotating Scheimpflug camera. The mean follow-up time was 31.13 ± 4.97 months. There was a statistically significant reduction in the intraocular pressure (IOP) and number of anti-glaucoma medications (p < 0.01) only in the IOL group. Anterior chamber depth, angle, and volume were all higher in the IOL group (p < 0.01) at the end of the follow-up period. Phacoemulsification with posterior chamber IOL implantation results in a higher anterior chamber depth, angle, and volume, when compared to LPI. Consequently, phacoemulsification has greater efficacy in lowering IOP and preventing its long-term increase in patients with CPAC and cataract.

Avaliação dos tipos de glaucoma no serviço de oftalmologia da UNICAMP

PURPOSE: To evaluate the frequency of different types of glaucoma at the Hospital das Clínicas of Campinas State University. METHODS: Cross-sectional study of 329 patients followed at the Glaucoma Service of Campinas State University from October 1 to December 20, 2000. The frequency of each type of glaucoma and the treatment were analyzed. RESULTS: There were 329 patients examined at the Glaucoma Service: 132 (40.1%) were referred to the service as glaucoma suspects and 197 (59.9%) as glaucoma patients. Ninety of the 132 glaucoma suspects had glaucoma (68.2%) and 42 are still under investigation (31.8%). Among the 329 patients, 283 (86%) had glaucoma, 42 (12.8%) were glaucoma suspects, 2 (0.6%) had ocular hypertension and 2 (0.6%) did not have glaucoma. There were 530 eyes with glaucoma: 298 (56.2%) with primary open angle glaucoma, 108 (20.4%) with chronic angle closure glaucoma, 21 (4%) with glaucoma following cataract surgery, 19 (3.6%) congenital glaucoma and 16 (3%) with low-tension glaucoma. All patients received initial clinical treatment with IOP-lowering medication. After a mean follow up of 10.5 months, 89 (16.8%) underwent laser therapy: 72 (13.6%) iridotomy, 7 (1.3%) trabeculoplasty and 10 (1.9%) panphotocoagulation. A hundred and seventy nine (33%) eyes required surgical treatment. CONCLUSION: The most frequent types of glaucoma were primary open angle and angle closure glaucoma. Low tension glaucoma and glaucoma associated with exfoliation syndrome were uncommon in this population.

Free conjunctival autologous graft for bleb repair and bleb reduction after trabeculectomy and nonpenetrating filtering surgery.

PURPOSE: To describe methods and outcomes of excisional revision of a filtering bleb (bleb revision) using free conjunctival autologous graft either for bleb repair or for bleb reduction after trabeculectomy and deep sclerectomy with an implant. METHODS: Retrospective medical records were reviewed for a consecutive non-comparative case series comprising patients who underwent excisional revision of a filtering bleb between May 1998-January 2001. Excisional revision using free conjunctival autologous graft (bleb revision) was performed either for bleb repair, to treat early and late leaks and hypotony with maculopathy, or for bleb reduction, to improve ocular pain, discomfort, burning, foreign body sensation, tearing, and fluctuations of visual acuity. The revision consisted of bleb excision and free conjunctival autologous graft. The bleb histopathology was analyzed in patients who underwent bleb repair. RESULTS: Sixteen patients were included in the study, consisting of nine patients who had a trabeculectomy and seven patients who had a deep sclerectomy with an implant. Bleb revision was necessary in 14 patients due to leaking filtering bleb (bleb repair), and in 2 patients due to bleb dysesthesia (bleb reduction). After a follow-up of 15.1 +/- 8.4 months, the mean intraocular pressure (IOP) rose from 7.8 +/- 6.3 mm Hg to 14.3 +/- 6.5 mm Hg, and the visual acuity from 0.4 +/- 0.3 to 0.7 +/- 0.3, with a P value of 0.008 and 0.03, respectively. The complete success rate at 32 months, according to the Kaplan-Meier survival curve, was 38.3%, and the qualified success rate was 83.3%. Four patients (25%) required additional suturing for persistent bleb leak. To control IOP, antiglaucoma medical therapy was needed for six patients (37.5%) and repeated glaucoma surgery was needed for one patient. CONCLUSION: Free conjunctival autologous graft is a safe and successful procedure for bleb repair and bleb reduction. However, patients should be aware of the postoperative possibility of requiring medical or surgical intervention for IOP control after revision.

Four years later: a clinical update on latanoprost.

PURPOSE: Almost five years have elapsed since the introduction of latanoprost on several markets and considering the large number of publications dealing with it, the authors felt that it was worth re-evaluating the drug. METHODS: The criterion used to select trials for inclusion in the review was: all articles mentioning the drug in common electronic data-bases; these were then screened and considered, on the basis of methodological quality. RESULTS: Experimental data suggest that latanoprost acts by remodeling the extracellular matrix in the ciliary muscle, thus increasing the flow of aqueous humor through the ciliary muscle bundles of the uveoscleral pathway. POAG: Latanoprost persistently improves the pulsatile ocular blood flow in primary open angle glaucoma (POAG). Recent trials confirmed the greater IOP-lowering efficacy of latanoprost vs. timolol, dorzolamide, brimonidine and unoprostone. Trials lasting up to 24 months showed that latanoprost is effective in long-term treatment of POAG and ocular hypertension (OH), with no signs of loss of efficacy when compared to timolol or dorzolamide. Latanoprost provides better control of circadian IOP. Non-responders to beta-blockers should preferably be switched to latanoprost monotherapy before a combination therapy is started. The possibility of a fixed combination of latanoprost and timolol has been explored, with promising results. NTG: Latanoprost is effective in normal tension glaucoma (NTG), lowering IOP, improving pulsatile ocular blood flow and increasing ocular perfusion pressure. OTHER GLAUCOMAS: Latanoprost may provide effective IOP control in angle-closure glaucoma after iridectomy, in pigmentary glaucoma, glaucoma after cataract extraction and steroid-induced glaucoma. However, latanoprost was effective in only a minority of pediatric cases of glaucoma and is contraindicated in all forms of uveitic glaucoma. SAFETY: In the articles reviewed, new or duration-related adverse events were reported.

Comparison of techniques for measuring anterior chamber depth:Orbscan imaging, Smith's technique, and van Herick's method

Background Evaluation of anterior chamber depth (ACD) can potentially identify those patients at risk of angle-closure glaucoma. We aimed to: compare van Herick’s limbal chamber depth (LCDvh) grades with LCDorb grades calculated from the Orbscan anterior chamber angle values; determine Smith’s technique ACD and compare to Orbscan ACD; and calculate a constant for Smith’s technique using Orbscan ACD. Methods Eighty participants free from eye disease underwent LCDvh grading, Smith’s technique ACD, and Orbscan anterior chamber angle and ACD measurement. Results LCDvh overestimated grades by a mean of 0.25 (coefficient of repeatability [CR] 1.59) compared to LCDorb. Smith’s technique (constant 1.40 and 1.31) overestimated ACD by a mean of 0.33 mm (CR 0.82) and 0.12 mm (CR 0.79) respectively, compared to Orbscan. Using linear regression, we determined a constant of 1.22 for Smith’s slit-length method. Conclusions Smith’s technique (constant 1.31) provided an ACD that is closer to that found with Orbscan compared to a constant of 1.40 or LCDvh. Our findings also suggest that Smith’s technique would produce values closer to that obtained with Orbscan by using a constant of 1.22.

Assessing the Glaucoma Quality of Life-15 (GCL-15) Questionnaire, Goldmann Tonometry and Moorfields Motion Displacement Test in Glaucoma Case Finding

Purpose: To compare the performance Glaucoma Quality of Life-15 (GQL-15) Questionnaire, intraocular pressure measurement (IOP Goldmann tonometry) and a measure of visual field loss using Moorfields Motion Displacement Test (MDT) in detecting glaucomatous eyes from a self referred population. Methods: The GQL-15 has been suggested to correlate with visual disability and psychophysical measures of visual function in glaucoma patients. The Moorfields MDT is a multi location perimetry test with 32 white line stimuli presented on a grey background on a standard laptop computer. Each stimulus is displaced between computer frames to give the illusion of "apparent motion". Participants (N=312, 90% older than 45 years; 20.5% family history of glaucoma) self referred to an advertised World Glaucoma Day (March 2009) Jules Gonin Eye Hospital, Lausanne Switzerland. Participants underwent a clinical exam (IOP, slit lamp, angle and disc examination by a general ophthalmologist), 90% completed a GQL-15 questionnaire and over 50% completed a MDT test in both eyes. Those who were classified as abnormal on one or more of the following (IOP >21 mmHg/ GQL-15 score >20/ MDT score >2/ clinical exam) underwent a follow up clinical examination by a glaucoma specialist including imaging and threshold perimetry. After the second examination subjects were classified as "healthy"(H), "glaucoma suspect" (GS) (ocular hypertension and/or suspicious disc, angle closure with SD) or "glaucomatous" (G). Results: One hundred and ten subjects completed all 4 initial examinations; of these 69 were referred to complete the 2nd examination and were classified as; 8 G, 24 GS, and 37 H. MDT detected 7/8 G, and 7/24 GS, with false referral rate of 3.8%. IOP detected 2/8 G and 8/24 GS, with false referral rate of 8.9%. GQL-15 detected 4/8 G, 16/24 GS with a false referral rate of 42%. Conclusions: In this sample of participants attending a self referral glaucoma detection event, the MDT performed significantly better than the GQL-15 and IOP in discriminating glaucomatous patients from healthy subjects. Further studies are required to assess the potential of the MDT as a glaucoma screening tool.

Cirurgia de catarata e glaucoma

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Disturbed Correlation Between Arterial Resistance and Pulsatility in Glaucoma Patients

PURPOSE: (i) To investigate whether pulsatility index (PI) and mean flow velocities (MFV) are altered in glaucoma patients. (ii) To evaluate the significance of PI in retrobulbar autoregulation capacity. METHODS: Patients with primary open-angle glaucoma (POAG; n = 49), normal tension glaucoma (NTG; n = 62) and healthy controls (n = 48) underwent colour Doppler imaging measurements of the retrobulbar vasculature. Kruskal-Wallis test was used to compare variables between the three diagnostic groups. Restricted cubic splines were used to determine nonlinearities between the resistive index (RI) and PI correlations. RESULTS: Mean flow velocities (MFV) were lower in both short posterior ciliary arteries (SCPA) and central retinal arteries (CRA) from the two glaucoma groups (p < 0.04 versus healthy controls). No differences were detected in RI or PI in any arteries of the three diagnostic groups (p > 0.08). In healthy individuals, correlations between RI and PI were linear in all arteries. In both POAG and NTG patients, CRA presented a nonlinear curve with a cutpoint at RI 0.77 (p < 0.001) and 0.61 (p = 0.03), respectively, above which the slope increased nearly five- and tenfold (POAG: 1.96 to 10.06; NTG: -0.46-4.06), respectively. A nonlinear correlation in the ophthalmic artery was only observed in NTG patients, with a cutpoint at RI 0.82 (p < 0.001), above which the slope increased from 3.47 to 14.03. CONCLUSIONS: Glaucoma patients do not present the linear relationships between RI and PI observed in healthy individuals. Their nonlinear relations may be indicative of an altered autoregulation and suggest a possible threshold RI could be determined above which autoregulatory disturbances become more relevant.

In vivo testing of a novel adjustable glaucoma drainage device.

PURPOSE: We report on the in vivo testing of a novel noninvasively adjustable glaucoma drainage device (AGDD), which features an adjustable outflow resistance, and assess the safety and efficiency of this implant. METHODS: Under general anesthesia, the AGDD was implanted on seven white New Zealand rabbits for a duration of 4 months under a scleral flap in a way analogous to the Ex-PRESS device and set in an operationally closed position. The IOP was measured on a regular basis on the operated and control eyes using a rebound tonometer. Once a month the AGDD was adjusted noninvasively from its fully closed to its fully open position and the resulting pressure drop was measured. The contralateral eye was not operated and served as control. After euthanization, the eyes were collected for histology evaluation. RESULTS: The mean preoperative IOP was 11.1 ± 2.4 mm Hg. The IOP was significantly lower for the operated eye (6.8 ± 2 mm Hg) compared to the nonoperated eye (13.1 ± 1.6 mm Hg) during the first 8 days after surgery. When opening the AGDD from its fully closed to fully open position, the IOP dropped significantly from 11.2 ± 2.9 to 4.8 ± 0.9 mm Hg (P < 0.05). CONCLUSIONS: Implanting the AGDD is a safe and uncomplicated surgical procedure. The fluidic resistance was noninvasively adjustable during the postoperative period with the AGDD between its fully closed and fully open positions.