Understanding and interpreting vision safety issues with vigabatrin therapy.

Vigabatrin is an irreversible inhibitor of γ-aminobutyric acid (GABA) transaminase. It is effective as adjunctive therapy for adult patients with refractory complex partial seizures (rCPS) who have inadequately responded to several alternative treatments and as monotherapy for children aged 1 month to 2 years with infantile spasms. The well-documented safety profile of vigabatrin includes risk of retinopathy characterized by irreversible, bilateral, concentric peripheral visual field constriction. Thus, monitoring of visual function to understand the occurrence and manage the potential consequences of peripheral visual field defects (pVFDs) is now required for all patients who receive vigabatrin. However, screening for pVFDs for patients with epilepsy was conducted only after the association between vigabatrin and pVFDs was established. We examined the potential association between pVFDs and epilepsy in vigabatrin-naïve patients and attempted to identify confounding factors (e.g., concomitant medications, method of vision assessment) to more accurately delineate the prevalence of pVFDs directly associated with vigabatrin. Results of a prospective cohort study as well as several case series and case reports suggest that bilateral visual field constriction is not restricted to patients exposed to vigabatrin but has also been detected, although much less frequently, in vigabatrin-naïve patients with epilepsy, including those who received treatment with other GABAergic antiepileptic therapy. We also reviewed published data suggesting an association between vigabatrin-associated retinal toxicity and taurine deficiency, as well as the potential role of taurine in the prevention of this retinopathy.

Primer on visual field testing, electroretinography, and other visual assessments for patients treated with vigabatrin.

Vigabatrin, an irreversible inhibitor of γ-aminobutyric acid transaminase, is an antiepileptic drug indicated in the United States as adjunctive therapy for adult patients with refractory complex partial seizures who have responded inadequately to several alternative treatments and for monotherapy treatment of infantile spasms in patients 1 month to 2 years of age. Approval of vigabatrin in the United States was contingent on the implementation of a Risk Evaluation and Mitigation Strategy (REMS) to manage the threat of a progressive, permanent bilateral concentric peripheral visual field defects (pVFDs) that may occur in patients treated with vigabatrin. The REMS is designed to promote compliance with evidence-based recommendations for baseline (within 4 weeks of the start of treatment) ophthalmologic evaluations and ongoing vision monitoring in all patients treated with vigabatrin. In view of the challenges associated with visual field testing in patients with epilepsy and in infants, clinicians must understand the qualitative (pattern of damage), quantitative (degree of damage), electrophysiologic, and adjunctive techniques recommended for monitoring vigabatrin-treated patients. The objectives of ongoing research are to characterize the onset, progression, and risk of developing vision loss during the first year of vigabatrin treatment and to evaluate the potential of noninvasive imaging as a method for monitoring retinal changes corresponding to the pVFD. This article provides an overview of visual field testing procedures and electroretinography, summarizes the clinical characteristics of vigabatrin-associated pVFDs, and provides recommendations for visual field and visual electrophysiology testing relevant to both adult and infant patients treated with vigabatrin.

Multifocal ERG in ethambutol associated visual loss.

AIM: To determine the anatomical site and extent of electrophysiological dysfunction in patients with ethambutol associated visual loss. METHODS: A comparative case series. Four patients with ethambutol associated visual loss underwent multifocal electroretinography (mERG). Two patients had advanced visual loss while two had early signs of toxicity. The N1-P1, N1, P1 amplitudes, N1, and P1 latencies were compared to 10 age and sex matched controls. RESULTS: mERG abnormalities were detected in the ethambutol treated patients. The N1 amplitude was significantly lower in the ethambutol treated patients than in the control group. CONCLUSION: Ethambutol is possibly toxic to the retina, and not only the optic nerve. The multifocal ERG may be of value to diagnose and monitor patients taking ethambutol.

Fractionated stereotactic radiotherapy for parasellar meningiomas: a preliminary report of visual outcomes.

BACKGROUND/AIM: Fractionated stereotactic radiotherapy (FSRT) is a new treatment for brain tumours that are close to critical structures, such as the visual apparatus. This study aims to assess the visual outcomes for patients with parasellar meningioma following FSRT. METHODS: A retrospective, non-comparative case series of 13 patients with parasellar meningiomas who were treated in one institution with FSRT between January 1995 and January 2001. RESULTS: 13 patients (26 eyes) were followed for a mean of 2 years. Visual acuity improved in four eyes (12.5%), remained stable in 18 eyes (75%), and worsened in three eyes (12.5%). Visual field improved in 15 eyes (57%), remained stable in six eyes (23%), and worsened in four eyes (15%). No adverse visual outcome occurred as a result of radiation. CONCLUSION: These preliminary findings suggest that FSRT is a safe and effective treatment for parasellar meningiomas.

Amiodarone induced optic neuropathy.

AIM: To determine the clinical features of amiodarone induced optic neuropathy, which may help distinguish it from non-arteritic anterior ischaemic optic neuropathy. METHODS: Retrospective observational case series of patients diagnosed with amiodarone induced optic neuropathy at the neuro-ophthalmology service from March 1998 to February 2001. Amiodarone was discontinued after discussion with the patient's cardiologist. Visual acuity, colour vision, automated perimetry, and funduscopy were performed on initial and follow up examinations. RESULTS: Three patients with amiodarone induced optic neuropathy presented with mildly decreased vision, visual field defects, and bilateral optic disc swelling. Upon discontinuing the medication, visual function and optic disc swelling slowly improved in all three patients. CONCLUSION: Amiodarone induced optic neuropathy can present with visual dysfunction, and is typically a bilateral process. Upon discontinuation of amiodarone, slow resolution of optic disc swelling occurs and visual function improves in some patients.

The prevalence of cupping in end-stage arteritic and nonarteritic anterior ischemic optic neuropathy.

OBJECTIVE: To evaluate the prevalence of cupping in arteritic anterior ischemic optic neuropathy (AAION) and nonarteritic anterior ischemic optic neuropathy (NAION). DESIGN: Retrospective, observational case series. PARTICIPANTS: Three hundred one patients. METHODS: Review of clinical records and color fundus photographs. MAIN OUTCOME MEASURES: Photographic and clinical interpretation of optic nerve appearance. RESULTS: Ninety-two patients with AAION and 102 with NAION were included in the study. Disc photographs of 42 patients (48%) with AAION and 32 patients (31%) with NAION were available for reassessment. These were presented in a masked fashion along with a random sample of 27 disc pairs considered to be 'normal' and 27 disc pairs with 'established glaucoma' according to two examiners. Cupping was present in 92% of eyes with AAION secondary to giant cell arteritis and in 2% of eyes with NAION (kappa = 0.96; P < 0.001). CONCLUSIONS: The end-stage optic disc appearance in AAION secondary to giant cell arteritis is cupping, whereas segmental or diffuse pallor without cupping is the typical disc appearance after NAION.

Intraocular pressure changes after treatment for Graves' orbitopathy.

OBJECTIVE: To evaluate the change in intraocular pressure (IOP) in subjects with Graves' orbitopathy (GO) after orbital decompression, strabismus surgery, and orbital radiation. DESIGN: Retrospective case review. METHODS: The charts of 172 consecutive subjects from the Neuro-ophthalmology Service at Wills Eye Hospital (Philadelphia, PA) with GO who underwent either orbital decompression, strabismus surgery, or orbital radiation between 1994 and 1999 were analyzed. Subject age, gender, diagnosis of glaucoma in either eye, use of systemic steroids or topical glaucoma medications, procedure performed, and the preoperative and postoperative IOP (in primary position and upgaze) were evaluated. RESULTS: Of 116 eyes that underwent orbital decompression, the mean preoperative IOP was 21.6+/-4.6 mmHg (standard deviation) in primary position and 27.9+/-6.8 mmHg in upgaze. The postoperative IOP was 17.5 mmHg +/- 3.0 mmHg in primary position and 20.1+/-4.7 mmHg in upgaze, a decrease in IOP of 18.9% in primary position and 27.9% in upgaze (P<0.001). Subjects taking glaucoma medication or who had IOP greater than 21 mmHg demonstrated a significantly (P<0.001) greater reduction in IOP postoperatively. The mean preoperative IOP in the 32 subjects who had strabismus surgery was 18.5+/-2.8 mmHg (primary position), and 24.7+/-4.3 mmHg (upgaze). Postoperative IOP was 16.1 mmHg (primary position) and 16.9 mmHg (upgaze), a decrease of 2.4 mmHg (13.3%, P<0.01 in primary position) and 7.8 mmHg (31.2%, P<0.01 in upgaze). There was no statistically significant reduction in IOP after orbital radiation. CONCLUSIONS: In the selected subgroup of subjects with GO who required intervention, orbital decompression and strabismus surgery resulted in a significant reduction in IOP in the early postoperative period, especially in subjects with preoperative IOP greater than 21 mmHg.

Gaze-evoked amaurosis produced by intraorbital buckshot pellet.

OBJECTIVE: To report the first case of gaze-evoked amaurosis secondary to an intraocular foreign body and to highlight the characteristic clinical findings of patients with this symptom. DESIGN: Case report and review of the literature. METHODS: Case review, clinical history, electrophysiologic testing, and follow-up. MAIN OUTCOME MEASURES: Visual acuity, automated perimetry, and visual fields. RESULTS: A case of gaze-evoked amaurosis as a result of an intraorbital foreign body is described, and 19 additional cases of gaze-evoked amaurosis are reviewed from the English language literature. These cases share certain characteristics including good vision in primary position with deterioration of vision in eccentric gaze; concurrent objective pupillary abnormalities in eccentric gaze; stereotypic onset and recovery of vision; and funduscopic abnormalities consisting of disc edema and chorioretinal folds. CONCLUSIONS: Gaze-evoked amaurosis is a reliable sign of intraconal mass lesion. We report the first case of gaze-evoked amaurosis secondary to an intraorbital foreign body.

The ice test versus the rest test in myasthenia gravis.

OBJECTIVE: To compare the ice test with the rest test in subjects with myasthenic and nonmyasthenic ptosis. DESIGN: Randomized, noninterventional trial. PARTICIPANTS: (1) Ten subjects with ptosis from previously undiagnosed myasthenia gravis. (2) Fifteen subjects with nonmyasthenic ptosis. METHODS: Application of ice compared with rest. MAIN OUTCOME MEASURES: Improvement in eyelid elevation in millimeters after the application of a surgical glove filled with ice or cotton. RESULTS: In myasthenic subjects, the median improvement of ptosis with the rest test was 2 mm and with the ice test was 4.5 mm. The difference between the rest and ice tests is significant (P: < 0.001). There was no improvement in ptosis in nonmyasthenic subjects with either test. CONCLUSION: In myasthenic ptosis, improvement in eyelid elevation after the ice test is in part caused by rest. The ice test significantly improves ptosis more than rest alone does.

Low diagnostic yield with second biopsies in suspected giant cell arteritis.

OBJECTIVES: The clinical diagnosis of giant cell arteritis may be confirmed with a biopsy of the superficial temporal artery. Because of "skip lesions," a histologic diagnosis of giant cell arteritis may be missed with a unilateral biopsy. The authors report a study that investigates whether a biopsy of the contralateral superficial temporal artery provides any additional information for confirmation of a diagnosis of giant cell arteritis. METHODS: Available medical records of 91 consecutive patients who underwent bilateral superficial temporal artery biopsy procedures were reviewed. Information that was abstracted included sequence of biopsy procedures, length specimens, and histologic diagnosis. Microslides from all biopsy specimens were retrieved and reexamined in a masked fashion by the ocular pathologist (RCE) who had made the original diagnoses. RESULTS: Seventy-two bilateral simultaneous superficial temporal artery biopsies and 19 bilateral sequential biopsies were performed. The mean length of biopsy specimens was 23 mm, and the mean length of the total artery removed from each patient was 33 mm. The pathologist's original diagnosis and the diagnosis at reexamination were in 100% agreement. In 90 (99%) of the 91 patients, the histologic diagnoses in the left and right superficial temporal arteries were the same. This is a concordance rate of 98.9% (38 of 39 positive biopsy results) among the positive biopsy results. CONCLUSION: There is a low yield of information from a second temporal artery biopsy in patients with suspected giant cell arteritis. This suggests that patients who present to the ophthalmologist with possible giant cell arteritis will, in most cases, have a similar diagnosis on both temporal artery biopsies if the specimens are adequate.

Not so slowly progressive visual loss.

A 51-year-old man presented with bilateral progressive visual loss during a 2-month period. Visual acuity was 20/60 in both eyes with bilateral constricted visual fields. Funduscopy revealed bilateral disk pallor and arteriolar attenuation. His vision declined rapidly during the next 2 weeks. Investigations showed a positive cerebrospinal fluid Venereal Disease Research Laboratory test (1:8). A diagnosis of neurosyphilis was made, and treatment was started with high-dose intravenous and intramuscular penicillin.

A color Doppler analysis of nifedipine-induced posterior ocular blood flow changes in open-angle glaucoma.

PURPOSE: This pilot study used color Doppler imaging to investigate the effects of nifedipine on the posterior ocular blood flow of patients with glaucoma progression at normal intraocular pressures. PATIENTS AND METHODS: Eighteen patients, 11 men and seven women with a median age of 61.7 years, were imaged before and 6 weeks after the initiation of 30 mg of sustained-release nifedipine (Procardia XL; produced by either Pfizer or Pratt) daily. RESULTS: There was no statistically significant change in the blood velocity of the ophthalmic artery, central retinal artery, and main nasal and temporal short posterior ciliary arteries after treatment with nifedipine. CONCLUSION: The routine use of nifedipine in patients with normal tension glaucoma progression is not supported by this study.