A phase II-III trial of olesoxime in subjects with amyotrophic lateral sclerosis.

BACKGROUND AND PURPOSE: To assess the efficacy and safety of olesoxime, a molecule with neuroprotective properties, in patients with amyotrophic lateral sclerosis (ALS) treated with riluzole. METHODS: A double-blind, randomized, placebo-controlled, multicenter trial of 18 months' duration was conducted in 512 subjects, with probable or definite ALS and a slow vital capacity (SVC) ≥70%, receiving 330 mg olesoxime daily or matching placebo and 50 mg riluzole twice a day in all. The primary intention-to-treat (ITT) outcome analysis was 18 months' survival. Secondary outcomes were rates of deterioration of the revised ALS functional rating scale (ALSFRS-R), focusing on the 9-month assessment, SVC and manual muscle testing. Blood levels, safety and tolerability of olesoxime were also assessed. RESULTS: At 18 months, 154 of the 512 ITT patients had died (79 of 253 placebo, 75 of 259 olesoxime). Estimated overall survival according to Kaplan-Meier analysis was 67.5% (95% CI 61.0%-73.1%) in the placebo group and 69.4% (95% CI 63.0%-74.9%) in the olesoxime group; hence survival was not significantly different between treatment arms (P = 0.71, stratified bulbar/spinal log-rank). The other efficacy end-points evaluated were also negative, with the exception of a small difference in ALSFRS-R global score at 9 months in favor of olesoxime but not sustained after 18 months' treatment nor evident in either the stratified bulbar or spinal subpopulations. Treatment did not raise any safety concerns. CONCLUSIONS: Olesoxime, although well tolerated, did not show a significant beneficial effect in ALS patients treated with riluzole.

Effects of varying 5-fluorouracil exposure duration on tenon's capsule fibroblasts.

PURPOSE: 5-Fluorouracil (5-FU) is used intraoperatively to improve the success of trabeculectomy Common practice is a 5-min application of 5-FU delivered via a Weck Cel sponge. The aim of this study was to determine if shorter exposure times were as effective in inhibiting Tenon's capsule fibroblast proliferation. METHODS: Samples of Tenon's capsules, obtained from young patients undergoing strabismus surgery, were immersed In vitro in 5-FU (50 mg/mL) for periods ranging from 1 to 10 min. Control samples were exposed either to growth medium (M 199) or 5-FU vehicle alone. Explants were cultured for up to 7 days and analysed for cell density, cell viability using fluoroprobe detection, and cell proliferation determined by proliferating cell nuclear antigen (PCNA)-staining. RESULTS: Exposure to 5-FU for 1 and 5 min resulted in a similar and significant inhibition of the culture-induced increase in stromal cell density (P < 0.01), a significant reduction in the percentage of viable cells (P < 0.02), and reduced PCNA indices, compared with controls. Exposure times of 3 and 10 min produced similar results. CONCLUSIONS: In vitro, under conditions of organ culture, a 1-min exposure to 5-FU had a significant antiproliferative effect on fibroblasts of Tenon's capsule, and was similar to 5 min of exposure. Optimal intraoperative 5-FU exposure time may be as little as 1 minute.

Beta radiation as an adjunct to low-risk trabeculectomy.

PURPOSE: To assess a single dose of intraoperative beta radiation used to enhance the success rate of trabeculectomy in a population of low-risk glaucoma patients in whom antimetabolites might not be indicated. METHODS: A prospective randomized trial of 65 eyes was designed, with 31 eyes receiving 750 rads of intraoperative beta radiation (group 1), and 34 eyes receiving no supplementation (group 2). RESULTS: Mean follow-up time was 24 months. Mean postoperative intraocular pressure was 12.2 mmHg in group 1, and 13.7 mmHg in group 2 (P = 0.16). Mean decrease in intraocular pressure was 10.3 mmHg in group 1, and 9.3 mmHg in group 2 (P = 0.49). The two groups were not significantly different in terms of surgical complications. CONCLUSION: For this population of low-risk patients, there was no significant difference in outcome after applications of a single intraoperative dose of beta radiation.

Intraoperative sponge 5-fluorouracil to reduce postoperative scarring in strabismus surgery.

INTRODUCTION: To determine whether 5-fluorouracil is effective in reducing scarring after strabismus surgery we used rectus muscle surgery in experimental animals to compare a single intraoperative dose of 5-fluorouracil with mitomycin C and to compare results in similarly treated controls not receiving these antimetabolites. METHODS: Muscle resections were performed on eight rabbits (16 eyes). Four eyes had 5-fluorouracil (50 mg/ml), and four eyes received mitomycin C (0.2 mg/ml), each of which was applied during surgery on an ophthalmic sponge for 5 minutes. Eight eyes served as controls. Six weeks after surgery conjunctival vascularity, muscle length-tension curves, muscle disinsertion force, and the histologic degree of scarring were assessed. RESULTS: The mitomycin C-treated eyes clearly had more conjunctival avascularity and a lower disinsertion force. Both treated groups had flatter length-tension curves and less scarring on histologic examination than the control eyes. CONCLUSIONS: Antifibroproliferative therapy with intraoperative sponge 5-fluorouracil appears as effective as, and is possibly safer than, mitomycin C. It may be a useful adjunct in recurrent strabismus surgery or in other situations where a risk of excessive postoperative scarring exists.

Endoscopic diode laser cyclophotocoagulation with a limbal approach.

BACKGROUND AND OBJECTIVE: Endoscopic diode laser cyclophotocoagulation with a limbal approach was reviewed retrospectively. The delivery system and procedure used as well as the role of this procedure in the management of glaucoma are discussed. PATIENTS AND METHODS: An 810-nm pulsed continuous-wave diode laser capable of 1.2-W output was used. The maximum treatment area is 7 to 8 clock hours with a single limbal incision. Generally, 800 mW were used for less than 1 second, for a total of 0.8 J per treatment. RESULTS: Eight eyes of 6 patients were treated. The mean follow-up time for each procedure was 3.2 months (range 1 to 8 months) and for each eye was 5.1 months (range 2 to 8 months). Pre- and postoperative intraocular pressures were determined. Postoperative inflammation was the most common complication. CONCLUSION: One reason for the failure of transscleral cyclophotocoagulation, particularly in congenital glaucoma, may be displacement of the ciliary processes. This displacement does not permit the indirect treatment to reach the appropriate area. Because endoscopic laser cyclophotocoagulation allows direct visualization, treatment can be accurately applied to individual ciliary processes.

Risk of microbial contamination with multiple use of 5-fluorouracil vials.

PURPOSE: To determine whether microorganisms are able to survive in a solution of 50 mg/ml of 5-fluorouracil (5-FU) and, therefore, whether there is a risk of vial contamination with multiple use. METHODS: Ten common nosocomial pathogens were tested. Minimal inhibitory concentrations (MICs) of 5-FU were determined for each organism. Organisms were then inoculated into 1 ml of 5-FU (50 mg/ml) and, after timed periods of exposure, were plated onto blood agar and incubated at 37 degrees C. Plates were checked daily for the presence or absence of growth. RESULTS: The MICs of Klebsiella pneumoniae and Pseudomonas cepacia were within one log unit of the 10 mg/ml concentration of 5-FU used by some clinics. After incubation in 5-FU for 1 h, all species survived; after 24 h of exposure, five of the 10 species-Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, K. pneumoniae, and Proteus mirabilis-were still viable. CONCLUSION: 5-FU has limited bactericidal activity, and there is a risk of contamination if 5-FU vials are used in multiple dose fashion.

Update on the subconjunctival THC:YAG (holmium) laser sclerostomy Ab externo clinical trial: a 4-year report.

BACKGROUND AND OBJECTIVE: This is a follow-up report on 103 THC:YAG (holmium) sclerostomies ab externo performed on 87 eyes of 81 patients. PATIENTS AND METHODS: The patients received pulse energies of 0.06 to 0.13 J (mean total energy 4.4 +/- 3.3 J, range 0.6 to 17.1 J). RESULTS: The estimated success rates with or without medication, and allowing a second procedure, were 44% at 2 years and 36% at 4 years. The mean preoperative intraocular pressure (IOP) was 29.7 +/- 11.4 mm Hg, and the mean postoperative IOP in the successful patients was 13.6 +/- 4.6 mm Hg (P < .01). Hypotony and iris incarceration were the most frequent early complications. CONCLUSIONS: Although holmium laser sclerostomy is a relatively straightforward procedure and offers some advantages over standard trabeculectomy in select cases, it currently has a number of drawbacks that limit its use.

A high prevalence of occludable angles in a Vietnamese population.

PURPOSE: To assess the prevalence of occludable angles in a Vietnamese population. METHODS: The authors retrospectively reviewed the angle status in 482 Vietnamese patients who presented to a general ophthalmology practice. All angles were graded by a glaucoma specialist according to the Shaffer method. Patients were excluded if they had known glaucoma or narrow angles, or a history of trauma or intraocular surgery. RESULTS: A total of 29.5% of all patients surveyed and 47.8% of those 55 years of age or older had grade 0 to 2 angles. In the Framingham study, 3.8% of white patients 55 years of age or older had grade 0 to 2 angles. Of the patients in our study population, 8.5% had grade 0 to 1 angles and were considered at high risk for occlusion. CONCLUSIONS: Vietnamese patients have a much higher prevalence of narrow angles and a greater risk of angle-closure glaucoma than white patients.

Trabeculectomy with intraoperative sponge 5-fluorouracil.

PURPOSE: To retrospectively assess the outcome of trabeculectomy surgery performed using intraoperative sponge 5-fluorouracil (5-FU) (50 mg/ml). METHODS: Trabeculectomy with intraoperative sponge 5-FU was performed on 140 eyes of 119 patients. The reduction in intraocular pressure (IOP), the number of supplementary postoperative injections, and any treatment complications were noted. RESULTS: The mean preoperative IOP was 25.7 +/- 8.6 mmHg. The mean postoperative IOP was 12.5 +/- 5.7 mmHg with a mean IOP reduction of 52 percent (P < 0.0001). One hundred twenty-one (86.4 percent) eyes required no postoperative glaucoma medications, with the mean number of glaucoma medications dropping from 2.5 +/- 1.1 before operation to 0.3 +/- 0.8 after operation (P < 0.001). One hundred five eyes received a mean of 5.3 +/- 2.7 postoperative 5-FU injections. There was no significant difference in final IOP or success rate between low- and high-risk eyes, but high-risk eyes seemed to require supplementary postoperative 5-FU. Corneal epithelial damage arose in 52 (37 percent) eyes and correlated strongly with postoperative 5-FU supplementation. CONCLUSION: Intraoperative sponge 5-FU is a reasonably safe and effective adjunct to trabeculectomy surgery.

Surgical treatment of superior oblique palsy.

Reports of several large series of patients with superior oblique palsy (SOP) published in 1986 or before set forth important guidelines for both diagnosis and treatment of this condition. Newer information about the anatomy, physiology, and pathophysiology of the superior oblique has accrued over the past decade. This paper reviews our experience with diagnosis and treatment of SOP over the past 5 years in light of this new information. Charts of patients treated for SOP over 5 year (1990 to 1995) were reviewed for male or female sex, age, symptoms, refraction, vision, stereo acuity, head posture, facial asymmetry, intraoperative superior oblique traction test, diagnostic position prism and cover test, torsion, surgery performed, and results of treatment. The charts of 190 patients were reviewed. In 181, postoperative examinations were performed by us. The etiology of the SOP was congenital in 137 and acquired in 53. Twenty-nine acquired cases were due to trauma and 24 arose from other causes. Fifty-six patients had facial asymmetry, 51 of whom had congenital SOP. Ninety-five had a lax tendon, 83 (87%) of whom had congenital SOP. Sixty-six had a normal tendon, 29 (44%) of whom had acquired SOP. Seventy-seven percent of patients had Knapp class I, III, or IV palsy. An average of 1.26 surgeries was performed per patient. Inferior oblique weakening was performed in 177 (93%), while 68 vertical rectus recessions were done. Thirty-five patients had superior oblique tuck or resection, all on lax tendons, and 15 had Harada Ito procedures for torsion. Six patients had mild Brown syndrome postoperatively, none of which required a takedown. A cure, defined as relief of symptoms or elimination of strabismus and head tilt, was achieved in 166 of 181 (92%) of patients. Successful treatment of SOP can be accomplished in the majority of cases by selective surgery usually beginning with inferior oblique weakening plus additional vertical rectus and horizontal surgery as needed, with superior oblique strengthening used only for lax tendons or when torsion is the main problem.

Long-term results of noncontact transscleral neodymium:YAG cyclophotocoagulation.

PURPOSE: To determine the long-term efficacy of noncontact transscleral neodymium:YAG (Nd: YAG) cyclophotocoagulation. METHODS: A retrospective analysis was made of 167 patients (173 eyes) with intractable glaucoma treated with noncontact Nd:YAG cyclophotocoagulation between December 1987 and November 1993, reviewing the treatment parameters, complications, and pre- and posttreatment intraocular pressure (IOP). The IOP was compared using a Student's t test, and the results were subjected to a Kaplan-Meier life-table analysis. Success was defined as an IOP of 22 mmHg or lower in the absence of phthisis and without having undergone any additional surgical procedures. RESULTS: Mean follow-up was 30.5 +/- 22.8 months. Mean preoperative IOP was 40.0 +/- 12.9 mmHg. Mean postoperative IOP was 19.8 +/- 11.4 mmHg (P < 0.05). The mean number of treatment sessions was 1.8 +/- 1.3 (range, 1-8) with 95 eyes (55%) having only one treatment. Kaplan-Meier survival analysis showed a probability of continued success at 3 years of approximately 73% and at 5 years of 45%. Complications included loss of two or more lines of Snellen visual acuity or one or more categories in the low-vision range (40%), phthisis (6.9%), epithelial defects (1.9%), and hyphema (0.6%). CONCLUSION: This study suggests that Nd:YAG transscleral cyclophotocoagulation provides a useful long-term reduction of IOP in eyes with advanced or complicated glaucoma, but there is a significant risk of visual loss associated with the procedure.

Continuous muscle fiber activity, peripheral neuropathy, and thymoma.

Two patients, one of them with myasthenia gravis, presented symptoms of continuous muscle fiber activity syndrome before discovery of a thymoma. Peripheral neuropathy was present in both patients, with axonal and demyelinating lesions in sural nerve biopsy. The syndrome remained unchanged or worse after thymectomy. Both patients died of associated complications.

Intrathecal administration of natural human interferon alpha in amyotrophic lateral sclerosis.

Ten patients with amyotrophic lateral sclerosis were given intrathecal injections of natural interferon alpha, 1 million units weekly for 7 to 24 weeks. Six patients completed the trial. Four voluntarily withdrew after 7 to 13 injections. The slopes of deterioration for 40 quantitative tests of neuromuscular function for the control and treatment periods were compared by paired t test in the six patients who completed the trial and in the patient who withdrew after 13 injections. No significant differences were found. The patients tolerated treatment well. The CSF reaction was modest and spontaneously reversible. Indomethacin and ibuprofen blocked interferon side effects.

Familial amyloidosis with cranial neuropathy and corneal lattice dystrophy.

A 64-year-old woman had bilateral facial weakness, mild peripheral neuropathy, incoordination, and impaired balance. A corneal transplant had been performed for corneal lattice dystrophy. Sural nerve biopsy showed mild axonal neuropathy with deposits of amyloid in the perineurium. Histochemical studies showed amyloid protein AA in the nerve, but not in cornea or muscle.

Bovine brain gangliosides in the treatment of human sensory and motor neuronal degenerations.

Report of an open trial on the effect of bovine brain gangliosides on patients with sensorimotor neuronal degeneration. The results were encouraging and stress the need for well controlled trials.

A double-blind controlled trial of bovine brain gangliosides in amyotrophic lateral sclerosis.

We conducted a double-blind controlled study of the effect of brain gangliosides in amyotrophic lateral sclerosis. Nineteen patients received intramuscular gangliosides (40 mg/d) for 6 months, and 21 received placebo. The deterioration rates for approximately 120 clinical and electrophysiologic parameters of neuromuscular function were analyzed, but no statistically significant beneficial effect of the drug was demonstrated. However, the large coefficient of variation for each item indicated that a sample size of several hundred patients would have been necessary to exclude the possibility that the drug produced a 25% slowing of progression of the disease.