Determinants of visual acuity outcomes in eyes with neovascular AMD treated with anti-VEGF agents: an instrumental variable analysis of the AURA study.

PurposeTo identify the strongest variable(s) linked with the number of ranibizumab injections and outcomes in AURA, and to identify ways to improve outcomes using this association.MethodsAURA was a large observational study that monitored visual acuity over a 2-year period in patients with neovascular age-related macular degeneration (AMD) who received ranibizumab injections. Baseline characteristics, resource use, and outcomes were analyzed using an instrumental variable approach and regression analysis.ResultsData were analyzed from 2227 patients enrolled in AURA. Optical coherence tomography (OCT) and ophthalmoscopy were the most common diagnostic tests used, and this combination was the strongest instrumental variable. Use of OCT and ophthalmoscopy affected the number of injections given and resulted in an increase in visual acuity gains from baseline of 17.6 letters in year 1 and 2.5 letters in year 2. Regression models using the instrumental variable (OCT and ophthalmoscopy combined) showed that ≥5.1 (95% CI: 3.3-11.4) ranibizumab injections were needed to maintain visual acuity from baseline to year 1 and ≥8.3 (95% CI: 5.3-18.8) injections were needed to maintain visual acuity from year 1 to year 2. To gain ≥15 letters, ≥7.9 (95% CI: 5.1-17.5) ranibizumab injections would be needed in year 1 and ≥16.1 (95% CI: 10.3-36.4) injections would be needed over 2 years.ConclusionsThese findings highlight the role that regular monitoring plays in guiding neovascular AMD therapy and they showed that the number of ranibizumab injections needed to maintain visual acuity is higher than that administered in AURA.

Low-dose, short-term oral prednisone in the treatment of carpal tunnel syndrome.

We evaluated the effectiveness of low-dose, short-term oral prednisone in ameliorating the pain and other symptoms of carpal tunnel syndrome (CTS) in a randomized, double-blind, placebo-controlled study of patients with mild to moderate CTS. Prednisone, in doses of 20 mg daily for the first week and 10 mg daily for the second week, resulted in significant improvement in global symptom scores. The effect was rapid, but gradually waned over 8 weeks of observation. This approach may provide a treatment alternative in the short-term, conservative management of CTS.

Early seizures following intracerebral hemorrhage: implications for therapy.

Seizures occurred in 19 of 112 patients (17%) with nontraumatic, supratentorial intracerebral hemorrhage (ICH). All seizures occurred at ICH onset; patients without seizures at hemorrhage onset remained seizure-free until the last recorded follow-up. Seizures were significantly associated with extension of blood into the cerebral cortex. We found no association between seizures and hemorrhage size or the presence of subarachnoid or intraventricular blood. These data suggest that (1) seizures, in ICH, occur at hemorrhage onset, (2) patients without seizures at hemorrhage onset are at very low risk for subsequent seizures during their hospitalization, (3) hemorrhage involving the cerebral cortex, regardless of site of origin, predisposes to seizures, and (4) the prophylactic use of anticonvulsants in the acute management of these patients appears unwarranted, especially in patients without cortical extension.

Dose response, coasting, and differential fiber vulnerability in human toxic neuropathy: a prospective study of pyridoxine neurotoxicity.

We administered either 1 or 3 g/d of pyridoxine (vitamin B6) to five healthy volunteers and repeatedly followed serum pyridoxal phosphate levels, clinical symptoms and signs, quantitative sensory thresholds (QSTs), and sural nerve electrophysiology. Pyridoxine was discontinued at the first sign of either clinical or laboratory abnormality. In all subjects, sensory symptoms and QST abnormalities occurred concurrently. Subjects receiving higher doses became symptomatic earlier than low-dose subjects. Elevation of thermal QSTs preceded or exceeded that for vibration in the three low-dose subjects; vibration and thermal QST became abnormal simultaneously in the higher-dose subjects. A reduction in the amplitude of the sural sensory potential lagged behind QST changes in two of three subjects. Symptoms continued to progress ("coasting") for 2 to 3 weeks despite stopping pyridoxine administration and the return of serum pyridoxal phosphate levels to normal. This study suggests that (1) there is a clear dose-percent relationship for pyridoxine-induced neuropathy, (2) QST is a sensitive measurement for detecting early peripheral neuropathy; QST abnormalities may precede changes in nerve conduction studies, (3) coasting appears unrelated to persistently elevated blood levels of the toxin, and (4) a dose-dependent vulnerability may exist among nerve fibers of different caliber when exposed to an axonal toxin, such as pyridoxine.

Cervical root stimulation in the diagnosis of radiculopathy.

Cervical root stimulation (CRS) was compared with conventional EMG, nerve conduction, and late response studies in 34 patients with possible cervical radiculopathy. Cervical roots were stimulated by monopolar needles inserted into paraspinal muscles, recording compound muscle action potentials in biceps, triceps, and abductor digiti minimi muscles. In 18 patients with clinical evidence of radiculopathy, EMG was abnormal in 11 (61%), but CRS was abnormal in all 18. Of 16 patients with symptoms but no signs of radiculopathy, EMG was abnormal in 5 (31%) and CRS was abnormal in 9 (56%).

Prevalence of peripheral neuropathy in injection drug users.

BACKGROUND: Nucleoside analogue reverse transcriptase inhibitors are a critical component of antiretroviral therapy in HIV-infected persons. Several of these medications cause painful, dose-limiting peripheral neuropathy (PN), which may develop earlier and more intensely in persons with preexisting neuropathy. The prevalence of baseline peripheral neuropathy in injection drug users (IDUs), one of the largest populations of HIV-infected persons, has not been described, yet has important implications for the selection of antiretroviral therapy. METHODS: The authors performed a cross-sectional study of PN in 212 HIV-seronegative and HIV-seropositive IDUs using detailed neurologic histories, physical examinations, quantitative electrophysiologic study, and quantitative sensory testing. Data were used to assign patients to one of four positive categories of PN or one of two negative categories. RESULTS: PN was present in 24.5% of HIV-seronegative IDUs, three to four times the reported frequency for HIV-seronegative persons in the general or male homosexual population. PN was present in 32.1% of HIV-seropositive patients. PN was axonal in nature and associated with increased age and alcohol use. PN was asymptomatic in 81% of HIV-seronegative and 71% of HIV-seropositive patients with PN. CONCLUSIONS: There is a high prevalence of PN in HIV-seronegative IDUs. Although these PNs do not seem to predispose HIV-seropositive IDUs to HIV-related PN, they may increase the likelihood of iatrogenic neuropathy. Intravenous drug users may need more diligent monitoring when administered nucleoside analogues than patients in risk groups with lower endemic rates of PN.

Lumbrical sparing in carpal tunnel syndrome: anatomic, physiologic, and diagnostic implications.

Motor axons supplying lumbrical muscles are less severely affected than axons supplying thenar muscles in the carpal tunnel syndrome; sometimes lumbrical motor fibers are less affected than digit 2 sensory fibers. This pattern is consistent with compression of both the anterior and posterior aspects of the median nerve in the carpal tunnel because nerve fibers responsible for thenar, lumbrical, and digit 2 functions lie in an anterior-posterior gradient within the distal median nerve. Recognition of lumbrical sparing supports the electrodiagnosis of carpal tunnel syndrome when the distal latency to thenar muscles or the palm-to-wrist mixed median nerve conduction velocity is normal.

2',3'-dideoxycytidine (ddC) toxic neuropathy: a study of 52 patients.

We administered the antiviral agent 2',3'-dideoxycytidine (ddC) to HIV-infected patients with either ARC or AIDS as part of the AIDS Clinical Treatment Group protocol 012 and serially evaluated them with neuropathic symptom questionnaires, neurologic examinations, nerve conduction studies, and quantitative sensory testing (QST). All patients treated with high-dose ddC (0.06 and 0.03 mg/kg every 4 hours) developed a painful, predominantly sensory peripheral neuropathy, with a mean onset of 7.7 weeks, which reached severe intensity over several days. Abnormalities of vibration QST threshold preceded clinical symptoms. Treatment with 0.01 mg/kg every 4 hours produced a similar neuropathy, although of milder severity, later onset (mean, 9.3 weeks), and slower progression. In these patients, the onset of clinical symptoms and QST abnormalities were coincident. Only two of six patients treated with 0.005 mg/kg every 4 hours developed clinical or laboratory evidence of neuropathy; in both cases it was very mild and delayed in onset (26 weeks). All patients treated with high-dose ddC reported progression of symptoms (coasting) for 2 to 3 weeks following discontinuation of therapy. This study documents a painful sensory neuropathy resulting from treatment with ddC. With high-dose treatment, only the rapidity of onset and progression differentiated it from the distal, predominantly sensory neuropathy of AIDS.

Pilot study of d-penicillamine, vitamins and minerals in multiple sclerosis.

A pilot study of the effect of D-penicillamine in multiple sclerosis (MS) was undertaken because of D-penicillamine's activity against RNA neurotropic viruses, because it is effective against the auto-immune disease, rheumatoid arthritis, and because both viruses and autoimmunity have been implicated in multiple sclerosis. We have treated 16 patients with advanced MS, nine on full doses (2-2.25 grams/day) and seven whose treatment was permanently stopped for reasons other than adverse reactions. There has been some improvement in most of those whose treatment was not withdrawn, and no change or deterioration in those not continued on the therapeutic regimen. Despite use of a high dosage regimen, such as has evoked intolerable side effects in a high percentage of patients with rheumatoid arthritis, we have experienced few side effects in a total of 48 patients suffering from diseases with auto-immune components, a finding we speculate is due to replacement of nutrients inactivated or removed by D-penicillamine, and to supplementation with selected nutrients.

Echocardiographic observations of paradoxic pulse without pericardial disease.

Echocardiograms were obtained in 10 normal patients and in 11 patients with respiratory insufficiency due to chronic obstructive lung disease (8) and to thoracic poliomyelitis (3). Only the eight patients with obstructive lung disease had paradoxic pulse. No patient had pericardial disease. The left ventricular internal dimension, stroke volume, and the mitral valve E-F slope and D-E excursion were measured. The inspiratory to expiratory ratio of each measurement was significantly lower in patients with obstructive lung disease than in normal subjects. The patients with thoracic poliomyelitis demonstrated almost no respiratory change in these measurements. The magnitude of the change in the measured factors probably relates to the degree of negativity of intrathoracic pressure during respiration. The inspiratory reduction of mitral valve motion and left ventricular internal dimension is not specific to tamponade but may be seen in patients who exhibit paradoxic pulse due to other conditions.

Endogenous Pseudallescheria boydii endophthalmitis. Clinicopathologic findings in two cases.

Two cases of endogenous Pseudallescheria boydii endophthalmitis are presented. One patient had severe pulmonary fibrosis but no history of ocular trauma and no clinical or laboratory evidence of immunocompromise. Despite therapy with repeated intravitreal miconazole nitrate injections and systemic fluconazole, enucleation of the globe was required, and the patient eventually died with disseminated pseudallescheriasis. The other patient was an immunosuppressed cardiac transplant recipient who also received systemic fluconazole therapy. The infected eye eventually required evisceration, but there was no evidence of disseminated pseudallescheriasis before his death of unrelated causes.

Lobar vs thalamic and basal ganglion hemorrhage: clinical and radiographic features.

One hundred and twelve patients with spontaneous supratentorial intracerebral hemorrhages were reviewed to identify features which distinguish lobar intracerebral hemorrhage (LH; n = 42) from thalamic or basal ganglionic hemorrhage (TGH; n = 70). Chronic hypertension occurred more commonly in TGH (TGH 67%; LH 48%) while bleeding diathesis was more common in LH (LH 19%; TGH 6%). Clinical presentations were extremely variable and not associated with the type of hemorrhage. Bleeding into the ventricles and hydrocephalus occurred more often with TGH. At last follow-up, there were minimal differences between LH and TGH in overall mortality and functional outcome of the survivors. Alertness on admission was associated with a good outcome regardless of the type of hemorrhage, while a low Glasgow Coma Scale score, coma, ataxic respiration, abnormal pupil reactions, acute hypertension, large hemorrhage size and intraventricular blood were associated with a poor outcome. These data confirm etiological distinctions between LH and TGH, but fail to confirm previously reported differences in clinical presentation and outcome.

Case report: echocardiographic observations in patients with Friedreich's ataxia.

Echocardiography was performed on 11 patients with Friedreich's Ataxia. Eight of 11 had asymmetric septal hypertrophy and systolic anterior motion of the anterior leaflet of the mitral valve at rest or after inhalation of amyl nitrite. Two patients had concentric left ventricular hypertrophy. In view of this high incidence of hypertrophic cardiomyopathy, echocardiography is suggested as part of the routine evaluation of the patient with Friedreich's Ataxia.

Visual outcome following penetrating globe injuries with retained intraocular foreign bodies.

BACKGROUND: In our institution the occurrence of endophthalmitis related to intraocular foreign bodies has been rare. In this review we analyse the outcome of eyes with retained intraocular foreign bodies presenting to two vitreoretinal surgeons over nearly 7 years. METHODS: Review of the records of 26 patients who presented to two surgeons in a tertiary care vitreoretinal service in Toronto between January 1989 and November 1995. Information documented included mechanism of injury, time from injury to definitive surgery, entry site, presence of vitreous hemorrhage, type of surgery performed, initial and final visual acuity, and development of endophthalmitis. RESULTS: All the injuries occurred in male patients, with a mean age of 36.1 (range 15 to 55) years. Most of the injuries occurred in the workplace, and in most cases (17 [65.4%]) the mechanism of injury was "metal on metal." The entry site was via a perforating wound of the cornea in 16 cases (61.5%). Almost all cases were repaired within 48 hours by means of pars plana vitrectomy. Concurrent lensectomy was required in 18 cases (69.2%) for lens damage at the time of the original injury. Vitreous hemorrhage was present in 22 cases (84.6%). One patient (3.8%) manifested clinically apparent endophthalmitis, which responded to intravitreal antibiotic therapy. Nineteen eyes (73.1%) had a final visual acuity of 6/24 or better. Eyes with coexisting or subsequent retinal detachment had significantly worse vision than those without retinal detachment (p < 0.001). INTERPRETATION: The incidence of endophthalmitis in our series is lower than that in other published series. Prompt definitive treatment was associated with a good prognosis in most cases.

Electrophysiologic correlates of weakness in L5/S1 radiculopathy.

INTRODUCTION: Management of patients with radiculopathy involves estimating the degree of physiologic and anatomic injury, and weighing that to predict the likely clinical course. OBJECTIVE: To determine whether low distal peroneal and tibial CMAP amplitudes correlate with weakness and fibrillations of functionally relevant muscles in L5/S1 radiculopathy (LSR). METHODS: We reviewed clinical and electrophysiologic data in 66 consecutive patients with LSR. RESULTS: A significantly greater number of patients with low peroneal CMAP amplitudes had weakness of L5 (p = 0.025) and S1 innervated leg muscles (p < 0.001). Low tibial CMAP amplitudes were also associated with weakness of S1 innervated muscles (p < 0.038). The association of low peroneal CMAP amplitudes with weakness persisted when weakness of at least 3 muscles was considered in the analysis for L5 (p < 0.0001) and S1 (p = 0.014) innervated muscles. CONCLUSIONS: Low peroneal and tibial CMAP amplitudes may serve as surrogate measures for segmental weakness of functionally relevant muscles in LSR.

Anterior chamber maintenance during drainage of a suprachoroidal hemorrhage in two phakic eyes.

BACKGROUND AND OBJECTIVES: The authors describe a technique for hemorrhage drainage following glaucoma surgery that uses an anterior chamber maintainer to minimize risk to the anterior lens capsule. PATIENTS AND METHODS: Two patients had suprachoroidal hemorrhages following filtration surgery. Because their eyes were phakic, an anterior chamber maintainer, as opposed to a 23-gauge butterfly needle, was used for aqueous replacement during hemorrhage drainage. RESULTS: The maintainer provided a stable anterior chamber environment during both drainage procedures. No damage to anterior chamber structures occurred, and the postoperative course was unremarkable in both patients. CONCLUSIONS: The use of a sharp-tipped infusion cannula may be contraindicated for the phakic patient who has a suprachoroidal hemorrhage. The anterior chamber maintainer is a useful alternative instrument in such cases.