Severe Systemic Adverse Events Research Articles

Selective Ophthalmic Arterial Injection Therapy for Intraocular Retinoblastoma: The Long-Term Prognosis

To report the success rate, adverse events, and long-term prognosis of selective ophthalmic arterial injection (SOAI) therapy for intraocular retinoblastoma. Noncomparative case series. A total of 408 eyes of 343 patients. Retrospective chart review of patients with intraocular retinoblastoma treated with SOAI using a balloon catheter and melphalan between 1988 and 2007. The technical success rate of SOAI (we defined success as the successful injection of melphalan into the ophthalmic artery), ocular adverse events, systemic adverse events, secondary neoplasms, eye survival, and visual acuity. Selective ophthalmic arterial injection was successful in 1452 procedures of 1469 trials, and the success rate was 98.8%. Each eye received 1 to 18 rounds of SOAI. Two eyes (0.5%) developed severe orbital inflammation, and 2 eyes (0.5%) had diffuse chorioretinal atrophy. Transient periocular swelling or redness occurred in some cases. No severe systemic adverse events were detected. Transient bronchospasm occurred in 1 patient (0.3%), and transient vomiting occurred in several patients. Twelve secondary neoplasms occurred in 11 patients, and the cumulative incidence was 1.3% at 5 years, 4.8% at 10 years, and 5.8% at 15 years. The eye preservation rate was 100% in group A, 88% in group B, 65% in group C, 45% in group D, and 30% in group E according to the International Classification of Intraocular Retinoblastoma. Fifty-one percent of eyes had a visual acuity >0.5, and 36% of eyes had a visual acuity >1.0 at the last follow-up examination in cases without macular tumors. Selective ophthalmic arterial injection using a balloon catheter and melphalan achieved a success rate of 98.8% and was associated with few severe adverse events, including secondary neoplasms. More than half of the treated eyes were preserved, and more than half of the eyes without macular tumors maintained a visual acuity >0.5. Selective ophthalmic arterial injection is an established treatment method. We did not detect severe eye damage or severe systemic events; secondary neoplasms were seen but no more frequently than would otherwise have been expected. The author(s) have no proprietary or commercial interest in any materials discussed in this article.

The PEDVAC trial: Preliminary data from the first therapeutic DNA vaccination in HIV-infected children

The PEDVAC study is the first trial designed to analyze safety and immunogenicity of a therapeutic vaccination with a multiclade multigene HIV DNA vaccine (HIVIS) in infected children. Twenty HIV-1 vertically infected children (6–16 years of age), on stable antiretroviral treatment for at least 6 months with HIV-1 RNA < 50 copies/ml and stable CD4 counts (>400 cells/mm 3 or 25%) over 12 months of follow-up, were recruited into the study. Enrolled patients have been randomized into two arms: a control group of 10 children who continued previous antiretroviral treatment (HAART) (arm A) and a group of 10 children immunized intramuscularly with the HIVIS DNA vaccine in addition to previous HAART (arm B). Immunizations took place at week 0, 4, 12 and the boosting dose is planned at week 36. The 10 children in the vaccine group have received the first 3 priming doses of the HIVIS vaccine. Safety data showed good tolerance to the vaccination schedule. Mild cutaneous self-limeted reactions consisted of local irritation, usually itching or erythema +/− swelling at the injection site, were reported. No severe systemic adverse events have been observed. No vaccinated children had a decrease of CD4 T-cell counts from baseline. None experienced virological failure. Analysis of cellular immune responses was scheduled at week 0, 4, 12, 16, 20, 40, 60, 72 and 96 by standard lymphoproliferation assay, intracellular cytokine staining and cell-ELISA, a miniaturized assay to measure antigen-induced IFNγ secretion. Evaluation of these results is in progress and will provide key information on the status and changes of antigen specific immunity during HIV DNA immunization.

Efficacy of recombinant birch pollen vaccine for the treatment of birch-allergic rhinoconjunctivitis

Recombinant DNA technology has the potential to produce allergen-specific immunotherapy vaccines with defined composition. To evaluate the effectiveness of a new recombinant birch pollen allergen vaccine in patients with birch pollen allergy. A multicenter, randomized, double-blind, placebo-controlled trial was undertaken to compare the following 3 vaccines in 134 adults with birch pollen allergy: recombinant birch pollen allergen vaccine (rBet v 1a), licensed birch pollen extract, natural purified birch pollen allergen (nBet v 1), and placebo. Patients received 12 weekly injections followed by monthly injections of the maintenance dose containing 15 microg Bet v 1 for 2 years. Significant reductions (about 50%) in rhinoconjunctivitis symptoms (rBet v 1, P = .0002; nBet v 1, P = .0006; birch extract, P = .0024), rescue medication (rBet v 1, P = .0011; nBet v 1, P = .0025; birch extract, P = .0063), and skin sensitivities (P < .0001) were observed in the 3 actively treated groups compared with placebo during 2 consecutive pollen seasons. Clinical improvement was accompanied by marked increases in Bet v 1-specific IgG levels, which were higher in the rBet v 1-treated group than in the birch and nBet v 1-treated groups. New IgE specificities were induced in 3 of 29 patients treated with birch pollen extract, but in none of the 32 rBet v 1-treated or 29 nBet v 1-treated patients. No severe systemic adverse events were observed in the rBet v 1-treated group. The rBet v 1-based vaccine was safe and effective in treating birch pollen allergy, and induced a highly specific immune response.

Shall we use Avastin® or Lucentis® for ocular neovascularization?

Shall we use Avastin^® or Lucentis^® for ocular neovascularization?

Photodynamic Therapy for Subfoveal Choroidal Neovascularization Secondary to Age-related Macular Degeneration

To evaluate the safety and efficacy of verteporfin photodynamic therapy (PDT) in patients with subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). We retrospectively reviewed the chart records and fluorescein angiography of patients with subfoveal CNV who were treated with verteporfin PDT between September 2001 and March 2003 and who completed at least 1 year of follow-up. The primary efficacy outcomes were the proportions of patients whose Snellen visual acuities had more than 1 line increase, no change or more than 1 line decrease 1 year after study entry compared with their baseline examinations. The secondary efficacy outcome was the changes in the logarithm of the minimum angle of resolution visual acuities at 1-year follow-up. Complications were monitored and tabulated. Forty-eight eyes of 48 patients with subfoveal CNV secondary to AMD were enrolled in this study. The mean follow-up was 12.56 +/- 1.37 months. At their last visit, 10.4% of eyes had more than 1 line improvement in Snellen visual acuity, 72.9% of eyes had no change, and 16.7% experienced more than 1 line of visual acuity loss (7 eyes lost < 3 lines of Snellen visual acuity, 1 eye lost between 3 and 6 lines). None experienced more than 6 lines of visual loss. There was no statistically significant difference between baseline and final visual acuity for eyes with predominantly classic CNV, minimally classic CNV and occult without classic CNV (Wilcoxon Signed Rank test, p = 0.59 ). There was a positive correlation between baseline visual acuity and final visual outcome (Kruskal-Wallis test, p = 0.002). No severe systemic and ocular adverse events were encountered. Of our patients with subfoveal CNV secondary to AMD, 83.3% could maintain or improve their visual acuity 1 year after verteporfin PDT. The risk of deterioration in visual acuity due to subfoveal CNV could be reduced by verteporfin PDT. Baseline visual acuity is significantly correlated with the final proportion of visual outcome.

A preliminary comparison of the efficacy and tolerability of botulinum toxin serotypes A and B in the treatment of myofascial pain syndrome: A retrospective, open-label chart review

Background: Myofascial pain syndrome (MPS) is characterized by acute or chronic regional muscle pain associated with single or multiple trigger points within taut bands of muscle. Botulinum toxins have clinical utility when sustained focal muscle relaxation is required and may be a useful addition to the treatment armamentarium for MPS. Objective: The purpose of the present article was to compare the efficacy and tolerability of botulinum toxin serotypes A and B (BTX-A and BTX-B) in the treatment of MPS. Methods: This was a retrospective, open-label, single-center chart review. Charts of all patients who received either BTX-A or BTX-B for MPS between January and November 2001 were included in the review. Patients rated the intensity of their pain on a visual analog scale (VAS) from 0 = no pain to 10 = worst pain imaginable before and after receiving BTX-A or BTX-B. Results: The charts of 91 patients (74.7% female, 25.3% male; mean [SD] age, 47 [10.2] years) who received BTX-A (n = 56; mean dose, 256.9 U; range, 100–600 U) or BTX-B (n = 35; mean dose, 9000 U; range, 2500–20,000 U) were included in this retrospective review. Patients who received BTX-A had significantly greater mean reductions in VAS pain scores compared with those who received BTX-B (mean reduction, 2.7 vs 1.8, respectively; P < 0.001). Patients who received BTX-A also reported significantly longer durations of pain relief compared with those who received BTX-B (4.5 vs 2.7) months; P < 0.001). Eight of 56 patients (14.3%) in the group that received BTX-A reported mild adverse events that included flulike symptoms, injection-site pain, and weakness of the neck muscles. Seven of 35 patients (20.0%) in the group that received BTX-B reported adverse events that included mild flulike symptoms, dry eyes, severe visual disturbances, and severe dry mouth. Conclusion: Patients with MPS who received BTX-A reported significantly greater reductions in pain for longer durations compared with those who received BTX-B. No patients who received BTX-A experienced severe systemic adverse events, compared with 4 patients who received BTX-B. The results of this comparison are consistent with the US Food and Drug Administration-approved labeling indicating that BTX-A is not interchangeable with any other botulinum toxin in terms of biological activity.

Pharmacological profiles of the potent carbonic anhydrase inhibitor dorzolamide hydrochloride, a topical antiglaucoma agent

Carbonic anhydrase (CA) plays an important role in the secretion of aqueous humor. The orally administered CA inhibitor acetazolamide lowers the intraocular pressure (IOP) of patients with glaucoma. However, approximately 50% of patients stop treatment with acetazolamide as a consequence of intolerable side effects due to the extraocular inhibition of the enzyme. This prompted attempts to develop a topically active CA inhibitor. Merck Research Laboratories focused on developing a water- and solvent-soluble compound to penetrate the cornea. Dorzolamide hydrochloride is a potent inhibitor of human CA isoenzyme II, with an IC50 value of 0.18 nM in vitro. In contrast, its inhibitory activity against human CA isozyme I is much weaker (IC50 value of 600 nM). Topically administered dorzolamide penetrated the ciliary body, inhibited its CA activity and had a hypotensive effect in rabbits; in contrast, topical administration of acetazolamide or methazolamide did not decrease IOP. In clinical trials, dorzolamide administered 3 times daily was effective in lowering IOP in patients with open-angle glaucoma or ocular hypertension. The hypotensive effect of dorzolamide 0.5% was similar to that of oral CA inhibitors or timolol (0.25%) twice daily. Dorzolamide did not induce the severe systemic adverse events associated with oral CA inhibitors. Dorzolamide was as effective as pilocarpine or dipivefrine as an adjunctive therapy in patients receiving beta-adrenergic antagonists. Dorzolamide also reduced IOP and accelerated retinal arteriovenous passage time in addition to improving visual function in patients with normal-tension glaucoma.