Treatment Outcomes in Birdshot Chorioretinitis: Corticosteroid Sparing, Corticosteroid Discontinuation, Remission, and Relapse.

PURPOSE: To describe treatment-related outcomes among patients with birdshot chorioretinitis (BSCR). DESIGN: Retrospective cohort study. PARTICIPANTS: Patients diagnosed with BSCR at 2 tertiary care academic medical centers. METHODS: Clinical and treatment-related data were collected for all patients with BSCR diagnosed between 2003 and 2017 at the 2 centers and for each eye at each clinical visit. MAIN OUTCOME MEASURES: Four outcomes were considered: (1) corticosteroid-sparing success, defined as inactive disease and prednisone dose of ≤7.5 mg/day; (2) corticosteroid-discontinuation success, defined as inactive disease and discontinuation of prednisone; (3) sustained drug-free remission, defined as inactive disease off all medications for ≥3 months; and (4) relapse of BSCR after remission. RESULTS: A total of 107 patients with BSCR were identified, of whom 94 had follow-up data. Corticosteroid-sparing success was achieved in 95.4% of the oral corticosteroid-treated patients at a rate of 0.60 successes per person-year (PY) (95% CI: 0.50/PY, 0.70/PY). The median time to corticosteroid-sparing success was 12 months. Corticosteroids were discontinued successfully in 76.5% of oral corticosteroid-treated patients (rate = 0.28/PY; 95% CI: 0.21/PY, 0.35/PY). The median time to successful corticosteroid discontinuation was 2.0 years. A sustained drug-free remission was achieved in 24 patients (rate = 0.06/PY; 95% CI: 0.04/PY, 0.09/PY), with approximately 25% of patients achieving remission by 4 years of follow-up. Relapse of inflammation in patients after achieving a sustained, drug-free remission occurred at a rate of 0.24/PY (95% CI: 0.14/PY, 0.37/PY). CONCLUSIONS: Successful corticosteroid sparing and discontinuation was achieved in the majority of patients with BSCR. Remission occurred less often, but data were limited by the time needed to induce a remission (4 years) and the amount of follow-up (median, 4.6 years). The relapse rate after a remission was 0.24/PY.

IgG4-Related Ophthalmic Disease Presenting as Meningitis and Panuveitis.

PURPOSE: We report an uncommon case of immunoglobulin gamma 4-related ophthalmic disease (IgG4-ROD) presenting as meningitis and panuveitis. OBSERVATIONS: A 35-year-old male with no prior ophthalmic history presented with headaches, altered mental status, and fever of unknown origin. A lumbar puncture (LP) revealed an elevated white count with lymphocytic predominance, confirming a suspected meningitis. After an extensive work-up, he was discharged on oral acyclovir to cover for presumed aseptic meningitis. The patient initially improved, however, bilateral eye pain, redness, and photophobia 2 weeks after discharge prompted his first visit to the ophthalmology clinic. Exam at that time was consistent with bilateral anterior uveitis for which he was given topical prednisolone and cyclopentolate. In addition to the preceding work-up, quantitative immunoglobulin serology including IgG4 levels was added. At follow-up, he was found to have increased ocular inflammation with vitreitis, nerve head edema, and subclinical macular thickening. Visual acuity (VA) had decreased in both eyes. Serology titers for IgG had resulted in a significant elevation in IgG subclass 4 (IgG4). Optical coherence tomography (OCT) and fundus fluorescein angiography (FFA) confirmed posterior retinal involvement. The patient was diagnosed with presumed bilateral panuveitis secondary to IgG4-ROD. CONCLUSIONS AND IMPORTANCE: IgG4-RD can be a serious condition that requires careful consideration and intuition to diagnose. This report serves to encourage ophthalmologists to consider IgG4-ROD in cases of idiopathic systemic inflammation with ophthalmic involvement.

The Intercostal NMJ Assay: a new alternative to the conventional LD50 assay for the determination of the therapeutic potency of botulinum toxin preparations.

Therapeutic botulinum neurotoxin type A preparations have found an increasing number of clinical uses for a large variety of neuromuscular disorders and dermatological conditions. The accurate determination of potency in the clinical application of botulinum toxins is critical to ensuring clinical efficacy and safety, and is currently achieved by using a lethal dose (LD50) assay in mice. Ethical concerns and operational constraints associated with this assay have prompted the development of alternative assay systems that could potentially lead to its replacement. As one such alternative, we describe the development and evaluation of a novel ex vivo assay (the Intercostal Neuromuscular Junction [NMJ] Assay), which uses substantially fewer animals and addresses ethical concerns associated with the LD50 assay. The assay records the decay of force from electrically-stimulated muscle tissue sections in response to the toxin, and thus combines the important mechanisms of receptor binding, translocation, and the enzymatic action of the toxin molecule. Toxin application leads to a time-related and dose-related reduction in contractile force. A regression model describing the relationship between the applied dose and force decay was determined statistically, and was successfully tested as able to correctly predict the potency of an unknown sample. The tissue sections used were found to be highly reproducible, as determined through the innervation pattern and the localisation of NMJs in situ. Furthermore, the efficacy of the assay protocol to successfully deliver the test sample to the cellular target sites, was critically assessed by using molecular tracer molecules.

Purification and characterization of arginine kinase from the American cockroach (Periplaneta americana).

The isolation and characterization of homogeneous arginine kinase from the cockroach is reported. The purification protocol produces 6.6 mg of pure enzyme from 6.8 g of whole cockroach. The purified enzyme cross-reacts with a heterologous antibody and monoclonal antibody against arginine kinase from the shrimp. Both antibody preparations also cross-react with extracts from several species known to contain monomeric arginine kinase, but fail to react with extracts from organisms containing dimeric arginine kinase. Cockroach arginine kinase has a molecular mass of approximately 43,000 determined from measurements by gel filtration and gel electrophoresis. Compared with other arginine kinases, the enzyme from the cockroach is relatively thermostable (50% activity retained at 50 degrees C for 10 min) and has a pH optima of 8.5 and 6.5-7.5, for the forward and reverse reactions, respectively. Treatment with 5,5'dithiobis[2-nitrobenzoic acid] indicates that arginine kinase has a single reactive sulfhydryl group and, interestingly, the reaction is biphasic. The Michaelis constants for the phosphagen substrates, arginine: 0.49 mM, phosphoarginine: 0.94 mM, and nucleotide substrates MgATP: 0.14 mM, MgADP: 0.09 mM, are in the range reported for other arginine kinases. A 1% solution of pure enzyme has an absorbance of 7.0 at 280 nm. Calculations based on circular dichroic spectra indicate that arginine kinase from the cockroach has 12% alpha-helical structure. The intrinsic protein fluorescence emission maximum at 340 nm suggests that tryptophan residues are below the surface of the protein and not exposed to solvent. Arginine kinase from the cockroach and shrimp are known to be deleterious immunogens towards humans. The availability of pure protein, its characterization and potential regulation of activity, will be useful in developing agents to control the cockroach population and its destructive role in agriculture and human health.