Absence of systemic immune response to adenovectors after intraocular administration to children with retinoblastoma.

The ocular environment has been shown to induce tolerance to locally administered antigens. We therefore investigated whether there was a systemic immune response against adenoviral vectors injected into the vitreous of retinoblastoma patients enrolled in a phase 1 clinical trial of adenoviral-mediated thymidine kinase gene transfer. Sections of enucleated eyes were immunostained with antibodies against inflammatory cells. A trend toward increasing numbers of plasma cells, T cells, macrophages, and antigen-presenting cells was observed in the injected subjects' eyes, but systemically, there was no significant increase in the number of adenovirus-specific cytotoxic T lymphocytes (CTLs) or in adenovirus neutralizing antibodies. Therefore, in contrast to studies showing significant immunogenicity of Ad-RSVtk following injection into extraocular tumors, injection into the eye produces only a mild local inflammatory response without evidence of systemic cellular or humoral immune responses to adenovirus.

Decreased retinal nerve fibre layer thickness detected by optical coherence tomography in patients with ethambutol-induced optic neuropathy.

BACKGROUND: It is difficult to assess the degree of optic nerve damage in patients with ethambutol-induced optic neuropathy, especially just after the onset of visual loss, when the optic disc typically looks normal. AIM: To evaluate changes in retinal nerve fibre layer thickness (RNFLT) using optical coherence tomography (OCT) in patients with optic neuropathy within 3 months of cessation of ethambutol treatment. DESIGN: A retrospective observational case series from a single neuro-ophthalmology practice. METHODS: 8 patients with a history of ethambutol-induced optic neuropathy were examined within 3 months after stopping ethambutol treatment. All patients underwent a neuro-ophthalmologic examination, including visual acuity, colour vision, visual fields and funduscopy. OCT was performed on both eyes of each patient using the retinal nerve fibre layer analysis protocol. RESULTS: The interval between cessation of ethambutol treatment and the initial visit ranged from 1 week to 3 months. All patients had visual deficits characteristic of ethambutol-induced optic neuropathy at their initial visit, and the follow-up examination was performed within 12 months. Compared with the initial RNFLT, there was a statistically significant decrease in the mean RNFLT of the temporal, superior and nasal quadrants (p = 0.009, 0.019 and 0.025, respectively), with the greatest decrease in the temporal quadrant (mean decrease 26.5 mum). CONCLUSIONS: A decrease in RNFLT is observed in all quadrants in patients with ethambutol-induced optic neuropathy who have recently discontinued the medication. This decrease is most pronounced in the temporal quadrant of the optic disc.

Very high-frequency ultrasound analysis of non-contact holmium laser thermal keratoplasty treatment spots.

PURPOSE: To objectively measure the corneal treatment spots in vivo using very high-frequency ultrasound (VHFU) after non-contact laser thermal keratoplasty (LTK) to better understand the variability and regression of refractive outcomes. METHODS: In an institutional setting, VHFU was performed on 128 spots (8 eyes of 4 patients) using an immersion scanning technique 1 to 2 years after LTK with a single element focused transducer (50 MHz arc scanning ultrasound). Biometric techniques were used to evaluate the treatment spot depth, corresponding corneal thickness, and spot profile between patients, eyes (left/right), and by location on the cornea. The identical technique was used in a rabbit immediately after LTK to compare ultrasound versus histologic findings. RESULTS: The mean treatment spot penetration depth ranged between 0.373 and 0.533 mm, representing 64% to 78% of the corneal thickness compared to previous reports of 80% to 90%. Treatment spot depth, the corresponding corneal thickness, and percentage of overall cornea penetrated differed significantly across patients. Treatment spot depth was not significantly related to the level of applied laser energy (230 to 258 mJ) (0.082 Pearson sign). Spot profiles were not uniformly cone-shaped; W- and wedge-shaped were also identified. Ultrasound findings in the rabbit were similar to histology results and confirmed evidence of epithelial remodeling. CONCLUSIONS: Very high-frequency ultrasound of 128 treatment spots after non-contact LTK demonstrates epithelial remodeling and inconsistencies in penetration depth and profile.