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ABSTRACTTakeda has developed a live-attenuated dengue tetravalent vaccine candidate (TAK-003) which has been shown to be immunogenic with acceptable reactogenicity in phase 1 trials. In agreement with World Health Organization prequalification requirements for dengue vaccines, Takeda has manufactured a lyophilized formulation of TAK-003 that allows stable storage at +2°C to +8°C. This randomized, double-blind, phase 2 study (NCT02193087) was performed in 1002 healthy dengue-naïve adults, 18–49 years of age, across seven centers in the USA to compare the safety and immunogenicity of one or two doses of a lyophilized TAK-003 formulation with the liquid TAK-003 formulation used in previous phase 1 studies. The primary objective was to show immunologic equivalence in terms of geometric mean titers (GMT) of neutralizing antibodies to the four dengue serotypes one month after one dose of the lyophilized and liquid formulations. Secondary assessments were of safety and seropositivity rates, including after a second dose. The primary endpoint was not met, because immunologic equivalence after one dose was only shown for the DENV-2 serotype. Nonetheless, GMTs and seropositivity rates to all four serotypes were achieved with all formulations after two doses and are in line with what was observed in previous studies. Additionally, in view of the acceptable reactogenicity, with no vaccine-related serious adverse events reported, these data support continuing further clinical development of the lyophilized TAK-003 formulation.

The refractive and visual results of a consecutive series of diamond knife radial keratotomy procedures were evaluated at one year after surgery as part of an ongoing prospective study of radial keratotomy. Of the 972 procedures performed, 656 eyes (67.5%) were examined one year or more after surgery. The average amount of preoperative myopia was 4.4 diopters with a range of 0.6 to 11.9 diopters; 638 (97%) of the eyes had a preoperative uncorrected visual acuity of 20/100 or worse. The mean change in spherical equivalent after one year was 4.5 diopters. One year after surgery, 496 (76%) of the eyes were within 1 diopter of emmetropia; 310 (47%) had uncorrected distance visual acuity of 20/20 or better, 579 (88%) were 20/40 or better, and all but one eye had uncorrected visual acuity improved by at least two Snellen lines. Evaluation of refractive and visual results at the final available examination of those eyes not examined one year after surgery showed that 256 (81%) of the eyes were within 1 diopter of emmetropia; 176 (56%) had uncorrected distance visual acuity of 20/20 or better, and 287 (91%) were 20/40 or better.

• Various doses of a new topical nonsteroidal anti-inflammatory agent, diclofenac sodium, were tested against prednisolone sodium phosphate in a randomized double-masked study to determine comparative efficacy and safety regarding the reduction of postsurgical ocular inflammation. Inflammation was assessed by measuring fluorescein leakage into the anterior chamber using f luorophotometry techniques. Increased leakage in each patient's operated-on eye compared with the unoperated-on control eye was attributed to a breakdown in the blood-aqueous barrier caused by the cataract surgery. Elimination or significant reduction of fluorescein leakage within a treatment group constituted increased efficacy in controlling inflammation. A total of 124 cases were analyzed. There were no preoperative differences among groups in fluorescein leakage. At 1 week after surgery, all three diclofenac groups had significantly less fluorescein leakage compared with the prednisolone group. Mean percent increases were 56% to 118% in diclofenac groups vs 324% in the prednisolone group. No differences among diclofenac concentrations were detected. The differences between prednisolone and diclofenac were also present, although of lesser magnitude, at 3 weeks. This demonstration of increased efficacy of the nonsteroidal anti-inflammatory agent vs prednisolone is promising given the known side effects of ocular steroids.

Purpose:To compare the safety and efficacy of radial keratotomy (RK) and photorefractive keratectomy (PRK) to correct myopia.

Purpose:To determine the degree of corneal thickness variability that may be encountered during routine radial keratotomy (RK) surgery.

Purpose:To determine whether intraoperative unpreserved lidocaine further decreases discomfort or pain during sutureless small incision cataract surgery and intraocular lens (IOL) implantation under topical anesthesia.

• Neodymium-YAG capsulotomy for secondary cataracts can induce acute intraocular pressure rises, possibly by a blocking of the trabecular meshwork by debris. To test a hypothesis that bag-fixated intraocular lenses may act as a barrier to debris, thus reducing pressure rises after YAG capsulotomy, we conducted a study comparing pressures (at 1, 2, 3, 6, and 24 hours after YAG capsulotomy) between bag-fixated and sulcus-fixated cases. There were substantial and statistically significant intraocular pressure rises in the sulcus-fixated group starting at 1 and 2 hours after YAG capsulotomy, and peaking at 3 hours (mean rise, 7.83 mm Hg). There were no such peaks of intraocular pressure rise among bag-fixated cases (mean change, −0.32 mm Hg at 3 hours). There was a weak but significant (r = −.18) correlation between the change 1 hour after YAG capsulotomy in intraocular pressure and percent of enclosure of the intraocular lens optic among bag-fixated cases. Higher proportions (fourfold to fivefold) of cases with sulcus-fixated lenses had significant flare and particulate matter in the anterior chamber, compared with bag-fixated cases.

OBJECTIVE: To evaluate the long-term stability of the refractive outcome after metal-blade radial keratotomy procedures. DESIGN: A cohort of 146 patients who underwent 225 consecutive metal-blade radial keratotomy procedures that were performed under a uniform protocol between November 1979 and August 1981 was monitored prospectively, with 64% of the patients followed up for at least 5 years. MAIN OUTCOME MEASURES: Changes in spherical equivalent and changes in average keratometry were evaluated within the following periods: 3 months to 1 year; 1 to 2 years; 2 to between 3 and 4 years (mean, 3.7 years); between 3 and 4 (mean, 3.7 years) to between 5 and 12 years (mean, 8.5 years); and 1 to between 5 and 12 years (mean, 8.5 years). RESULTS: Total mean change in refraction between 1 year and the average of 8.5 years of follow-up was 1.01 diopters (D) (SD, 1.13 D). At 1 year, 31% of the cases were at least 1 D hyperopic, whereas at an average of 8.5 years, 48% were at least 1 D hyperopic. Fifty-four percent of the cases had shifted in the hyperopic direction by 1 D or more. Stepwise regression analysis failed to identify significant predictive factors for the hyperopic shifts. CONCLUSIONS: The trend toward progressive hyperopic shifts within this cohort has continued with time. Other long-term studies have documented similar, although somewhat smaller, hyperopic shifts among both patients treated with metal-blade and patients treated with diamond-blade procedures. Causative factors for the hyperopic shift have not been identified. It remains to be seen if eyes undergoing current, more cautious surgical approaches to radial keratotomy will also experience this phenomenon.

Purpose:To determine the safety and efficacy of intracameral injections of unpreserved lidocaine to reduce intraocular sensation.