Congenital macular scars in siblings from CLDN19 mutations.

We report 2 consecutive siblings who presented with unilateral and bilateral macular scars, respectively (initially presumed in the older sibling to be from congenital toxoplasmosis), who also developed chronic kidney disease. Both underwent genetic testing and were positive for a mutation in CLDN19, confirming the diagnosis of familial hypomagnesemia with hypercalciuria and nephrocalcinosis with severe ocular involvement. One of our patients had the unique finding of mild foveal hypoplasia, which is not typically associated with CLDN19 mutations.

Corneal indices following photorefractive keratectomy in children at least 5 years after surgery.

PURPOSE: To evaluate long-term corneal outcomes in pediatric patients who underwent photorefractive keratotomy (PRK) for the treatment of refractive amblyopia. METHODS: In this prospective interventional case series, children with refractive amblyopia underwent PRK between January 1, 2007, and December 31, 2011, at Texas Children's Hospital's Department of Ophthalmology, a single tertiary eye center, and were followed for at least 5 years after surgery. Main outcome measures were 5+ years postoperative indices of corneal thickness, keratometry, degree of corneal haze, and presence or absence of keratectasia. RESULTS: Twelve eyes of 8 subjects aged 3-9 years who underwent PRK and were followed for at least 5 years were included. The mean PRK treatment dose was 8.46 D for the myopic cohort and 4.49 D for the hyperopic cohort, which removed an average of 72 µm of corneal stromal tissue in addition to the 50 µm of corneal epithelium that was removed prior to laser ablation. The mean corneal thickness was 563 µm preoperatively, which decreased to 441 µm immediately following the PRK. The mean corneal thickness 5+ years after PRK was stable, at 498 µm, because of epithelial regrowth. None of the subjects developed visually significant corneal haze or topographic evidence of keratectasia. CONCLUSIONS: In this study cohort, there were no topographic signs of keratectasia or corneal haze in children treated with PRK for high refractive error 5 years or more after surgery.

Spontaneous choroidal hemorrhage in a patient on dabigatran etexilate (Pradaxa).

PURPOSE: To report the first known case of spontaneous choroidals in association with a patient on dabigatran etexilate. METHODS: Observational case report. RESULTS: An 82-year-old man on 150 mg dabigatran etexilate by mouth twice a day for atrial fibrillation developed spontaneous choroidal hemorrhage in his left eye. No other causes were found after careful history and examination. CONCLUSION: Dabigatran is a popular new alternative to warfarin that has no blood monitoring or reversal agent. Physicians should be aware of this new medication and its possible hemorrhagic complications.

Development of an advanced nomogram for myopic astigmatic wavefront-guided laser in situ keratomileusis (LASIK).

BACKGROUND AND OBJECTIVE: To identify the relationship between preoperative parameters and postoperative overcorrection or undercorrection in eyes with myopic astigmatism treated with wavefront-guided laser in situ keratomileusis (LASIK), and to develop an advanced surgical nomogram. PATIENTS AND METHODS: A retrospective chart review of 468 eyes that underwent wavefront-guided LASIK for myopia with astigmatism with the Alcon LADARVision 4000 (Alcon Laboratories, Fort Worth, TX), of which 235 had flaps created by microkeratome (OneUse; Moria Surgical, Doylestown, PA) and 233 by femtosecond laser (Intralase; AMO, Santa Ana, CA). Manifest sphere, cylinder, and spherical equivalent were recorded preoperatively and 3 months postoperatively. Various parameters from patient records were analyzed to identify which had greatest influence on outcomes. RESULTS: Manifest spherical equivalent was the most important predictor of surgical overcorrection, with the second being spherical aberration. In both groups, there was a statistically significant (P < .0001) correlation of spherical aberration with the amount of overcorrection. Using these two parameters, compensatory nomograms were derived. CONCLUSION: Surgical overcorrection in wavefront-guided LASIK for myopic astigmatism correlates positively with the amount of spherical equivalent treated and preoperative spherical aberration. Nomograms incorporating spherical aberration may improve accuracy of outcomes.

Optimization of adenoviral vector-mediated transgene expression in the canine brain in vivo, and in canine glioma cells in vitro.

Expression of the immune-stimulatory molecule Fms-like tyrosine kinase 3 ligand (Flt3L) and the conditional cytotoxic enzyme herpes simplex virus type 1 thymidine kinase (HSV1-TK) provides long-term immune-mediated survival of large glioblastoma multiforme (GBM) models in rodents. A limitation for predictive testing of novel antiglioma therapies has been the lack of a glioma model in a large animal. Dogs bearing spontaneous GBM may constitute an attractive large-animal model for GBM, which so far has remained underappreciated. In preparation for a clinical trial in dogs bearing spontaneous GBMs, we tested and optimized adenovirus-mediated transgene expression with negligible toxicity in the dog brain in vivo and in canine J3T glioma cells. Expression of the marker gene beta-galactosidase (beta-Gal) was higher when driven by the murine (m) than the human (h) cytomegalovirus (CMV) promoter in the dog brain in vivo, without enhanced inflammation. In the canine brain, beta-Gal was expressed mostly in astrocytes. beta-Gal activity in J3T cells was also higher with the mCMV than the hCMV promoter driving tetracycline-dependent (TetON) transgene expression within high-capacity adenovirus vectors (HC-Ads). Dog glioma cells were efficiently transduced by HC-Ads expressing mCMV-driven HSV1-TK, which induced 90% reduction in cell viability in the presence of ganciclovir. J3T cells were also effectively transduced with HC-Ads expressing Flt3L under the control of the regulatable TetON promoter system, and as predicted, Flt3L release was stringently inducer dependent. HC-Ads encoding therapeutic transgenes under the control of regulatory sequences driven by the mCMV promoter are excellent vectors for the treatment of spontaneous GBM in dogs, which constitute an ideal preclinical animal model.