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Performing a genome-wide association study (GWAS) with a binary phenotype using family data is a challenging task. Using linear mixed effects models is typically unsuitable for binary traits, and numerical approximations of the likelihood function may not work well with rare genetic variants with small counts. Additionally, imbalance in the case-control ratios poses challenges as traditional statistical methods such as the Score test or Wald test perform poorly in this setting. In the last couple of years, several methods have been proposed to better approximate the likelihood function of a mixed effects logistic regression model that uses Saddle Point Approximation (SPA). SPA adjustment has recently been implemented in multiple software, including GENESIS, SAIGE, REGENIE and fastGWA-GLMM: four increasingly popular tools to perform GWAS of binary traits. We compare Score and SPA tests using real family data to evaluate computational efficiency and the agreement of the results. Additionally, we compare various ways to adjust for family relatedness, such as sparse and full genetic relationship matrices (GRM) and polygenic effect estimates. We use the New England Centenarian Study imputed genotype data and the Long Life Family Study whole-genome sequencing data and the binary phenotype of human extreme longevity to compare the agreement of the results and tools’ computational performance. The evaluation suggests that REGENIE might not be a good choice when analyzing correlated data of a small size. fastGWA-GLMM is the most computationally efficient compared to the other three tools, but it appears to be overly conservative when applied to family-based data. GENESIS, SAIGE and fastGWA-GLMM produced similar, although not identical, results, with SPA adjustment performing better than Score tests. Our evaluation also demonstrates the importance of adjusting by full GRM in highly correlated datasets when using GENESIS or SAIGE.

Orbital implant extrusion is a known complication following evisceration and enucleation. In this case report, we present a 45-year-old woman who presented with a left silicone implant exposure and infection 2 years following evisceration with saddle nose on examination. CT of the maxillofacial bones without contrast showed bilateral soft tissue infiltration around the superior recti muscles, as well as a nasal septum perforation from extensive sinus disease. Left orbitotomy revealed a small fibrotic mass near the orbital roof. Biopsy and serology results were consistent with granulomatosis with polyangiitis.

Optic nerve sheath fenestration (ONSF) is a surgical technique commonly and effectively employed in the treatment of recalcitrant, vision-threatening papilledema. Unilateral blindness, a known risk of unilateral ONSF widely cited with 1%-2% incidence. In this case, a 58-year-old patient who presented symptomatic with bilateral hemorrhagic papilledema unresponsive to medical therapy underwent uneventful unilateral ONSF via standard superomedial eyelid crease incision. The patient presented postoperatively with severe bilateral vision loss. Workup revealed widespread metastatic malignant disease involving the optic chiasm and optic nerve sheath.

Purpose To report a series of patients with extra-ocular movement restriction and diplopia after orbital fracture repair, and determine the effect of timing of repair and the type of implant used. Methods A chart review was conducted identifying all patients > 18 years of age at our institution between June 2005 and June 2008 who underwent orbital fracture repair, and presented with clinically significant diplopia and extra-ocular movement restriction persisting longer than one month after repair. Data collected included timing of repair, implant used within the orbit, and need for revision. Results Ten patients were identified with a mean time to primary orbital fracture repair at 9 days (range 1–48). Seven patients underwent revision of their orbital fracture repair with removal of the previously placed implant and replacement with non-porous 0.4 mm Supramid Foil, whereas one patient underwent lateral and inferior rectus recessions without revision of primary fracture repair. Titanium mesh was the intra-orbital implant found in all patients requiring revision of orbital fracture repair. All revisions resulted in resolution of clinically significant diplopia. Conclusions Clinically significant diplopia and extra-ocular movement restriction is not an uncommon complication after orbital fracture repair. In our series, there was a strong association between these complications and the use of porous titanium mesh implants. Revision of fractures significantly improved diplopia in all but one patient. This suggests that meticulous fracture repair and the use of non-porous implants primarily or secondarily may preclude the need for strabismus surgery after orbital trauma.