Audrey C. Ko

Deducing the pathogenic contribution of recessive ABCA4 alleles in an outbred population

Accurate prediction of the pathogenic effects of specific genotypes is important for the design and execution of clinical trials as well as for meaningful counseling of individual patients. However, for many autosomal recessive diseases, it can be difficult to deduce the relative pathogenic contribution of individual alleles because relatively few affected individuals share the same two disease-causing variations. In this study, we used multiple regression analysis to estimate the pathogenicity of specific alleles of ABCA4 in patients with retinal phenotypes ranging from Stargardt disease to retinitis pigmentosa. This analysis revealed quantitative allelic effects on two aspects of the visual phenotype, visual acuity (P < 10−3) and visual field (P < 10−7). Discordance between visual acuity and visual field in individual patients suggests the existence of at least two non-ABCA4 modifying factors. The findings of this study will facilitate the discovery of factors that modify ABCA4 disease and will also aid in the optimal selection of subjects for clinical trials of new therapies.

The aging face

Advancements in technology and medicine have led to a greater life expectancy and a corresponding increased interest in the mechanisms and prevention of aging. Because of its central role in human perception of age and emotion, the aging face generates a high demand for understanding the etiology of senescence-related changes. There are effective nonsurgical and surgical methods available for those seeking functional or cosmetic facial rejuvenation.

Upper Eyelid Blepharoplasty: Evaluation, Treatment, and Complication Minimization

Abstract Upper eyelid blepharoplasty is one of the most common procedures performed worldwide for both functional and cosmetic indications. There is a high rate of patient satisfaction; however, in this era of social media, patient expectations are higher than ever. Todays digitally savvy patients expect perfect outcomes with no complications and rapid recovery. To achieve optimal results, a careful preoperative evaluation and sound surgical technique is essential for minimizing complications. Here the authors review their approach to the management of the blepharoplasty patient.

Novel Pigtail Cannula for a Canalicular-Involving Eyelid Laceration.

An 89-year-old woman presented with a canalicular-involving laceration/avulsion of the right lower eyelid after a fall. The inferior canaliculus was severed deep within the wound, and the ends were difficult to identify. Novel pigtail cannulas, designed by the authors, were used for lacrimal system intubation and suture passage. Satisfactory cosmetic and functional results were achieved. These cannulas facilitate repair by integrating multiple functionalities in a single instrument. Once a cannula has been inserted and rotated, the location of fluid egress provides important clues. If injected saline appears in the nasopharynx but not in the wound, absence of a common canaliculus can be suspected. Injection of viscoelastic, air or fluorescein-impregnated saline also permits easier identification of the cut end of the canaliculus within the wound and facilitates appropriate rotation of the pigtail.

Ocular findings and treatment of a young boy with Coats' plus

The authors describe a 34-month-old boy who presented with a bilateral and asymmetric exudative retinopathy with similarities to Coats’ disease. The patient’s medical history was remarkable for hypotonia, developmental delay, seizures, and intracranial calcifications. Genetic testing revealed a diagnosis of Coats’ plus. This rare genetic disease should be in the differential diagnosis in patients who present with a bilateral and asymmetric Coats’-like retinopathy in the presence of other systemic abnormalities.

Management of Through-and-Through Penetrating Skull Injury: A Railroad Spike That Transgressed the Anterior Skull Base

BACKGROUND Penetrating injuries involving foreign objects that transgress the entirety of the human skull present challenges in the management of vascular injuries, infectious risk, cerebrospinal fluid leak, and cosmetic repair. Ultimately, effective management of these injuries requires a multidisciplinary team and judicious surgical planning. CASE DESCRIPTION Here we present the treatment of a patient who experienced a penetrating injury from a railroad spike, with entry and exit points involving the left and right anterior aspects of the temporal fossa, respectively. CONCLUSIONS The rationale for management decisions is reviewed in the context of the published literature.

Transcriptome Analysis of Orbital Adipose Tissue in Active Thyroid Eye Disease Using Next Generation RNA Sequencing Technology.

Objective: This study utilized Next Generation Sequencing (NGS) to identify differentially expressed transcripts in orbital adipose tissue from patients with active Thyroid Eye Disease (TED) versus healthy controls. Method: This prospective, case-control study enrolled three patients with severe, active thyroid eye disease undergoing orbital decompression, and three healthy controls undergoing routine eyelid surgery with removal of orbital fat. RNA Sequencing (RNA-Seq) was performed on freshly obtained orbital adipose tissue from study patients to analyze the transcriptome. Bioinformatics analysis was performed to determine pathways and processes enriched for the differential expression profile. Quantitative Reverse Transcriptase-Polymerase Chain Reaction (qRT-PCR) was performed to validate the differential expression of selected genes identified by RNA-Seq. Results: RNA-Seq identified 328 differentially expressed genes associated with active thyroid eye disease, many of which were responsible for mediating inflammation, cytokine signaling, adipogenesis, IGF-1 signaling, and glycosaminoglycan binding. The IL-5 and chemokine signaling pathways were highly enriched, and very-low-density-lipoprotein receptor activity and statin medications were implicated as having a potential role in TED. Conclusion: This study is the first to use RNA-Seq technology to elucidate differential gene expression associated with active, severe TED. This study suggests a transcriptional basis for the role of statins in modulating differentially expressed genes that mediate the pathogenesis of thyroid eye disease. Furthermore, the identification of genes with altered levels of expression in active, severe TED may inform the molecular pathways central to this clinical phenotype and guide the development of novel therapeutic agents.

Orbital fat regeneration following hormonal treatment of metastatic breast carcinoma

ABSTRACT Enophthalmos in the setting of breast cancer metastatic to the orbit results primarily from the disease pathogenesis, or secondary to treatment effects. Orbital volume restoration and fat regeneration following endocrine treatment monotherapy has not been previously reported. A 76- year-old previously healthy female presented with progressive right enophthalmos secondary to metastatic lobular breast carcinoma. Treatment with an aromatase inhibitor (letrozole) resulted in tumor regression and orbital fat restoration with a corresponding improvement in orbital volume and enophthalmos on clinical exam. The patient is alive on continued letrozole with no progressive disease ten years after diagnosis. This case illustrates the resilience of orbital soft tissues and ability of orbital fat to regenerate in face of breast cancer metastasis. We hypothesize that endocrine monotherapy, and avoidance of radiation therapy, allowed for differentiation of remaining orbital stem cells, and facilitated the fat regenerative process.

Incidence of diplopia after division and reattachment of the inferior oblique muscle during orbital fracture repair

BACKGROUND Wide surgical access to the orbital floor and medial wall is often impaired by the course of the inferior oblique muscle. There is no current consensus on the optimal surgical approach for exposure, and techniques involving inferior oblique division are generally shunned for concern of possible complications. OBJECTIVE To determine the safety and outcomes of inferior oblique division and reattachment for surgical access to the orbital floor and medial wall during orbital fracture repair. METHODS Retrospective, single-center, review of 85 patients that underwent orbital floor, medial wall or combined fracture repair with division and reattachment of the inferior oblique near its origin. Measured characteristics include surgical approach, type of surgery, time to surgery, pre- and post-operative diplopia, enophthalmos, and complications. RESULTS Forty-five patients (52.9%) with no pre-operative diplopia were followed up for a mean of six months. Of these, six patients (13.3%) developed post-operative binocular diplopia that resolved in all patients on an average of three months (range 2-6 months). No patients developed torsional diplopia. One patient developed a hematoma two years later attributable to capsular contraction around the implant. CONCLUSION Division and reattachment of the inferior oblique muscle is a safe method that allows for panoramic surgical visualization of the inferior and medial orbit.

Orbitocutaneous Fistula Secondary to Buried Polyethylene Mesh Implant 12 Years After Injury.

Fabric monofilament polyethylene mesh is an implant primarily used in the repair of abdominal and chest walls. However, there have been isolated reports of using this implant in facial reconstruction. The authors describe a patient who underwent prior orbital floor fracture repair with polyethylene mesh and subsequently developed a recurrent orbital abscess 12 years later. Despite incorporation of the fabric monofilament polyethylene mesh within healed bone, an orbitocutaneous fistula developed after a secondary injury, causing hyperglobus and cicatricial lower eyelid retraction.