NAT1 genetic variation increases asthma risk in children with secondhand smoke exposure.

OBJECTIVE: We previously reported that children exposed to secondhand smoke (SHS) that carried variants in the NAT1 gene had over two-fold higher hair cotinine levels. Our objective was to determine if NAT1 polymorphisms confer increased risk for developing asthma in children exposed to SHS. METHODS: White participants in the Cincinnati Childhood Allergy and Air Pollution Study (n = 359) were genotyped for 10 NAT1 variants. Smoke exposure was defined by hair cotinine and parental report. Asthma was objectively assessed by spirometry and methacholine challenge. Findings were replicated in the Genomic Control Cohort (n = 638). RESULTS: Significant associations between 5 NAT1 variants and asthma were observed in the CCAAPS exposed group compared to none in the unexposed group. There was a significant interaction between NAT1 rs13253389 and rs4921581 with smoke exposure (p = 0.02, p = 0.01) and hair cotinine level (p = 0.048, p = 0.042). Children wildtype for rs4921581 had increasing asthma risk with increasing hair cotinine level, whereas those carrying the NAT1 minor allele had an increased risk of asthma regardless of cotinine level. In the GCC, 13 NAT1 variants were associated with asthma in the smoke-exposed group, compared to 0 in the unexposed group, demonstrating gene-level replication. CONCLUSIONS: Variation in the NAT1 gene modifies asthma risk in children exposed to secondhand-smoke. To our knowledge, this is the first report of a gene-environment interaction between NAT1 variants, smoke exposure, cotinine levels, and pediatric asthma. NAT1 genotype may have clinical utility as a biomarker of increased asthma risk in children exposed to smoke.

Isolated choroidal melanocytosis: clinical update on 37 cases.

PURPOSE: Isolated choroidal melanocytosis is a congenital melanocytic hyperpigmentation involving the choroid that is not associated with iridic or scleral features of ocular melanocytosis. The purpose of this work was to describe the clinical features and course of a relatively large series of patients with this disorder. METHODS: A retrospective clinical study of 37 patients with isolated choroidal melanocytosis encountered in a single practice 1986-2018 was done. All lesions were 5 mm or larger in the largest basal diameter, homogeneously melanotic, and completely flat by conventional ocular ultrasonography. RESULTS: The 37 patients ranged in age from 2 weeks to 87 years (mean 31.5 years, median 18 years) at initial diagnosis of the melanotic choroidal lesion. Arc length largest basal diameter of the melanotic choroidal lesion ranged from 5.5 to 37 mm (mean 14.6 mm, median 13 mm). The lesion extended beneath the fovea in 18 eyes and to the optic disc margin in 6 eyes. Ten of the lesions straddled the ocular equator, but the center point of all of the lesions was posterior to the equator. The retina was fully attached and appeared normal over the melanotic choroidal lesion in each of these eyes. None of the melanotic choroidal lesions exhibited clumps of orange pigment or drusen on its surface. The lesion was unilateral and unifocal in 36 of the 37 patients. One patient had bilateral choroidal melanocytosis that was isolated in one eye but associated with partial iris melanocytosis in the fellow eye. Three adult patients had a choroidal melanoma localized to the patch of choroidal melanocytosis at baseline. One other adult patient had a choroidal melanoma in the fellow eye at baseline. One pediatric patient had viable unilateral non-familial retinoblastoma in the fellow eye and two adult patients had a classic choroidal nevus in the fellow eye. None of the flat patches of choroidal melanocytosis that were monitored periodically after initial diagnosis expanded appreciably during follow-up ranging from 4.9 months to 15.2 years (mean 5.0 years, median 2.3 years). CONCLUSIONS: Isolated choroidal melanocytosis is a distinct clinical entity that must be distinguished from broad-based choroidal nevus, choroidal melanocytoma, small choroidal malignant melanoma, acquired bilateral patchy-streaky choroidal melanocytic fundopathy associated with disorders such as cutaneous vitiligo and Waardenburg syndrome, acquired bilateral zonal choroidal melanocytic fundopathy, and diffuse uveal melanocytic proliferation associated with systemic cancer. This disorder appears to predispose affected eyes to development of choroidal melanoma arising from the hypermelanotic patch.

Meibomian Gland Morphology Among Patients Presenting for Refractive Surgery Evaluation.

PURPOSE: To report the prevalence of meibomian gland atrophy and gland tortuosity in patients presenting for refractive surgery evaluation. METHODS: Cross-sectional study of consecutive patients presenting for refractive surgery evaluation at the Duke Eye Center from December 2018 through January 2020. All patients underwent clinical examination and meibography imaging (Lippiview II, Johnson and Johnson Vision, CA) of the lower eyelids bilaterally. Images were graded by a masked rater using a previously validated 5-point meiboscale (0-4) for gland atrophy and 3-point scale for gland tortuosity (0-2). Lipid layer thickness and partial blinks were also recorded. RESULTS: One hundred and twenty patients (49 male) aged 21 to 62 years (mean 35.2 ± 9.2 years) were reviewed. The mean meiboscale was 1.1 ± 1.0 and the mean tortuosity score was 1.0 ± 0.7. Among all patients, 72.5% (n = 87) had any evidence of meibomian gland atrophy (meiboscale >0) and 69.2% (n = 83) had any evidence of meibomian gland tortuosity (tortuosity grade ≥1). The majority of patients (n = 52) with gland atrophy had mild gland atrophy (meiboscale = 1). The mean meiboscale was 0.89 ±0.79 and 1.38 ±1.07 for those <35 years and >/= 35 years old, respectively (p = 0.01). There was a moderate positive relationship between meiboscale and tortuosity (Spearman's rho 0.3829, p <0.001). CONCLUSION: Meibomian gland atrophy is a common occurrence in patients presenting for refractive surgery evaluation. Clinicians should consider incorporating meibography as part of refractive surgery evaluation, and proactively treat meibomian gland disease given the known association between meibomian gland dysfunction, dry eye disease, and the potential for suboptimal post-operative outcomes.

Dexamethasone 0.4mg Sustained-Release Intracanalicular Insert in the Management of Ocular Inflammation and Pain Following Ophthalmic Surgery: Design, Development and Place in Therapy.

Inflammation and pain are two prevalent findings after ocular surgery. Corticosteroids are widely administrated as a core treatment to control post-surgical inflammation and pain. Improper patient adherence to post-operative eye drop regimens, limited bioavailability of topical eye drops, and the negative impact of preservatives used in many of these eye drops, has made a strong case for novel therapies in the treatment of post-operative pain and inflammation. This review of the literature will focus on the role of intracanalicular sustained-release dexamethasone (Dextenza, Ocular Therapeutix, Bedford, MA, USA) for the management of ocular inflammation and pain.

Cataract surgery in patients with left ventricular assist devices.

PURPOSE: To determine the safety and efficacy of cataract surgery in patients with left ventricular assist devices (LVADs). SETTING: Duke Eye Center, Durham, North Carolina, USA. DESIGN: Retrospective case series. METHODS: Electronic medical records were used to collect patient demographics, preoperative planning, intraoperative details, and postoperative outcomes of patients with LVADs who underwent cataract surgery between March 2012 and August 2019. RESULTS: A total of 53 cataract surgeries were identified involving 31 patients. Most patients were men (n = 27) and white (n = 25) with a mean age of 69.5 years. Preoperative biometry was unchanged from standard protocol. Femtosecond laser, intraoperative aberrometry, and/or a premium IOL was used in 25 cases (47.2%) . Patients were on warfarin, warfarin plus aspirin, and warfarin plus clopidogrel in 51.6% (n = 16), 45.2% (n = 14), and 3.2% (n = 1) of cases, respectively. Patients underwent topical anesthesia with monitored anesthesia care from an experienced LVAD team as planned with no episodes of hemodynamic instability, respiratory compromise, or intraoperative adverse events related to the LVAD. All patients were discharged the same day as surgery. There were no hospitalizations or deaths within 30 days that were attributed to the cataract procedure. At 1 month postoperatively, 61.1% of eyes were ±0.5 diopter of their predicted spherical equivalent (n = 11/18), with a high proportion of patients returning to local providers for postoperative care. CONCLUSIONS: Cataract surgery was safe and feasible in patients with LVADs when performed with additional perioperative considerations and in conjunction of an experienced LVAD team. The presence of LVAD itself was not found to be a contraindication for cataract surgery.

Optical Quality and Tear Film Analysis Before and After Intranasal Stimulation in Patients with Dry Eye Syndrome.

PURPOSE: To evaluate the optical quality and tear film quality in patients with dry eye syndrome (DES) before and after using an intranasal neurostimulation device to stimulate tear production. METHODS: Cross-sectional review of 33 eyes in 21 patients with DES who underwent optical quality and tear film analysis as part of their routine dry eye evaluation pre- and post-neurostimulation trial in office. Optical quality was assessed by measuring the objective scattering index (OSI) and modulation transfer function (MTF). The time to blink and mean tear film OSI were used to analyze the tear film. RESULTS: Optical quality after the use of the intranasal neurostimulator improved with an average decrease (improvement) in OSI of 0.30±0.68 (P=0.015) and an average increase (improvement) in MTF of 2.12±9.2 (P=0.15). Pre-intranasal neurostimulation OSI had a positive correlation with age (Spearman's rho 0.60, p < 0.001), while MTF had a negative correlation (Spearman's rho -0.38, p = 0.03). Pre-intranasal neurostimulation OSI had a negative correlation with MTF (Spearman's rho -0.85, p < 0.001) and a positive correlation with tear film mean OSI (Spearman's rho 0.85, p <0.001). CONCLUSION: The optical quality of patients with DES is improved with the use of intranasal neurostimulation for tear production, and there was a trend towards improved MTF though not statistically significant. Future studies are needed to follow patients longitudinally.

Management of a rhegmatogenous retinal detachment in a pregnant patient.

PURPOSE: To describe the management of a rhegmatogenous retinal detachment (RRD) in a pregnant patient. OBSERVATIONS: A 30-year-old, 26-week pregnant female presented with curtain vision loss in the left eye. Exam findings were significant in the left eye for an inferior fovea-sparing RRD. Care was coordinated and discussed with anesthesia and OB/GYN. The patient underwent surgery with monitored anesthesia care and a 41 scleral buckle, cryotherapy and C3F8 gas. The retina remained attached at 4 months post-operatively. A healthy girl was delivered via spontaneous vaginal delivery at 39 weeks. CONCLUSION: Safe and successful treatment of RRD in pregnant patients can be achieved with careful coordination between ophthalmology, anesthesia, and obstetrics. An understanding of pregnancy specific considerations is important in order to optimize patient outcomes.

Consolidation of Imaging Modalities Utilizing Digitally Assisted Visualization Systems: The Development of a Surgical Information Handling Cockpit.

The management of vitreoretinal cases is ever-evolving, paralleled by rapid advancements in operative imaging modalities. In this article, we describe an advanced application of digitally assisted vitreoretinal surgery (DAVS) that involves the consolidation of pre-existing ancillary imaging technology into a single same-screen viewing platform. Forty-four eyes of 44 patients were operated using same screen simultaneous viewing of the primary three-dimensional high definition (3DHD) surgical field and simultaneous auxiliary video feed viewing of all currently approved ocular endoscopy (n=12), intraoperative optical coherence tomography (iOCT) units (n=24), or computer feeds from the EHR/image management software (n=8). All surgeries were successful with excellent functional and anatomic outcomes. DAVS facilitated same screen viewing of multiple video/information feeds was notable for improved ergonomics, surgical efficiency, and precision when compared to viewing the surgical field and auxiliary video feeds separately. We describe a new concept for the vitreoretinal operating room - a DAVS-based surgical information handling cockpit - integrating FDA approved ocular endoscopy (n=1), microscope-integrated iOCT units (n=3), and one EHR/Image management solution with the primary surgical field 3DHD feed. We suggest same screen viewing of multiple video and other clinical information feeds is a promising modality that may be considered in the management of patients with surgical vitreoretinal disease and should be purposefully incorporated into future iterations of DAVS technology platforms.