United States

Objective: Robin sequence (RS) is a craniofacial anomaly characterized by a small jaw (micrognathia) with associated posterior displacement of the tongue, which in turn leads to airway obstruction. With advances in fetal imaging, fetuses with micrognathia may now be detected prenatally. This study aims to determine if differences in outcomes exist between infants with Robin sequence who had micrognathia identified on prenatal ultrasound and those who were not noted to have micrognathia until after delivery. 

Study Design: A retrospective case series with chart review was performed to examine a cohort of children with Robin sequence who received care at an urban tertiary medical center between 01/01/2010 and 12/31/2020. Demographic information as well as outcome metrics such as length of stay, number of hospital transfers, age at airway intervention, rates of oral feeding upon discharge home, and whether the child received early intervention services were assessed. 

Results: There were 47 infants with Robin sequence included in the analysis. 40.4% (n=19) were noted to have micrognathia / retrognathia on prenatal ultrasound, and 47.4% (n=9) of these 19 pregnancies were referred to a maternal fetal medicine program and subsequent prenatal consultation with a craniofacial team. As compared to those infants who were not diagnosed with micrognathia until after birth, the 19 infants identified prenatally were significantly less likely to require transfer from birth hospital (p= 0.02) and were more likely to be enrolled in early intervention services (p= 0.02) during infancy. Subgroup analysis of the 19 fetuses noted to have micrognathia suggests that those who were referred to a maternal fetal medicine program and underwent prenatal craniofacial team consultation had fewer hospital transfers and shorter overall lengths of stay when airway intervention was required. 

Conclusions: Prenatal recognition of micrognathia is associated with fewer hospital transfers for the infant prior to discharge home compared to diagnosis of Robin sequence after birth. When Robin sequence is suspected on ultrasound, prenatal consultation with a maternal fetal medicine program and an affiliated craniofacial team may facilitate transfer of perinatal care to a tertiary medical center, thereby avoiding subsequent separation of mother and baby should airway problems develop after delivery and transfer of the newborn be required.

AMA Research Challenge 2022

Prenatal consultation for micrognathia improves timely diagnosis and management of Robin sequence

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Background
Depression and anxiety are highly prevalent in American society. Patients undergoing infertility treatment are at especially high risk for depression and anxiety, and these effects may linger for decades. 

Objective
To determine the risk for anxiety and depression in women seeking IVF for primary infertility and analyze potential corresponding factors. 

Methods
Patients were English-speaking women with a diagnosis of primary infertility seeking first-time IVF recruited from a clinic in Spokane, WA between 4/2020 and 5/2022.
A total of 55 patients (aged 21-44) met criteria and consented to the study. They completed the initial Generalized Anxiety Disorder-7 scale (GAD-7) and Patient Health Questionnaire-9 (PHQ9) prior to treatment via phone. A positive screen for anxiety was a score ≥8, and a positive screen for depression was ≥5.

Results
A total of 22 patients screened positive for either anxiety or mild depression. 13 patients (23%) screened positive for anxiety, and 16 (29%) screened positive for mild depression. 
9 of the 13 patients who screened positive for anxiety, also screened positive for mild depression.
Patients who screened positive for anxiety were on average 31 years old (SD=3.7), while those who screened positive for mild depression were on average 31.5 (SD= 5.0).
29 patients had previously completed an intrauterine insemination, with 9 (31%) screening positive for symptoms of mild depression and 7 (24%) screening positive for anxiety. 

Conclusions
Within the general population 11.3% report regular feelings of anxiety and 4.5% report regular feelings of depression; however, our study showed a 23% prevalence of anxiety and a 29% prevalence of mild depression. There was no significant increased risk for anxiety or depression in those who had previously undergone intrauterine insemination, and the analysis of age as a corresponding factor was limited by the small sample size in this study.
Given the high rates of anxiety and depression seen in patients undergoing IVF compared to the general population, this patient population may benefit from additional mental health support and routine screening throughout treatment.

Screening for Anxiety and Depression in Women Undergoing First-time in Vitro Fertilization (Ivf) for Primary Infertility

Abstract Title
A New Case and Comprehensive Review of the Ophthalmic Manifestations of 172 Individuals with Branchio-Oculo-Facial Syndrome

Background
Branchio-oculo-facial syndrome (BOFS) is an autosomal dominant condition attributable to TFAP2A gene variants. Patients classically present with head and neck anomalies, ocular, and facial malformations. In 2008, TFAP2A gene mutations were first associated with BOFS. To help characterize the most common eye manifestations associated with the syndrome, we present a new case and the results of a comprehensive literature review where we identified the common genetic variants and ophthalmic findings among previously reported patients.

Methods
A search of the PubMed database with the term branchio-oculo-facial syndrome generated 378 articles. We included our patient and identified 172 total patients from the literature. Among these, 102 patients received molecular confirmation. Results were delineated by the following groups: clinical diagnosis only, those with confirmed molecular testing, and total numbers among both groups.

Results
We report a girl with a de novo pathogenic mutation in the TFAP2A gene consistent with BOFS and had similar ophthalmic findings to those reported in the literature, which included cataract, coloboma, hypertelorism, strabismus, and epicanthal folds. The most common pathogenic variants among our patient and individuals with molecular confirmation among past reports were p.R255G, p.A256V, p.R254W, and p.G251E. Common eye abnormalities associated with the syndrome in total numbers among both groups were nasolacrimal duct stenosis (n = 98, 57%), coloboma (n = 76, 46%), anophthalmia/microphthalmia (n = 64, 37%), and cataracts (n = 27, 16%).

Conclusion
Eye abnormalities presented were rather similar when comparing groups, for example, nasolacrimal duct stenosis (60% vs 55% in clinical only and molecular confirmation groups, respectively) and anophthalmia and/or microphthalmia (39% vs 36%) were two common findings among both groups with similar percentages. This supports that the cases identified by clinical suspicion alone without molecular confirmation were likely also accurate. Our patient also had epicanthal folds, a finding previously reported in only 3 patients. This finding could be an underreported ocular adnexa abnormality associated with the phenotype. This analysis provides a comprehensive review of common genetic variants and ophthalmic findings to characterize the most common eye manifestations associated with BOFS. Our report provides incentive to further investigate TFAP2A variants and identify genotype-phenotype correlations.

A New Case and Comprehensive Review of the Ophthalmic Manifestations of 172 Individuals with Branchio-Oculo-Facial Syndrome

Background
Glaucoma is the second leading cause of blindness, affecting 80 million patients globally including 3 million patients in the USA. Elevated intraocular pressure (IOP), caused by the blockage of aqueous humor (AH) outflow from the anterior chamber (AC), is an important risk factor in glaucoma. After medical treatments fail to control IOP, a glaucoma drainage device (GDD) is implanted. Unfortunately, current GDDs have major drawbacks: (1) large sizes requiring extensive surgical dissection, (2) uncontrolled release of AH risking vision loss, and (3) prolonged inflammation and fibrosis leading to 50% failure rate at 5 years. To address this clinical need, our aim was to develop a new GDD called the Squid Glaucoma microShunt (SGS). 
Methods
A 3D model of the SGS was generated using computer-aided-design software ANSYS. SGS is 90% smaller designed to release AH in a slow, sprinkle-like fashion minimizing the complications. To further reduce inflammation, SGS will be coated with a patented low-cost ultrananocrystalline diamond (UNCD) film exhibiting superb biocompatibility. Finally, a pair of patented micro forceps have been designed to facilitate easy insertion of the SGS promoting a 50% reduction in surgery time enabling surgeons to treat more patients efficiently.
We designed an in-silico ANSYS fluidic simulation to study fluid flow and pressure drop. The efficacy of UNCD was tested by coating it on an Ahmed® Shunt and inserting it in a rabbit eye. The control eye had an Ahmed® shunt without UNCD coating. 
Results
The in-silico ANSYS fluidic simulation showed that the SGS reduced IOP by 50% from 17 mmHg to 9 mmHg. At one year, the rabbit eye with a UNCD coated Ahmed® shunt was quiet with low IOP, while the uncoated eye shunt had failed within days because of intense inflammation and scarring. Several SGS and micro forceps prototypes have been fabricated using a Stratasys® 3D-printer and are awaiting laboratory testing. 
Conclusion
Due to the complications associated with current GDDs, only 40% of glaucoma patients undergo surgical interventions. Our minimally invasive SGS implant would make early surgical intervention an option for glaucoma patients with presumably better outcomes and prevent blindness.

A Novel Squid Glaucoma microShunt for Controlled Release of Aqueous Humor

Background
Diagnostic fluorescein angiography (FA) is a routine in-office imaging modality that aids in the diagnosis, monitoring, and treatment of various retina diseases. This imaging procedure requires a standard dose of intravenous injection of 5 mL fluorescein sodium (FS) 10% 500mg. Up to 20% of the population may experience mild to moderate adverse reactions such as nausea and vomiting and less than 1% have experienced a severe reaction of anaphylaxis after receiving FS. Past studies rejected the use of half dose 2.5 mL FS due to poor image quality. With recent updates in scanning laser ophthalmoscopy, a full dose of 5 mL may not be necessary, and half the standard dose may be adequate using newer wide-field angiography. We hypothesize that the incidence of adverse reactions will significantly decrease with half dose FS compared to the standard 5 mL dose.

Methods
A prospective study measuring the incidence of five adverse reactions (ARs) including nausea, vomiting, dizziness, lightheaded, and hot/ warm sensation during and following the procedure with 5 mL (standard) versus 2.5 mL (half dose) FS was compared.

Results
An independent t-test revealed the incidence of having at least one AR was significantly different between groups (p<0.05). 15.8% of individuals who received 5 mL FS experienced at least one AR, compared to 9.1% of individuals who received 2.5 mL FS (n = 202, 253). Of those who received 5 mL FS, 11.9% experienced nausea, 4.5% experienced vomiting, 5.4% experienced lightheadedness, 5.4% experienced dizziness, and 3.5% experienced vomiting compared to 7.5%, 1.6%, 0.8%, 0.4%, and 0% of participants who received 2.5 mL FS, respectively. 

Conclusion
This was a significant decrease in ARs for patients who received half dose FS. This has potential to aid patients who previously could not tolerate the full dose due to ARs.

Analysis of Adverse Reactions Associated with Half Dose of Fluorescein Sodium during Wide-Field Fluorescein Angiography​

Purpose: 
The 13-lined ground squirrel (13-LGS), a cone-dominant hibernator, has emerged as an accessible animal model for vision research. Induction of cone degeneration through exposure to cytotoxic chemicals has revealed variable effectiveness in the 13-LGS. Here, we sought to examine how the time of year (relative to hibernation emergence) influenced the degree of cone damage in 13-LGS following intravitreal injection of adenosine triphosphate (ATP).

Methods: 
Eighteen (9M,9F) 13-LGS were placed into three active season experimental groups, early-season (N=6), mid-season (N=6), and late-season (N=6), to determine the time of intravitreal ATP injection. Each animal underwent baseline imaging OU using near-infrared reflectance and short wavelength autofluorescence scanning light ophthalmoscopy (SLO) as well as optical coherence tomography (OCT). Animals then received a 10µL intravitreal injection of 0.723M ATP in one eye, followed by OCT and SLO imaging at 1, 3, 10, and 21 days post-injection. Among mid-season and late-season animals where no retinal damage was observed in follow-up imaging, adaptive optics SLO (AOSLO) was performed. Retinal thickness and cone density measures from the late-season cohort were compared to values from a control group of wild-type animals (N=12 eyes, OCT; N=6 eyes, AOSLO).

Results: 
Five animals showed retinal damage following ATP injection, including 4/6 early-season, 0/6 mid-season, & 1/6 late-season (Fisher’s exact test, p= 0.065). A two-way ANOVA showed significant differences in axial length between early-season & mid/late season cohorts (p = 0.029; p = 0.035). All animals with retinal damage displayed lesions on SLO and disrupted retinal lamination on OCT. Follow-up imaging with AOSLO on mid-season and late-season animals without observed retinal damage showed no evidence of photoreceptor disruption at any of the 97 ROIs analyzed. In late-season animals, 518 of 528 eccentricity matched locations imaged by OCT were within the normative range (mean +/- 2SD) from the control group, consistent with no ATP-induced damage.

Conclusions:
The 13-LGS retina may be more susceptible to retinal damage by intravitreal ATP injection during the early season. However, differences in both axial length and vitreous volume between groups may impact the effective dose. Future studies adjusting dose based on ocular biometry may help elucidate the impact of time of year on chemical response.

ATP-induced retinal damage in cone-dominant 13-lined ground squirrel throughout euthermia

Background
Photophobia in the pediatric population is an uncommon complaint in the ophthalmology office, but one that can be debilitating for the patient and a cause of much consternation for the provider. In a prior retrospective review of 36 pediatric patients presenting with a primary complaint of photophobia, 25 of these children (69.4%) left the clinic without a diagnosis.1 In this study, we seek to better understand why so many children leave the office without a specific cause.

Methods
We performed a new retrospective study of patients less than eighteen years old presenting with a primary complaint of photophobia between July 1, 2016 and August 6, 2021. We documented the demographics, pertinent past medical history, diagnoses, and treatments of this population.

Results
Three hundred four pediatric charts from the University of Utah Ophthalmology and Optometry clinics were identified, and one hundred twenty-five unique patients were included for analysis. Migraine headache was the most common identified cause of pediatric photophobia (29.6%) followed by eyelid inflammation/abnormality (7.2%), but frequently a cause is not identified (30.4%). High morbidity and vision threatening conditions including pediatric glaucoma, inherited retinal disease, and intracranial masses were occasionally implicated (3.2%). Treatment is generally symptomatic with tinted lenses (47.2%), but often no treatment is proffered (21.6%) and the patient was simply observed.

Conclusion
Although many neurologists and headache specialists may be aware of the most common causes of photophobia in children and adults, many ophthalmologists remain unaware of these causes. Migraine is the most common cause of photophobia identified (29.6%), but approximately one-third remains without an identifiable cause (30.4%), and the remainder has an alternative identifiable cause (40.0%). Because of this significant knowledge gap, we are developing a curriculum to teach providers how to address photophobia in their patients.

Causes of Photophobia in Children Evaluated at a Tertiary Eye Center

New technology has allowed for infrared imaging of the meibomian glands, but a standardized method of image analysis has not been uniformly adopted. This is a verification study and comparison of two commonly-utilized analysis methods, the Meiboscore method and Line Tracing (LT) method, applied to images taken using the TearScience® LipiView® II Ocular Surface Interferometer (Johnson & Johnson Vision Care, Inc., New Brunswick).

Challenges and drawbacks of meibography analysis: Meiboscore versus Line Tracing method

Comparing FA and OCTA evaluation of retinal vascularity of murine eyes with diabetic retinopathy with Contrast-Limited Adaptive Histogram Equalization (CLAHE) and Matched Filter Image Processing Technique

Background: 
Dry Eye Syndrome (DES) is a multifactorial disorder of the ocular surface, characterized by inadequate moisture and subsequent discomfort, pain, or visual disturbances. DES is associated with increased corneal dendritic cell (DC) density, a marker of inflammation. Treatments proposed to decrease inflammation in DES currently lack quantitative evidence. This study investigated the effects of cyclosporine eye drops on corneal DC density using in vivo confocal microscopy (IVCM). Our hypothesis is that topical cyclosporine treatment will reduce inflammation as demonstrated by decreased DC density.

Methods:
In this prospective study, central cornea images for DES patients were obtained with IVCM (HRT III RCM). Images were taken prior to and three months after treatment with either cyclosporine 0.05% or 0.09% twice daily in both eyes. A semi-automated cell count software was used to analyze dendritic cells (DCs) in the sub-basal nerve plexus. A student t-test was conducted to compare DC density before and after treatment.

Results:
20 eyes of 10 patients (7 women; mean age 56 ± 22 years) completed the study. 16 eyes and 4 eyes were treated with cyclosporine 0.05% and 0.09% respectively. One eye was excluded due to poor image quality. Mean DC density was 64.63 ± 81.48 cells/mm2 at baseline and 50.36 ± 61.86 cells/mm2 after three months of treatment. There was an average DC density decrease of 14.26 ± 44.95 cells/mm2 after treatment. 12 eyes showed decreased corneal DC density and 7 eyes showed either no detectable change or increased DC density. For eyes treated with cyclosporine 0.05% and 0.09%, the mean difference between baseline and post-intervention was a non-statistically significant decrease of 3.00 ± 25.56 cells/mm2 (p=0.92) and 56.50 ± 77.87 cells/mm2 (p=0.24) respectively.

Conclusion: 
Topical cyclosporine is known to be effective in treating DES, but its microstructural effects on ocular surface inflammation have not been quantified. In this study, IVCM was used to quantify cyclosporine’s effects on reducing corneal DC density in dry eyes. Further investigation is necessary to elucidate this potentially dose-related effect.

Effect of Topical Cyclosporine on Dendritic Cell Density in Patients with Dry Eye Syndrome Using In Vivo Confocal Microscopy

Abstract Title: Morphological and Vascular Features of the Optic Nerve in Healthy Asians

Background: Glaucoma is the second leading cause of blindness worldwide, impacting nearly 3 million patients in the US and 80 million globally. Glaucoma is characterized by progressive optic neuropathy, which leads to structural and vascular damage to the optic nerve (ON) and retina. A novel technology, known as optical coherence tomography angiography (OCTA), captures both the structure and vascular features of the retina and ON. Previous studies have indicated that blacks with large optic discs (ODs) experience a more severe form of glaucoma. Information about OD size and glaucoma in Asians is not well documented. Therefore, the aim of our study was to evaluate morphological and vascular features of the OD in healthy South Asian (SA India), East Asian (EA- China), and Southeast Asian (SEA- Vietnam) patients using OCTA scans.

Methods: In this IRB approved, retrospective, age-matched study conducted at an academic center, we reviewed OCTA scans from 76 healthy subjects who were self-identified as SA, SEA, or EA. Exclusion criteria included high myopia/hyperopia, poor scan quality and vitreoretinal disorders. We measured mean disc area, rim area, cup/disc ratio, and vessel densities on the ON. Data was analyzed with pairwise Student’s two-tailed t-tests.

Results: After exclusions, 46 patients [33 (62 eyes) SA, 4 (8 eyes) EA, 9 (16 eyes) SEA] were included. The mean disc vertical size of SEA was higher than SA (1.84mm vs. 1.73mm, p=0.016). The mean disc area in SEA was higher than that in SA (2.49mm² vs. 2.25mm², p=0.024). There were no differences in measurements between SA and EA or EA and SEA. Peripapillary vessel density was significantly higher in SA than in EA (52.2% vs. 50.2%, p=0.036). All other measurements were not significant.

Conclusion: Our pilot study has shown that disc area and disc vertical size are greater in SEA than SA, potentially making them more prone to glaucomatous damage. We believe that these OD ethnic differences, if further investigated, could serve as early markers of glaucoma in healthy Asian eyes.

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