Multivariate Models to Diagnose Early Referral-Warranted Retinopathy of Prematurity With Handheld Optical Coherence Tomography.

Purpose: The purpose of this study was to create multivariate models predicting early referral-warranted retinopathy of prematurity (ROP) using non-contact handheld spectral-domain optical coherence tomography (OCT) and demographic data. Methods: Between July 2015 and February 2018, infants ≤1500 grams birth weight or ≤30 weeks gestational age from 2 academic neonatal intensive care units were eligible for this study. Infants were excluded if they were too unstable to participate in ophthalmologic examination (2), had inadequate image quality (20), or received prior ROP treatment (2). Multivariate models were created using demographic variables and imaging findings to identify early referral-warranted ROP (referral-warranted ROP and/or pre-plus disease) by routine indirect ophthalmoscopy. Results: A total of 167 imaging sessions of 71 infants (45% male infants, gestational age 28.2+/-2.8 weeks, and birth weight 995.6+/-292.0 grams) were included. Twelve of 71 infants (17%) developed early referral-warranted ROP. The area under the receiver operating characteristic curve (AUC) was 0.94 for the generalized linear mixed model (sensitivity = 95.5% and specificity = 80.7%) and 0.83 for the machine learning model (sensitivity = 91.7% and specificity = 77.8%). The strongest variables in both models were birth weight, image-based Vitreous Opacity Ratio (an estimate of opacity density), vessel elevation, and hyporeflective vessels. A model using only birth weight and gestational age yielded an AUC of 0.68 (sensitivity = 77.3% and specificity = 63.4%), and a model using only imaging biomarkers yielded 0.88 (sensitivity = 81.8% and specificity = 84.8%). Conclusions: A generalized linear mixed model containing handheld OCT biomarkers can identify early referral-warranted ROP. Machine learning produced a less optimal model. Translational Relevance: With further validation, this work may lead to a better-tolerated ROP screening tool.

Early life experience influences dispersal in coyotes (Canis latrans).

Natal dispersal plays an important role in connecting individual animal behavior with ecological processes at all levels of biological organization. As urban environments are rapidly increasing in extent and intensity, understanding how urbanization influences these long distance movements is critical for predicting the persistence of species and communities. There is considerable variation in the movement responses of individuals within a species, some of which is attributed to behavioral plasticity which interacts with experience to produce interindividual differences in behavior. For natal dispersers, much of this experience occurs in the natal home range. Using data collected from VHF collared coyotes (Canis latrans) in the Chicago Metropolitan Area we explored the relationship between early life experience with urbanization and departure, transience, and settlement behavior. Additionally, we looked at how early life experience with urbanization influenced survival to adulthood and the likelihood of experiencing a vehicle related mortality. We found that coyotes with more developed habitat in their natal home range were more likely to disperse and tended to disperse farther than individuals with more natural habitat in their natal home range. Interestingly, our analysis produced mixed results for the relationship between natal habitat and habitat selection during settlement. Finally, we found no evidence that early life experience with urbanization influenced survival to adulthood or the likelihood of experiencing vehicular mortality. Our study provides evidence that early life exposure influences dispersal behavior; however, it remains unclear how these differences ultimately affect fitness.

Dome-shaped macula in premature infants visualized by handheld spectral-domain optical coherence tomography.

PURPOSE: To describe dome-shaped macula and associated clinical findings in premature infants. METHODS: This prospective, observational cohort study included a consecutive sample of premature infants screened for retinopathy of prematurity (ROP) with 9-month follow-up. Handheld spectral domain optical coherence tomography (SD-OCT) was performed at the time of ROP screening. Images were assessed for dome-shaped macula, cystoid macular edema, epiretinal membrane, vitreous bands, and punctate hyperreflective vitreous opacities. Dome height measurements were performed in a subset of images. Teller visual acuity and cycloplegic refraction were performed at an adjusted age of 8-10 months. RESULTS: Of 37 infants (74 eyes; 49% male; mean gestational age 27.8 ± 3.2 weeks; mean birth weight 949 ± 284 g), 24/37 (65%) demonstrated dome-shaped macula in at least one eye (13 both eyes, 5 right eye only, and 6 left eye only). Of the 74 eyes, 26 (35%) could be reliably measured, with a mean dome height of 139.0 ± 72.3 µm (range, 54-369 µm). Presence of dome-shaped macula was associated with a diagnosis of ROP (P = 0.02; OR, 3.03; 95% CI, 1.18-7.82) and pre-plus or plus disease (P = 0.02; OR, 4.20; 95% CI, 1.05-16.78). Infants with dome-shaped macula had lower birth weight compared with those without (877 vs 1081 g; P = 0.04). No associations with other demographics, OCT findings, and 9-month refractive outcomes were found. CONCLUSIONS: Dome-shaped macula was frequently identified by handheld SD-OCT in premature infants, especially those with lower birth weight and severe ROP. The long-term clinical significance of this finding is unknown.

Progression From Soft Lens to Piggyback Soft-Scleral Contact Lens System to Facilitate Scleral Lens Use in a Pediatric Patient.

ABSTRACT: Traumatic injury in the pediatric population often results in significant refractive errors that if left untreated can lead to amblyopia. Scleral contact lenses (ScCLs) have recently gained popularity in this population for efficacy in treatment of significant refractive errors, including irregularity astigmatism and corneal abnormalities. Scleral contact lens intolerance may limit the ability of practitioners to use this modality. Although a soft contact lens (SCL) is generally well tolerated, it cannot treat refractive error as effectively as an ScCL. We recently used an SCL followed by an SCL-ScCL combination ("piggyback" system) sequence in a pediatric patient to facilitate use of an ScCL alone. We hope that our results may provide practitioners with an additional option when treating this challenging patient population.

Surgical outcomes of Glaucoma associated with Axenfeld-Rieger syndrome.

BACKGROUND: The surgical management of glaucoma associated with Axenfeld-Rieger Syndrome (ARS) is poorly described in the literature. The goal of this study is to compare the effectiveness of various glaucoma surgeries on intraocular pressure (IOP) management in ARS. METHODS: Retrospective cohort study at a university hospital-based practice of patients diagnosed with ARS between 1973 and 2018. Exclusion criterion was follow-up less than 1 year. The number of eyes with glaucoma (IOP ≥ 21 mmHg with corneal edema, Haabs striae, optic nerve cupping or buphthalmos) requiring surgery was determined. The success and survival rates of goniotomy, trabeculotomy±trabeculectomy (no antifibrotics), cycloablation, trabeculectomy with anti-fibrotics, and glaucoma drainage device placement were assessed. Success was defined as IOP of 5-20 mmHg and no additional IOP-lowering surgery or visually devastating complications. Kaplan-Meier survival curves and the Wilcoxon test were used for statistical analysis. RESULTS: In 32 patients identified with ARS (median age at presentation 6.9 years, 0-58.7 years; median follow-up 5.4 years, 1.1-43.7 years), 23 (71.9%) patients were diagnosed with glaucoma at median age 6.3 years (0-57.9 years). In glaucomatous eyes (46 eyes), mean IOP at presentation was 21.8 ± 9.3 mmHg (median 20 mmHg, 4-45 mmHg) on 1.0 ± 1.6 glaucoma medications. Thirty-one eyes of 18 patients required glaucoma surgery with 2.2 ± 1.2 IOP-lowering surgeries per eye. Goniotomy (6 eyes) showed 43% success with 4.3 ± 3.9 years of IOP control. Trabeculotomy±trabeculectomy (6 eyes) had 17% success rate with 14.8 ± 12.7 years of IOP control. Trabeculectomy with anti-fibrotics (14 eyes) showed 57% success with 16.5 ± 13.5 years of IOP control. Ahmed© (FP7 or FP8) valve placement (8 eyes) had 25% success rate with 1.7 ± 1.9 years of IOP control. Baerveldt© (250 or 350) device placement (8 eyes) showed 70% success with 1.9 ± 2.3 years of IOP control. Cycloablation (4 eyes) had 33% success rate with 2.7 ± 3.5 years of IOP control. At final follow-up, mean IOP (12.6 ± 3.8 mmHg, median 11.8 mmHg, 7-19 mmHg) in glaucomatous eyes was significantly decreased (p < 0.0001), but there was no difference in number of glaucoma medications (1.6 ± 1.5, p = 0.1). CONCLUSIONS: In our series, greater than 70% of patients with ARS have secondary glaucoma that often requires multiple surgeries. Trabeculectomy with anti-fibrotics and Baerveldt glaucoma drainage devices showed the greatest success in obtaining IOP control.

Vitreous Findings by Handheld Spectral-Domain OCT Correlate with Retinopathy of Prematurity Severity.

PURPOSE: To evaluate the association between retinopathy of prematurity (ROP) and vitreous findings in premature infants detected by handheld spectral-domain (SD) OCT. DESIGN: Prospective, observational cohort study. PARTICIPANTS: Consecutive sample of 92 premature infants requiring ROP screening at 2 academic neonatal intensive care units between July 2015 and March 2018. METHODS: Infants underwent handheld SD OCT at the time of routine ROP examinations. Two masked, trained graders analyzed right-eye vitreoretinal findings, including semiautomated quantification of punctate hyperreflective vitreous opacities within 5 foveal or parafoveal B-scans (vitreous opacity ratio). MAIN OUTCOME MEASURES: Excluding posttreatment data, vitreous findings were compared with clinical ROP diagnoses. RESULTS: Agreement between image graders for all vitreoretinal findings was 91% (κ = 0.86; 95% confidence interval, 0.82-0.90; P < 0.001). Among 92 infants undergoing 280 imaging sessions (52% male; mean gestational age, 28.3 ± 2.8 weeks; mean birthweight, 1014.5 ± 285.0 g), 36 of 92 (39%) demonstrated ROP. Punctate hyperreflective vitreous opacities were identified in 61 of 92 infants (66%). The presence of punctate hyperreflective vitreous opacities at least once was associated with a diagnosis of ROP (62% vs. 29% without opacities; P = 0.003), maximum ROP stage (P = 0.001), preplus or plus disease (24% vs. 5%; P = 0.005), and type 1 disease (14% vs. 2%; P = 0.03). Among 29 infants (45 imaging sessions) with right-eye punctate hyperreflective vitreous opacities, the vitreous opacity ratio from 2 graders (F1 score, 0.82 ± 0.36; Dice coefficient, 0.97 ± 0.04) correlated with ROP stage (P = 0.02). Tractional vitreous bands on imaging correlated with plus disease status (29% vs. 5% without bands; P = 0.05). CONCLUSIONS: Punctate hyperreflective vitreous opacities and tractional vitreous bands predict the presence and severity of ROP. Further studies should explore handheld OCT as a noninvasive ROP screening tool.

Does sexual conflict increase juvenile survival by reducing cannibalism?

To test the hypothesis that male harassment of females reduces adult female time spent on the water foraging (water use), and thus cannibalism by adult females on juveniles, we manipulated heterospecific prey availability, and social context in adult water striders and measured their effects on: 1) cannibalism of juveniles, 2) activity of adults and 3) habitat use of adults and juveniles. Cannibalism rarely occurred with alternative prey present, but was common without alternative prey. Without alternative prey, females cannibalized much more than males, but contrary to predictions, male presence did not reduce cannibalism rates. Male presence decreased female water use; however, this was counteracted by the fact that the lack of alternative prey increased female water use and activity while on the water. Furthermore, in groups of 4 males with 4 females, lack of alternative prey reduced male activity while on the water. Thus the predicted negative effect of sexual conflict on cannibalism was reduced by female and male responses to low food availability. Juveniles increased time off the water when more females or males were more on the water and active. Overall, cannibalism rates depended on alternative prey, male-female social dynamics, female foraging and juvenile refuge use.

Vitreous Bands Identified by Handheld Spectral-Domain Optical Coherence Tomography Among Premature Infants.

Importance: Handheld spectral-domain optical coherence tomography (SD-OCT) can provide insights into the complex interactions occurring at the vitreoretinal interface in retinopathy of prematurity (ROP) to enhance our understanding of ROP pathology. Objective: To characterize vitreous bands in premature infants with use of handheld SD-OCT. Design, Setting, and Participants: Prospective cohort study conducted from July 7, 2015, to February 28, 2017, at 2 university-based neonatal intensive care units. Seventy-three premature infants who required routine ROP screening examination were recruited. Informed consent was obtained from all legal guardians. Trained graders who were masked to the clinical assessment analyzed each SD-OCT scan of the right eye for vitreoretinal findings. A third trained grader mediated disagreements. Main Outcomes and Measures: Associations between the presence of vitreous bands in premature infants with ROP diagnoses and the presence of other vitreoretinal SD-OCT findings were investigated. Results: Of the 73 infants recruited, 6 infants' parents withdrew their children from the study, and 2 infants were too hemodynamically unstable for imaging, leaving a total of 65 participants. Of these, 32 (49%) were female, 36 (55%) were white, 10 (15%) were Hispanic, 3 (5%) were Native American, 4 (6%) were African American, 4 (7%) were Asian/Pacific Islander, and 8 (12%) were other. The mean (SD) gestational age was 28 (2.7) weeks, the mean (SD) birth weight was 997 g (286 g), and the mean (SD) postmenstrual age at imaging was 34 (3) weeks (mean [SD] total of 3 [2] imaging sessions). Comparing the 24 infants (37%) who had a right eye vitreous band at any time with the 41 (63%) who did not, no difference in mean birth weight, gestational age, postmenstrual age at imaging, sex, or race/ethnicity was identified. No associations with ROP stage (eg, in 6 [25%] infants with vitreous bands vs 4 [9.8%] in those without; P = .23), presence of plus disease (2 [8%] vs 2 [5%]; P = .84), or type 1 ROP (3 [12%] vs 3 [7%]; P = .66) were identified. Vitreous bands were associated with epiretinal membrane detected on SD-OCT (P = .001) with an odds ratio of 9.4 (95% CI, 2.8-31.3) in 15 [62%] infants with vitreous bands vs 6 [15%] in those without. Vitreous bands were also associated with cystoid macular edema (in 15 [62%] infants with vitreous bands vs 1 [27%] in those without; P = .005) with an odds ratio of 4.5 (95% CI, 1.5-13.3). Conclusions and Relevance: In this study, the development of vitreous bands was associated with both cystoid macular edema and epiretinal membrane. These findings suggest a tractional pathogenesis to these entities among premature infants. This study did not find a direct association between vitreous bands and severe ROP. Additional study is needed to determine whether vitreous bands represent subclinical hyaloidal organization leading to retinal detachment in advanced ROP.

Bilateral cataract formation via acute spontaneous fracture of the lens following treatment of hyperglycemic hyperosmolar syndrome.

PURPOSE: Acute development of cataracts that may be transient is known to occur during correction of diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome. Nettleship in 1885 was the first to describe the presence of a transient cataract in three diabetic patients that grew worse and eventually cleared with treatment.1 We present a case of irreversible cataracts formed by nuclear fracture of the crystalline lens after hyperglycemia correction, an entity that has not yet been described. OBSERVATIONS: A 67 year-old Caucasian man presented with sudden bilateral vision loss one week after a week-long hospitalization in the intensive care unit for correction of hyperglycemia in the setting of hyperglycemic hyperosmolar syndrome requiring an insulin drip. This was caused by spontaneous fractures of the lens nuclei causing bilateral irreversible cataracts. The patient underwent uncomplicated bilateral cataract extraction resulting in restoration of normal vision. CONCLUSIONS AND IMPORTANCE: Acute transient cataracts that develop during correction of hyperglycemic hyperosmolar syndrome are thought to result from osmotic lens swelling. In this case report, internal fracture of the lens was produced by mechanical forces generated in the process of lens swelling occurring as a consequence of initial hyperglycemia and its subsequent correction. This case represents a rare ocular complication of hyperglycemia correction, and provides new evidence that mechanical forces can be part of diabetic cataractogenesis.

Resident-performed laser peripheral iridotomy in primary angle closure, primary angle closure suspects, and primary angle closure glaucoma.

PURPOSE: To investigate the power use and complication frequency of resident-performed laser peripheral iridotomy (LPI). METHODS: A retrospective analysis of 196 eyes from 103 patients who underwent neodymium: yttrium-aluminum-garnet laser iridotomy performed by resident physicians from January 1, 2010 through April 30, 2015 at a university-based county hospital was done. All patients were treated for primary angle closure, primary angle closure suspects, and primary angle closure glaucoma. Data were collected on pre- and post-laser intraocular pressure (IOP), ethnicity, laser parameters and complications. Mean power use and frequency of complications were evaluated. Complications included elevated post-laser IOP at 30-45 minutes (≥8 mmHg), hyphema, aborted procedures, and lasering non-iris structures. The number of repeated LPI procedures, was also recorded. RESULTS: Mean total power used for all residents was 78.2±68.7 mJ per eye. Power use by first-year trainees was significantly higher than second- and third-year trainees (103.5±75.5 mJ versus 73.7±73.8 mJ and 67.2±56.4 mJ, respectively, p=0.011). Complications included hyphema or microhyphema in 17.9% (35/196), IOP spikes in 5.1% (10/196), aborted procedures in 1.1% (3/196) and lasering non-iris structures in 0.5% (1/196). LPI was repeated in 22.4% of cases (44/196) with higher incidence of repeat LPI among non-Caucasian compared to the Caucasian subjects (p=0.02). Complication rates did not differ with increased training (p=0.16). CONCLUSION: Total power used for LPI decreased with increased resident training, while the complication rate did not differ significantly among resident classes. Complication rates were comparable to rates reported in the literature for attending-performed LPIs.

Rapid Associative Learning and Stable Long-Term Memory in the Squid Euprymna scolopes.

Learning and memory in cephalopod molluscs have received intensive study because of cephalopods' complex behavioral repertoire and relatively accessible nervous systems. While most of this research has been conducted using octopus and cuttlefish species, there has been relatively little work on squid. Euprymna scolopes Berry, 1913, a sepiolid squid, is a promising model for further exploration of cephalopod cognition. These small squid have been studied in detail for their symbiotic relationship with bioluminescent bacteria, and their short generation time and successful captive breeding through multiple generations make them appealing models for neurobiological research. However, little is known about their behavior or cognitive ability. Using the well-established "prawn-in-the-tube" assay of learning and memory, we show that within a single 10-min trial E. scolopes learns to inhibit its predatory behavior, and after three trials it can retain this memory for at least 12 d. Rapid learning and very long-term retention were apparent under two different training schedules. To our knowledge, this study is the first demonstration of learning and memory in this species as well as the first demonstration of associative learning in any squid.