Parafoveal vessel changes in primary open-angle glaucoma and normal-tension glaucoma using optical coherence tomography angiography.

PURPOSE: To evaluate parafoveal and peripapillary perfusion in healthy, glaucoma suspect, normal-tension glaucoma, and primary open-angle glaucoma subjects. PATIENTS AND METHODS: This was a retrospective cross-sectional study with optical coherence tomography angiography imaging with RTVue XR Avanti (Optovue, Inc., Fremont, CA) of 56 eyes (14 healthy, 14 glaucoma suspect, 16 normal-tension glaucoma, and 12 primary open-angle glaucoma) at a tertiary academic referral center. Parafoveal and peripapillary superficial vessel density and parafoveal superficial retinal thickness were the main parameters of interest. Area under receiver operating characteristic curves were calculated. RESULTS: There were significant decreases in parafoveal superficial vessel density in primary open-angle (40.06±4.54%, P<0.001) and normal-tension glaucoma (42.82±5.16%, P=0.010) but not suspect eyes (45.72±4.37%, P=0.916) compared to healthy eyes (48.10±2.82%). Similarly, decreases were observed in parafoveal inner retinal thickness in primary open-angle (83.19±14.29 µm, P<0.001) and normal-tension glaucoma eyes (94.97±12.44 µm, P=0.035), but not suspect eyes (99.93±9.00 µm, P=0.648), compared to healthy controls (107.00±9.55 µm). Only primary open-angle glaucoma eyes displayed significant changes in peripapillary vessel density (37.63±7.19%) compared to healthy controls (49.12±2.80%, P<0.001). Further statistical adjustment for sex and age revealed a significant decrease in parafoveal vessel density in suspects relative to controls (P=0.039). Diagnostic accuracy of parafoveal vessel density was high with an area under the curve of 0.833±0.073 for normal-tension glaucoma and 0.946±0.049 for primary open-angle glaucoma. CONCLUSION: Parafoveal vessel density was significantly reduced in glaucomatous eyes, with good diagnostic accuracy. These findings provide further evidence that these changes may be useful in the diagnosis and monitoring of disease in glaucoma patients.

Sleep and Limb Movement Characteristics of Children With Atopic Dermatitis Coincidentally Undergoing Clinical Polysomnography.

STUDY OBJECTIVES: Atopic dermatitis (AD) is a prevalent, chronic, itchy skin condition. Children undergoing polysomnography (PSG) may coincidentally have AD. Many children with AD have sleep disturbances. Our study aimed to characterize limb movements in children with AD and their effect on sleep. METHODS: A retrospective chart review was conducted for children who underwent comprehensive attended PSG and had AD. PSG sleep parameters were compared to published normative data. A subset of patients with markedly elevated total limb movements was further compared to a matched group of patients with a diagnosis of periodic limb movement disorder (PLMD) and no history of AD. RESULTS: There were 34 children with AD 6.36 ± 3.21 years (mean ± standard deviation), 50% female and with mild to moderate AD. There was increased wake after sleep onset (WASO = 46.0 ± 37.8 minutes), sleep onset latency (46.5 ± 53.0 minutes) and total limb movement index (13.9 ± 7.5 events/h) compared to normative values. Although our cohort was mostly mild AD, 7 of the 34 children with AD (20%) had a total limb movement index during sleep > 15 events/h. Increased total limb movements in PLMD versus patients with AD was most notable during stage N2 sleep (38 ± 17 versus 22 ± 7, P = .01, respectively). CONCLUSIONS: We found altered PSG parameters in children with AD, suggesting that clinicians should consider the diagnosis when affected children undergo PSG. Although our AD cohort was mild, we still determined a need to consider AD when diagnosing PLMD given the presence of elevated total limb movements in children with AD. CITATION: Treister AD, Stefek H, Grimaldi D, Rupani N, Zee P, Yob J, Sheldon S, Fishbein AB. Sleep and limb movement characteristics of children with atopic dermatitis coincidentally undergoing clinical polysomnography. J Clin Sleep Med. 2019;15(8):1107-1113.

Microbiology of Pediatric Orbital Cellulitis and Trends in Methicillin-Resistant Staphylococcus aureus Cases.

We reviewed medical records of children with orbital cellulitis with positive cultures at a tertiary institution from 2005 to 2018 to identify microbiology trends and features associated with methicillin-resistant Staphylococcus aureus (MRSA) cases. Cultures obtained from the orbits (n = 33), sinuses (n = 31), and dural cavities (n = 4) had yields of 66.7%, 61.3%, and 75%, respectively, compared with 17.6% of blood cultures (n = 69). Fifty-five patients had positive culture results. Staphylococcus aureus was the most common pathogen isolated (n = 19), followed by Streptococcus species, most commonly Streptococcus anginosus (n = 8). The most frequently prescribed antibiotic combination regimen was ampicillin-sulbactam followed by amoxicillin-clavulanate. There were 8 cases of MRSA. MRSA was associated with an age of presentation <1 year old (P = .034). Other clinical features were similar between MRSA and non-MRSA cases. In infants and neonates, or those with epidemiologic risk factors, MRSA should also be considered.

Long-term off-label dupilumab in pediatric atopic dermatitis: A case series.

BACKGROUND/OBJECTIVES: Clinical trials of dupilumab have shown efficacy in treating moderate-to-severe atopic dermatitis (AD) in adult patients. While a phase 2 trial of dupilumab has shown efficacy and safety in children, the medication awaits Food and Drug Administration (FDA) approval, and off-label use is limited by dosing currently available to adults. We present this case series to describe the efficacy and safety profile of off-label dupilumab use in six pediatric patients treated by one provider in a private practice. METHODS: We conducted a retrospective chart review of all patients under the age of 18 receiving dupilumab for AD. Two dosing regimens were used as follows: adult dose for patients ≥ 40 kg and half dose for those < 40 kg. We recorded the investigator's global assessment (IGA) and body surface area (BSA) prior to dupilumab initiation and following treatment. All patients were warned of potential side effects including injection site reaction, conjunctivitis, increased risk of infection, and lack of information about use in children. RESULTS: Six pediatric patients were identified with an average age of 10.8 years (range: 7-15). All patients had a decrease in IGA of at least 2 points using biweekly 300 or 150 milligram (mg) doses for an average treatment duration of 8.5 months (range: 6-11). Three patients (50%) had an IGA of 1 after treatment. No side effects were reported. CONCLUSIONS: Dupilumab appears to be an effective treatment for AD in pediatric patients. Optimal dose and delivery have yet to be determined.

Prevalence of Subclinical CNV and Choriocapillaris Nonperfusion in Fellow Eyes of Unilateral Exudative AMD on OCT Angiography.

PURPOSE: To determine the prevalence of subclinical choroidal neovascularization (CNV) in fellow eyes of patients with unilateral exudative age-related macular degeneration (AMD) using optical coherence tomography angiography (OCTA) and to quantify choriocapillaris nonperfusion adjacent to CNV. METHODS: We retrospectively reviewed all patients with AMD who underwent OCTA and identified eyes with unilateral exudative AMD. We determined the presence of subclinical CNV on custom en face macular slabs of the outer retina and choriocapillaris and confirmed on cross-sectional scans. Two graders quantified the percent choriocapillaris area of nonperfusion (PCAN) in the entire choriocapillaris slab as well as in the "halo" zone (200 µm) surrounding subclinical and exudative CNV lesions. RESULTS: Of 140 AMD patients who underwent OCTA, 34 had unilateral exudative AMD, with five of the 34 fellow eyes (14.7%) having subclinical CNV. Compared with PCAN in the entire slab (10.333 ± 4.288%), we found that "halo" PCAN, surrounding CNV, was significantly higher (13.045 ± 5.809%; P < 0.001). Further, there was a trend for higher PCAN in exudative CNV eyes (15.267 ± 7.230%) compared with their fellow subclinical CNV eyes (10.823 ± 3.365%, P = 0.115). CONCLUSIONS: There is a notable prevalence of subclinical CNV in fellow eyes with unilateral exudative CNV, and significantly greater choriocapillaris nonperfusion adjacent to all CNV lesions. We identified a trend for increased choriocapillaris nonperfusion in exudative AMD eyes as compared with their fellow subclinical CNV eyes, which deserves further study. TRANSLATIONAL RELEVANCE: OCTA can be useful in clinical practice to detect subclinical CNV and study choriocapillaris dysfunction.

Risk Factors for Dupilumab-Associated Conjunctivitis in Patients With Atopic Dermatitis.

Importance: Clinical trials of dupilumab for atopic dermatitis (AD) have reported an increased incidence of conjunctivitis in patients who received dupilumab compared with those who received placebo. Objective: To describe the characteristics of patients who develop conjunctivitis secondary to dupilumab treatment for AD. Design, Setting, and Participants: Case series of 12 patients who reported development of conjunctivitis from a cohort of 142 patients treated with dupilumab for AD at a secondary care center from March 14, 2017, to March 29, 2018. Exposures: Patients received a 600-mg injection of dupilumab as a loading dose and a 300-mg injection every 2 weeks thereafter. Main Outcomes and Measures: Primary outcome measures were severity of AD as measured by the Investigator Global Assessment (IGA) score, a 5-point scale from 0 (clear) to 4 (severe), at the time of dupilumab initiation and at conjunctivitis onset. Results: Of the 12 patients included in this series, 7 (58%) were male. The mean (SD) age of patients was 30 (8.1) years at the time conjunctivitis developed. All patients showed improvement of their AD at the time of conjunctivitis diagnosis, with a mean (SD) 1.9 (0.8)-point decrease in IGA score and 47.8% (11.2%) decrease in body surface area affected. Nine of the 12 patients (75%) had severe baseline AD with an IGA score of 4. All patients who discontinued treatment had severe AD at the time of initial dupilumab administration and had at least 1 atopic condition in addition to AD. Conclusions and Relevance: Conjunctivitis that develops after administration of dupilumab to treat AD may be severe enough to necessitate stopping therapy. Severe conjunctivitis was more likely to develop in patients with more severe baseline AD who had a good response to dupilumab and an increased atopic phenotype. Studies are needed to confirm risk factors associated with development of conjunctivitis and to determine effective treatment.

Volume-Rendered Projection-Resolved OCT Angiography: 3D Lesion Complexity Is Associated With Therapy Response in Wet Age-Related Macular Degeneration.

Purpose: To explore whether quantitative three-dimensional (3D) analysis of choroidal neovascularization (CNV) using projection-resolved optical coherence tomography angiography (PR-OCTA) is associated with treatment response in neovascular age-related macular degeneration (nAMD). Methods: Retrospective, cross-sectional study of 51 eyes of 49 patients undergoing individualized anti-VEGF therapy for nAMD. Patients were classified as "good" or "poor" responders, requiring injections at less or more frequently than 6-week intervals, respectively. Cross-sectional PR-OCTA images were used to measure the distance between Bruch's membrane and highest CNV flow signal. The number of flow layers within the CNV and the distance between these flow layers (CNV flow thickness) were also analyzed. Two masked, independent graders measured the PR-OCTA parameters. We used 3D volume-rendered PR-OCTA to confirm the number of CNV flow layers and further evaluate CNV complexity. Results: Poor responders had significantly greater distance between Bruch's membrane and highest CNV flow signal (P < 0.01), greater number of CNV flow layers (P = 0.022), and greater CNV flow thickness (P < 0.01). Volume-rendered PR-OCTA images confirmed the number of CNV flow layers. Conclusions: Cross-sectional and 3D volume-rendered PR-OCTA provides a novel approach for quantifying CNV complexity. Our results suggest that CNV acquiring more complex 3D vascular structure are associated with more frequent long-term anti-VEGF therapy, reflecting a particular pattern of normalization or complex CNV remodeling process that characterizes these less responsive eyes.