SHORT-TERM REACTIVATION OF RETINOPATHY OF PREMATURITY AFTER PRIMARY RANIBIZUMAB TREATMENT.

PURPOSE: Investigate risk factors for short-term reactivation of retinopathy of prematurity (ROP) after intravitreal ranibizumab (IVR) therapy and determine safety and efficacy of repeat injections. METHODS: Retrospective chart review study of patients screened for ROP as inpatients between 2013 and 2023 who received IVR within the UCLA health care system. Primary outcomes were rates and timing of short-term ROP reactivation, defined as repeat worsening of ROP to stage 2 or 3 before 52 weeks postmenstrual age, as well as risk factors for reactivation. Other outcomes included adverse events and rates of reactivation after a second intravitreal injection. RESULTS: Eighty-two eyes of 43 patients received primary IVR 0.25 mg/0.025 cc for type 1 ROP. Thirteen patients (22 eyes) (30.2% of patients, 26.8% of eyes) developed short-term reactivation an average of 7.2 weeks ± 1.7 weeks after treatment. Increased reactivation risk was associated with zone I disease (odds ratio 6.23, 95% CI, 1.35-28.7, P = 0.019), lower postmenstrual age at first injection (odds ratio 1.64, 95% CI, 1.19-2.26; P = 0.003), and lower gestational age at birth (odds ratio 1.80, 95% CI, 1.04-3.13, P = 0.037). Of the 13 patients that received repeat injections, five required laser treatment for a second reactivation (11.6% of patients receiving IVR). No eyes developed retinal vascular occlusion, endophthalmitis, or cataract. CONCLUSION: Repeat injections may be required after primary IVR for aggressive ROP. Repeat IVR treatment for ROP is effective and poses few ophthalmic adverse events, although additional reactivation remains a risk.

The relationship of diabetic retinopathy severity scales with frequency and surface area of diabetic retinopathy lesions.

PURPOSE: To assess the relationship between qualitative diabetic retinopathy (DR) scales with the precise numbers and surface area of DR lesions within the Early Treatment Diabetic Retinopathy Study (ETDRS) standard seven field (S7F) region on ultrawide-field (UWF) color fundus images. METHODS: In this study, we collected UWF images from adult patients with diabetes. Poor-quality images and eyes with any pathology precluding assessment of DR severity were excluded. The DR lesions were manually segmented. DR severity was graded according to the International Clinical Diabetic Retinopathy (ICDR) and AA protocol by two masked graders within the ETDRS S7F. These lesions' numbers and surface area were computed and correlated against the DR scores using the Kruskal-Wallis H test. Cohen's Kappa was performed to determine the agreement between two graders. RESULTS: One thousand five hundred and twenty eyes of 869 patients (294 females, 756 right eyes) with a mean age of 58.7 years were included. 47.4% were graded as no DR, 2.2% as mild non-proliferative DR (NPDR), 24.0% as moderate NPDR, 6.3% as severe NPDR, and 20.1% as proliferative DR (PDR). The area and number of DR lesions generally increased as the ICDR level increased up to severe NPDR, but decreased from severe NPDR to PDR. There was perfect intergrader agreement on the DR severity. CONCLUSION: A quantitative approach reveals that DR lesions' number and area generally correlate with ICDR-based categorical DR severity levels with an increasing trend in the number and area of DR lesions from mild to severe NPDR and a decrease from severe NPDR to PDR.

PRENATAL MATERNAL CHARACTERISTICS ASSOCIATED WITH RETINOPATHY OF PREMATURITY.

PURPOSE: Determine whether prenatal maternal characteristics such as sociodemographic characteristics, comorbidities, or pregnancy complications affect retinopathy of prematurity (ROP) development. METHODS: Medical records of 236 mother-infant dyads from our institution were reviewed, only including dyads in which infants were born at 30 weeks gestational age or earlier. The primary outcome measure was the risk of ROP (defined Stage 1 or greater in either eye) and its association with prenatal maternal variables. RESULTS: Maternal Medicaid insurance, smoking during pregnancy, and chorioamnionitis were associated with an increased risk of ROP. For Medicaid insurance and chorioamnionitis, these risks were not appreciably altered by adjustment for potential confounders. CONCLUSION: These results suggest that several prenatal maternal factors may independently affect the risk of ROP in preterm infants. Validation of our findings could aid in the identification of infants at high risk for ROP based on prenatal clinical features.

A MULTICENTER STUDY OF RETINOPATHY OF PREMATURITY FOLLOW-UP ADHERENCE.

PURPOSE: Characterize clinical and socioeconomic factors that impact follow-up to complete retinal vascularization and subsequent pediatric ophthalmology follow-up in neonates with retinopathy of prematurity. METHODS: Medical records of 402 neonates diagnosed with retinopathy of prematurity from neonatal intensive care units at the University of California, Los Angeles Mattel Children's Hospital and the University of California, Los Angeles Santa Monica Hospital, both academic medical centers, and the Harbor-University of California, Los Angeles Medical Center, a safety-net county hospital, were reviewed. Primary study outcomes were the rate of follow-up to complete retinal vascularization and adequate pediatric ophthalmology follow-up. Secondary outcome was the rate of nonretinal ocular comorbidity. RESULTS: In whole-cohort analysis, 93.6% of neonates were followed to complete retinal vascularization, and 53.5% had adequate pediatric ophthalmology follow-up. Public insurance was associated with lower rates of pediatric ophthalmology follow-up (Odds ratio 0.66, 95% confidence interval 0.45-0.98, P = 0.04). Participants screened at the academic medical center had lower rates of pediatric ophthalmology follow-up compared with the safety-net county hospital (50.7% vs. 63.5%, P = 0.034). In subgroup analysis, academic medical center participants with public insurance were less likely to have pediatric ophthalmology follow-up than safety-net county hospital participants with public insurance (36.5% vs. 63.8%, P < 0.001) or those with private insurance at the academic medical center (36.5% vs. 59.2%, P< 0.001). CONCLUSION: This study identified high follow-up rates to complete retinal vascularization, lower pediatric ophthalmology follow-up rates, and nonretinal ocular comorbidity at all hospitals. Insurance status relative to hospital type was identified as a risk factor for loss to follow-up. This demonstrates a need to further study health care disparities in retinopathy of prematurity infants.

Implementation of Teleretinal Screening Using Optical Coherence Tomography in the Veterans Health Administration.

Background: The Veterans Health Administration (VHA) has an existing teleretinal screening program that uses nonmydriatic fundus photography to screen for diabetic retinopathy in primary care clinics. Concurrently, optical coherence tomography (OCT) has become a routine screening modality in eye clinics for the diagnosis and management of retinal diseases. Introduction: This study aimed to evaluate the first year of a pilot tele-OCT program that used existing resources within the VHA. Without the tele-OCT program, all patients would have been referred to retina clinic for an in-person evaluation. Materials and Methods: This is a retrospective chart review study of patients evaluated by a retina specialist through asynchronous tele-OCT evaluation in 2019. Electronic medical records were used to assess patients' demographic and clinical characteristics, tele-OCT consult results, and patient adherence to tele-OCT follow-up plans. Results: There were 158 tele-OCT consults originating from optometry and nonretinal ophthalmology clinics in 2019. After tele-OCT evaluation, 113 (71.5%) patients were recommended to be monitored in their originating eye clinic, 27 (17.1%) were referred to intravitreal injection clinic, and 12 (7.6%) were referred to retina clinic for in-person evaluation. Patient adherence to tele-OCT follow-up plans was 76.4%. Patients with decreased central vision (p = 0.007) and patients referred to intravitreal injection clinic (p = 0.043) were most adherent to follow-up. Discussion: The tele-OCT program reduced unnecessary in-person clinic visits and enabled more retina clinic availability. Follow-up adherence was greatest among symptomatic patients and those requiring treatment. Conclusions: Tele-OCT can extend tertiary care resources and improve patient care in a large multidisciplinary eye care practice.

Discordant Zika Virus Findings in Twin Pregnancies Complicated by Antenatal Zika Virus Exposure: A Prospective Cohort.

BACKGROUND: There are limited data on the natural history of antenatal Zika virus (ZIKV) exposure in twin pregnancies, especially regarding intertwin concordance of prenatal, placental, and infant outcomes. METHODS: This prospective cohort study included twin pregnancies referred to a single institution from September 2015 to June 2016 with maternal ZIKV. Polymerase chain reaction (PCR) testing of maternal, placental, and neonatal samples was performed. Prenatal ultrasounds were completed for each twin, and histomorphologic analysis was performed for each placenta. Abnormal neonatal outcome was defined as abnormal exam and/or abnormal imaging. Two- to three-year follow-up of infants included physical exams, neuroimaging, and Bayley-III developmental assessment. RESULTS: Among 244 pregnancies, 4 twin gestations without coinfection were identified. Zika virus infection occurred at 16-33 weeks gestation. Zika virus PCR testing revealed discordance between dichorionic twins, between placentas in a dichorionic pair, between portions of a monochorionic placenta, and between a neonate and its associated placenta. Of the 8 infants, 3 (38%) had an abnormal neonatal outcome. Of 6 infants with long-term follow-up, 3 (50%) have demonstrated ZIKV-related abnormalities. CONCLUSIONS: Neonatal PCR testing, placental findings, and infant outcomes can be discordant between co-twins with antenatal ZIKV exposure. These findings demonstrate that each twin should be evaluated independently for vertical transmission.

Early Clinical Infancy Outcomes for Microcephaly and/or Small for Gestational Age Zika-Exposed Infants.

BACKGROUND: Zika-exposed infants with microcephaly (proportional or disproportional) and those who are small for gestational age without microcephaly should be closely followed, particularly their growth trajectories. They are at high risk of adverse outcomes in the first year of life.Antenatal Zika virus (ZIKV) exposure may lead to adverse infant outcomes including microcephaly and being small for gestational age (SGA). ZIKV-exposed infants with a diagnosis of microcephaly (proportional [PM] or disproportional [DM]) or SGA at birth were evaluated with anthropometric measurements and health outcomes. METHODS: Infants had laboratory-confirmed ZIKV exposure in Brazil. PM, DM, or SGA classification was based on head circumference and weight. First-year growth parameters and clinical outcomes were recorded with analyses performed. RESULTS: Among the 156 ZIKV-exposed infants, 14 (9.0%) were SGA, 13 (8.3%) PM, 13 (8.3%) DM, and 116 (74.4%) were neither SGA nor had microcephaly (NSNM). High rates of any neurologic, ophthalmologic, and hearing abnormalities were observed for PM (100%), DM (100%), and SGA (42.9%) vs NSNM infants (18.3%; P <.001); odds ratio [OR], 3.4 (95% confidence interval [CI], 1.1-10.7) for SGA vs NSNM. Neuroimaging abnormalities were seen in 100% of PM and DM and in 42.9% of SGA vs NSNM infants 16%; (P <.001); OR 3.9 (95% CI, 1.2-12.8) for SGA vs NSNM. Growth rates by z score, particularly for microcephaly infants, were poor after birth but showed improvement beyond 4 months of life. CONCLUSIONS: ZIKV-exposed infants with microcephaly (PM and DM) had similarly high rates of adverse outcomes but showed improvement in growth measurements beyond 4 months of life. While SGA infants had fewer adverse outcomes compared with microcephaly infants, notable adverse outcomes were observed in some; their odds of having adverse outcomes were 3 to 4 times greater compared to NSNM infants.Zika-exposed infants with microcephaly, irrespective of being proportional or disproportional, and those who are small for gestational age without microcephaly should be closely followed, particularly their growth trajectories. They are at high risk of adverse outcomes in the first year of life.

The Role of Amniocentesis in the Diagnosis of Congenital Zika Syndrome.

There are limited data on amniocentesis as a diagnostic tool for congenital Zika syndrome. Here we report on a prospective cohort of 16 women with suspected Zika virus infection in a highly endemic area, and discuss the role of amniocentesis in the prenatal diagnosis of fetal Zika infection.

Relationship between Retinal Thickness Profiles and Visual Outcomes in Young Adults Born Extremely Preterm: The EPICure@19 Study.

PURPOSE: To quantify inner and outer retinal layer thicknesses and understand their relevance to visual function among young adults born extremely preterm (EP). DESIGN: Prospective observational study with 19 years of follow-up. PARTICIPANTS: A total of 354 eyes (226 eyes of former EP infants and 128 age-matched full-term control eyes) from 177 young adults were evaluated. Among EP participants, 50% of eyes (112/226) were not previously diagnosed with neonatal retinopathy of prematurity (ROP), 38% of eyes (84) had ROP not deemed to require treatment in the neonatal period, and 13% of eyes (30) had neonatal cryotherapy or laser ablation for ROP. METHODS: Subjects underwent eye examinations including best-corrected visual acuity (BCVA) and Heidelberg Spectralis (Heidelberg Engineering, Heidelberg, Germany) macular spectral-domain (SD) OCT imaging. Retinal layers were auto-segmented and thickness profiles were computed at the fovea by the instrument software. MAIN OUTCOME MEASURES: Correlation between retinal sublayer thickness and BCVA. RESULTS: Compared with control eyes, the inner and outer retinal layers of EP eyes were significantly thicker and BCVA was significantly reduced. Retinal layer thicknesses and BCVA were similar for untreated EP eyes and those without neonatal ROP. In contrast, treated eyes had increased inner and outer retinal layer thickness and decreased vision. Inner retinal layer thickness was moderately correlated with worse BCVA (r = 0.30, P < 0.001), but outer retinal layer thickness was not (r = -0.01, P = 0.80). Multivariate regression indicated ganglion cell layer thickness was a significant independent predictor of BCVA. CONCLUSIONS: Extremely premature birth influences maturation of the fovea and visual outcomes into early adult life. Increased ganglion cell layer thickness was associated with worse BCVA. Eyes requiring neonatal treatment for ROP had associated worse BCVA at the age of 19 years.

VISUAL FUNCTION AND OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FEATURES IN CHILDREN BORN PRETERM.

PURPOSE: Preterm children have an increased risk of impaired vision from retinopathy, strabismus, and high refractive error. The aim of this study was to investigate the relationship between foveal parameters generated by optical coherence tomography angiography and visual function in preterm children. METHODS: Eighty eyes (32 eyes of former preterm infants and 48 age-matched full-term control eyes) were analyzed. Subjects underwent complete eye examinations including best-corrected visual acuity and retinal imaging with the Optovue XR Avanti optical coherence tomography angiography device. Foveal morphologic parameters including foveal depth, central foveal thickness, inner retinal area, and outer retinal area were measured on a central horizontal B-scan. Foveal vasculature parameters including foveal avascular zone, superficial capillary plexus-vessel density, and deep capillary plexus-vessel density were measured on optical coherence tomography angiography. RESULTS: The best-corrected visual acuity was significantly affected in preterm children compared with controls (P < 0.0001). The central foveal thickness (P < 0.0001), inner retinal area (P = 0.01), and outer retinal area (P = 0.03) were significantly increased in preterm compared with control eyes. Foveal depth (P < 0.001) and foveal avascular zone (P < 0.001) were significantly decreased in preterm compared with control eyes. The superficial capillary plexus-vessel density (P = 0.01) and deep capillary plexus-vessel density (P = 0.003) at the fovea (1 mm) were significantly increased in preterm compared with control eyes. The best-corrected visual acuity was negatively correlated with foveal depth (r = -0.42, P = 0.001) and foveal avascular zone (r = -0.53, P < 0.001), and positively correlated with central foveal thickness (r = 0.32, P = 0.01) and inner retinal area (r = 0.32, P = 0.01), indicating that worse visual acuity was associated with a smaller foveal avascular zone, shallower foveal depth, increased central foveal thickness, and larger inner retinal area. CONCLUSION: Foveal morphology and vasculature changes in preterm children were associated with impaired visual function. Further longitudinal studies are required to evaluate these changes over time.

MACULAR MICROVASCULAR NETWORKS IN HEALTHY PEDIATRIC SUBJECTS.

PURPOSE: To report optical coherence tomography angiography (OCTA) values in healthy pediatric eyes and to identify factors that may modify these values. METHODS: In this prospective observational cross-sectional study, macular OCTA images were acquired from healthy pediatric patients. Main outcome measures were 1) foveal avascular zone (FAZ) area at the level of the superficial retinal capillary plexus (SCP); 2) SCP and deep retinal capillary plexus (DCP) perfusion density (based on the area of vessels); 3) SCP and DCP vessel density (based on a map with vessels of 1-pixel width); and 4) CC perfusion density. Multiple regression analysis was performed to assess the effect of age, sex, ethnicity, refraction, and foveal macular thickness (FMT) on OCTA parameters. RESULTS: Seventy-seven eyes from 52 subjects (23 male and 29 female) were included in analysis. Mean age was 11.1 ± 3.3 years (range = 5.0-17.0 years). Twenty-nine (55.8%) subjects were white, 14 (27.0%) Hispanic, 8 (15.4%) Asian, and 1 (1.8%) African-American. Mean refraction was -0.1 ± 2.4 diopters (D) (range = -5.75 to +9.0 D). Mean FMT was 248.6 ± 18.6 µm. Larger FAZ area was significantly associated with older age (P = 0.014). Furthermore, larger FAZ area was associated with reduced FMT (P < 0.0001). Male sex was associated only with increased SCP perfusion density (P = 0.042). Increased CC perfusion density was associated with younger age (P = 0.022). CONCLUSION: We report data for pediatric OCTA parameters in healthy subjects. Several variables influence the density of macular microvascular networks, and these factors should be considered in the OCTA study of pediatric eye disorders.

Gender-based differences in letters of recommendation written for ophthalmology residency applicants.

BACKGROUND: To determine whether gender-based differences may be present in letters of recommendation written for ophthalmology residency applicants. METHODS: All applications submitted through SF Match to the UCLA Stein Eye Institute Residency Training Program from the 2017-2018 application cycle were analyzed using validated text analysis software (Linguistic Inquiry and Word Count (Austin, TX)). The main outcome measures were differences in language use in letters of recommendation by gender of applicant. RESULTS: Of 440 applicants, 254 (58%) were male and 186 (42%) were female. The two gender groups had similar United States Medical Licensing Exam (USMLE) Step 1 scores, undergraduate grade point averages (uGPA's), proportions of underrepresented minority (URM) applicants and Gold Humanism Honor Society members, numbers of academic and service activities listed, and gender distributions of their letter writers (all P values > 0.05). However, letters written for male applicants were determined to use more "authentic" words than those written for female applicants (mean difference, 0.800; 95% CI, 0.001-1.590; P = 0.047). Letters written for male applicants also contained more "leisure" words (mean difference, 0.056; 95% CI, 0.008-0.104; P = 0.023) and fewer "feel" words (mean difference, 0.033; 95% CI, 0.001-0.065; P = 0.041) and "biological processes" words (mean difference, 0.157; 95% CI, 0.017-0.297; P = 0.028). CONCLUSIONS: There were gender differences detected in recommendation letters in ophthalmology consistent with prior studies from other fields. Awareness of these differences may improve residency selection processes.

ULTRAWIDEFIELD AUTOFLUORESENCE IN ABCA4 STARGARDT DISEASE.

PURPOSE: To report the ultrawidefield fundus autofluorescence (UWF-FAF) patterns in ABC4A Stargardt disease. METHODS: A retrospective cohort study of patients with a clinical diagnosis of Stargardt disease, confirmed ABCA4 genotype, and ultrawidefield fundus autofluorescence imaging using an Optos P200Tx. Four independent graders evaluated the images. Ultrawidefield fundus autofluorescence images were evaluated for the presence of posterior pole and peripheral findings, and were classified into one of three types (Type I: lesions confined to the macula with no peripheral findings; Type II: macular atrophy with flecks only in the periphery; Type III: macular atrophy and varying degrees of peripheral atrophy). RESULTS: Ultrawidefield fundus autofluorescence was performed on 58 eyes of 29 patients. Reviews of images revealed the presence of peripheral (outside the 55° view of standard nonwidefield FAF imaging) alterations on UWF-FAF in 76% of eyes. Overall, the UWF-FAF pattern was classified as Type I in 24% eyes (14/58), Type II in 24% (14/58), and Type III in 52% (30/58). The most common genetic mutations were c.2588G>C (6/29 patients, 20.7%), and c.5882G>A (5/29 patients, 17.2%). CONCLUSION: Ultrawidefield fundus autofluorescence reveals peripheral changes in the majority of patients with Stargardt disease. Peripheral FAF changes may have implications for diagnosis, prognosis, and management of individual patients with Stargardt disease.

ISCHEMIC CENTRAL RETINAL VEIN OCCLUSION IN THE ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR ERA.

PURPOSE: Anti-vascular endothelial growth factor therapy has improved the prognosis for patients with central retinal vein occlusion (CRVO). However, most studies published to date exclude ischemic CRVO. The purpose of this study was to describe the outcome in eyes with ischemic CRVO treated with anti-vascular endothelial growth factor therapy. METHODS: Thirty-seven patients with ischemic CRVO from 3 centers were followed for at least 6 months. Data on patient demographic, vision status, and anti-vascular endothelial growth factor treatments were collected. RESULTS: Average number of injections during the study period was 5. Younger age was associated with improved vision (P = 0.006). Patients with improved visual outcomes tended to have macular edema as the primary indication for treatment, whereas patients with worse outcomes tended to have neovascularization as the primary indication for treatment. CONCLUSION: This study highlights significant variability in the use of anti-vascular endothelial growth factor therapy for ischemic CRVO and underscores that eyes with neovascularization tend to have worse visual outcomes.

A Practical Approach to Retinal Dystrophies.

Genomic approaches to developing new diagnostic and therapeutic strategies in retinal dystrophies are among the most advanced applications of genetics (Tsang SH, Gouras P (1996) Molecular physiology and pathology of the retina. In: Duane TD, Tasman W, Jaeger AE (eds) Duane's clinical opthalmology. Lippincott-Raven, Philadelphia). The notion that "nothing can be done" for patients with retinal dystrophies is no longer true. Electrophysiological testing and autofluorescence imaging help to diagnose and predict the patient's course of disease. Better phenotyping can contribute to better-directed, cost-efficient genotyping. Combining fundoscopy, autofluorescent imaging, and electrophysiological testing is essential in approaching patients with retinal dystrophies. Emerging are new gene-based treatments for these devastating conditions.

Effects of Myo-inositol on Type 1 Retinopathy of Prematurity Among Preterm Infants <28 Weeks' Gestational Age: A Randomized Clinical Trial.

Importance: Previous studies of myo-inositol in preterm infants with respiratory distress found reduced severity of retinopathy of prematurity (ROP) and less frequent ROP, death, and intraventricular hemorrhage. However, no large trials have tested its efficacy or safety. Objective: To test the adverse events and efficacy of myo-inositol to reduce type 1 ROP among infants younger than 28 weeks' gestational age. Design, Setting, and Participants: Randomized clinical trial included 638 infants younger than 28 weeks' gestational age enrolled from 18 neonatal intensive care centers throughout the United States from April 17, 2014, to September 4, 2015; final date of follow-up was February 12, 2016. The planned enrollment of 1760 participants would permit detection of an absolute reduction in death or type 1 ROP of 7% with 90% power. The trial was terminated early due to a statistically significantly higher mortality rate in the myo-inositol group. Interventions: A 40-mg/kg dose of myo-inositol was given every 12 hours (initially intravenously, then enterally when feeding; n = 317) or placebo (n = 321) for up to 10 weeks. Main Outcomes and Measures: Type 1 ROP or death before determination of ROP outcome was designated as unfavorable. The designated favorable outcome was survival without type 1 ROP. Results: Among 638 infants (mean, 26 weeks' gestational age; 50% male), 632 (99%) received the trial drug or placebo and 589 (92%) had a study outcome. Death or type 1 ROP occurred more often in the myo-inositol group vs the placebo group (29% vs 21%, respectively; adjusted risk difference, 7% [95% CI, 0%-13%]; adjusted relative risk, 1.41 [95% CI, 1.08-1.83], P = .01). All-cause death before 55 weeks' postmenstrual age occurred in 18% of the myo-inositol group and in 11% of the placebo group (adjusted risk difference, 6% [95% CI, 0%-11%]; adjusted relative risk, 1.66 [95% CI, 1.14-2.43], P = .007). The most common serious adverse events up to 7 days of receiving the ending dose were necrotizing enterocolitis (6% for myo-inositol vs 4% for placebo), poor perfusion or hypotension (7% vs 4%, respectively), intraventricular hemorrhage (10% vs 9%), systemic infection (16% vs 11%), and respiratory distress (15% vs 13%). Conclusions and Relevance: Among premature infants younger than 28 weeks' gestational age, treatment with myo-inositol for up to 10 weeks did not reduce the risk of type 1 ROP or death vs placebo. These findings do not support the use of myo-inositol among premature infants; however, the early termination of the trial limits definitive conclusions.

Maternal Zika Virus Disease Severity, Virus Load, Prior Dengue Antibodies, and Their Relationship to Birth Outcomes.

BACKGROUND: Congenital Zika virus (ZIKV) syndrome is a newly identified condition resulting from infection during pregnancy. We analyzed outcome data from a mother-infant cohort in Rio de Janeiro in order to assess whether clinical severity of maternal ZIKV infection was associated with maternal virus load, prior dengue antibodies, or abnormal pregnancy/infant outcomes. METHODS: A clinical severity assessment tool was developed based on duration of fever, severity of rash, multisystem involvement, and duration of symptoms during ZIKV infection. ZIKV-RNA load was quantified by polymerase chain reaction (PCR) cycles in blood/ urine. Dengue immunoglobulin G (IgG) antibodies were measured at baseline. Adverse outcomes were defined as fetal loss or a live infant with grossly abnormal clinical or brain imaging findings. Regression models were used to study potential associations. RESULTS: 131 ZIKV-PCR positive pregnant women were scored for clinical disease severity, 6 (4.6%) had mild disease, 98 (74.8%) had moderate disease, and 27 (20.6%) severe manifestations of ZIKV infection. There were 58 (46.4%) abnormal outcomes with 9 fetal losses (7.2%) in 125 pregnancies. No associations were found between: disease severity and abnormal outcomes (P = .961; odds ratio [OR]: 1.00; 95% confidence interval [CI]: 0.796-1.270); disease severity and viral load (P = .994); viral load and adverse outcomes (P = .667; OR: 1.02; 95% CI: 0.922-1.135); or existence of prior dengue antibodies (88% subjects) with severity score, ZIKV-RNA load or adverse outcomes (P = .667; OR: 0.78; 95% CI: 0.255-2.397). CONCLUSIONS: Congenital ZIKV syndrome does not appear to be associated with maternal disease severity, ZIKV-RNA load at time of infection or existence of prior dengue antibodies.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF THE FOVEA IN CHILDREN BORN PRETERM.

PURPOSE: To compare the foveal avascular zone (FAZ) area measured by optical coherence tomography angiography in children who had been born preterm with age-matched controls. METHODS: In this cross-sectional observational comparative case series, 43 eyes of 26 children (28 eyes of 15 former preterm infants and 15 eyes of 11 former term infants) between the ages of 4 and 12 years old were included. Optical coherence tomography angiography with a scan size of 3 × 3 was performed for all eyes. Foveal avascular zone area was measured using the Optovue RTVue AVANTI instrument (Optovue Inc, Fremont, CA) software. Inner and outer retinal thicknesses were measured with the instrument caliper. RESULTS: A distinct FAZ was absent in 12 eyes (42.8%) of children with a history of preterm birth, however, it was present in all (100%) control eyes. The FAZ area was significantly correlated with gestational age (r = 0.82, P < 0.001) and birth weight (r = 0.80, P < 0.001). The gestational age was less than 29 weeks and birth weight was less than 1,480 grams in eyes with no distinct FAZ. Mean central foveal vessel density in the superficial capillary plexus was 41.8 ± 4.4% in the preterm group and 32.8 ± 5.8% in the control group (P < 0.001). In all eyes, a significant negative correlation was found between the central foveal vessel density and gestational age (r = -0.63, P = 0.001) and birth weight (r = -0.59, P = 0.002). On spectral domain optical coherence tomography examination, the foveal depression was absent and the inner retinal layers were preserved in all eyes with absent FAZ. In all eyes, a significant negative correlation was found between the inner retinal thickness and gestational age (r = -0.68, P < 0.001) and birth weight (r = -0.61, P = 0.001). Ten eyes of 6 preterm children had a history of laser therapy for retinopathy of prematurity. A distinct FAZ was absent in six eyes (60%) with retinopathy of prematurity with history of laser therapy, and six eyes (33.3%) with preterm birth without laser therapy. Eyes with history of laser therapy had a statistically significantly higher inner retinal thickness and central foveal vessel density and smaller FAZ compared with the eyes with preterm birth without laser therapy (P < 0.001, P = 0.04 and P = 0.03, respectively). CONCLUSION: Optical coherence tomography angiography is a novel modality for noninvasive visualization of the retinal vasculature in pediatric patients and expands our knowledge of foveal abnormalities in retinopathy of prematurity. A small or absent FAZ seems to be a distinct sign of prematurity.