(IVB) have been found to be effective for the treatment of retinopathy of prematurity (ROP). However, serum levels of vascular endothelial growth factor (VEGF) have been found to be suppressed for 2 weeks after IVB in patients with ROP. Changes in serum VEGF levels after IVB in patients with ROP may be important because VEGF also plays a role in the neurodevelopment of newborns. OBJECTIVE To investigate the correlation of levels of VEGF and related growth factors with bevacizumab levels in the systemic circulation after IVB in patients with type 1 ROP. DESIGN, SETTING, AND PARTICIPANTS We studied a prospective case series at an institutional referral center from December 1, 2011, through February 28, 2013. We enrolled patients with type 1 ROP who received IVB. We collected blood samples before and for as long as 8 weeks after IVB. The samples were tested for serum levels of bevacizumab and growth factors, including VEGF, VEGF receptor 1 (VEGFR1), VEGFR2, Tie2, erythropoietin, transforming growth factor β1, insulinlike growth factor type 1, angiopoietin 1, angiopoietin 2, angiopoietinlike 3, and angiopoietin 4. The serum concentrations of these factors were measured using enzyme-linked immunosorbent assays. MAIN OUTCOMES AND MEASURES Serum levels of VEGF, bevacizumab, and the other growth factors before and for as long as 8 weeks after IVB. RESULTS We enrolled 8 patients with type 1 ROP. Bevacizumab levels were elevated 1 day after IVB in the 3 patients for whom measurements were available (mean [SD], 1425 [1010 (95% CI, 0-3934)] ng/mL; P = .13) and remained detectable in the serum as long as 8 weeks after IVB (285 ng/mL for the 1 patient with a measurement available). Serum VEGF levels were suppressed for the same period (mean [SD] level at 1 day after IVB, 379 [226 (95% CI, 190-568)] pg/mL for the 3 patients with measurements available; at 8 weeks, 216 pg/mL for the 1 patient with a measurement available). We found a negative correlation between the serum levels of bevacizumab and VEGF in the patients with ROP who received IVB (r = −0.43 [95% CI, −0.67 to −0.10]; P = .01). No changes were identified in the serum levels of any of the other factors after IVB. Bevacizumab may interfere with the actual level of VEGF in the serum, and the total VEGF level in the serum cannot be determined when bevacizumab is present. Wide CIs were noted in the measurement of these factors, probably owing to the small number of patients enrolled in this study. CONCLUSIONS AND RELEVANCE Serum VEGF levels were suppressed for 2 months after IVB in patients with type 1 ROP owing to the leakage of bevacizumab into the systemic circulation.
Connexins (Cx), a large family of membrane proteins, are key components of gap junction channels. These channels are critical intercellular pathways through which ions or small molecules are passed, regulating a variety ofphysiological and developmental processes. One of these processes is hearing. In the current study, a genetic survey was made on 380 Taiwanese individuals, 260 with nonsyndromic deafness and 120 with normal hearing. All the 380 Taiwanese were screened for the presence of mutations in 8 genes of the Cx gene family. These genes included Cx26 (GJB2), Cx29 (GJE1), Cx30 (GJB6), Cx30.3 (GJB4), Cx31 (GJB3), Cx32 (GJB1), Cx43 (GJA1) and pseudogene [ρ] of Cx43 (ρ GJA1). Mutations were identified in 7 out of the 8 screened genes of the Cx family from 62 of the 260 deaf subjects (23.85%). Of the 17 mutations observed in the Cx gene family, 11 were novel mutations. Fourteen polymorphisms that were not associated with hearing loss were identified in the Cx gene family. The first 2 most frequently occurring mutations were found in the Cx26 (28/62; 45.16%) and the ρ Cx43 (17/62; 27.42%), respectively. Nine cases of mutations were found in the Cx30.3 (9/62; 14.52%). In the Cx30, 1 novel mutation was identified in 1 case (1/62; 1.61%). Two patients with mutations of each of Cx29 and Cx43 were found (2/62; 3.23%). One novel mutation of Cx31 was identified in 3 patients with nonsyndromic deafness (3/62; 4.84%). The Cx32 was the only gene without detecting any mutation or polymorphism.Our study provides information for understanding the importance of genetic factors in nonsyndromic deafness of the Taiwanese and may be of use in the improvement of genetic diagnosis of hearing loss in Taiwan.
PurposeThe current study aims to investigate the neurodevelopment of premature infants after intravitreal injections of bevacizumab (IVB) for the treatment of retinopathy of prematurity (ROP) up to the age of 2 years.MethodsThe study design was retrospective observational case series conducted at an institutional referral center. Infants with type 1 ROP were classified into 3 groups: laser only, IVB only, and a combination of IVB and laser treatment. Main Outcome Measures were neurodevelopmental outcomes of the patients after treatment were assessed by Bayley Scales for Infant Development.ResultsSixty-one patients who finished the neurodevelopmental survey were included. No detrimental effects on neurodevelopment were found in IVB group compared with the patients who received laser treatment only. The patients in the IVB + laser group had a higher incidence of significant mental (p = 0.028) and psychomotor (p = 0.002) impairment at 24 months than the patients in the laser group. The odds ratio of having severe psychomotor defects in the IVB + laser group was 5.3 compared with the laser group (p = 0.041). The causal source for the differences that were detected remained unknown due to lack of randomization in the study and accompanying bias in patient selection.ConclusionsTwo years after laser and/or intravitreal injections of bevacizumab for infants with retinopathy of prematurity, no difference on neurodevelopment for those who received only bevacizumab versus only laser treatment were found. Those infants who required rescue therapy with laser or bevacizumab injection after initial, unsuccessful treatment showed some detrimental, neurodevelopmental effects.
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