Ocular findings of oral sildenafil use in term and near-term neonates

Kehat, Rinat; Bonsall, Dean J.; North, Robert A.; Connors, Brenda

doi:10.1016/j.jaapos.2009.12.161

Cited by 28 publications

(25 citation statements)

References 18 publications

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“…[57][58][59] Studies of the neonatal population have shown no adverse ocular findings in association with sildenafil. 20 Our results from the sham groups confirm that sildenafil does not affect normal retinal function, as is demonstrated by the absence of a difference in the ERG amplitudes between the sham rat pups treated with different doses of sildenafil and the sham vehicle rat pups. Most importantly, our results from the HI animals suggest that sildenafil limited or repaired the retinal injury resulting from neonatal HI, with a substantial improvement of retinal function and structure compared with the untreated rat pups.…”

Section: Discussionsupporting

confidence: 80%

“…A later study with larger number of newborns reported no adverse ocular findings in association with sildenafil. 20 In fact, one study suggested that vaso-obliteration and neovascularization, which are the hallmarks of retinopathy of prematurity, were decreased after sildenafil administration in a mouse model of retinopathy of prematurity. 31 Thus, we hypothesized that sildenafil may be a therapeutic candidate to treat retinal injury induced by neonatal HI at termequivalent age.…”

mentioning

confidence: 99%

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Sildenafil Improves Functional and Structural Outcome of Retinal Injury Following Term Neonatal Hypoxia-Ischemia

Jung

Johnstone

Khoja

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. The purpose of this study was to investigate the effects of sildenafil on retinal injury following neonatal hypoxia-ischemia (HI) at term-equivalent age in rat pups.METHODS. Hypoxia-ischemia was induced in male Long-Evans rat pups at postnatal day 10 (P10) by a left common carotid ligation followed by a 2-hour exposure to 8% oxygen. Shamoperated rats served as the control group. Both groups were administered vehicle or 2, 10, or 50 mg/kg sildenafil, twice daily for 7 consecutive days. Retinal function was assessed by flash electroretinograms (ERGs) at P29, and retinal structure was assessed by retinal histology at P30.RESULTS. Hypoxia-ischemia caused significant functional (i.e., attenuation of the ERG a-wave and b-wave amplitudes and photopic negative response) and structural (i.e., thinning of the total retina, especially the inner retinal layers) retinal damage in the left eyes (i.e., ipsilateral to the carotid ligation). Treatment with the different doses of sildenafil led to a dose-dependent increase in the amplitudes of the ERG a-and b-waves and of the photopic negative response in HI animals, with higher doses associated with greater effect sizes. Similarly, a dose response was observed in terms of improvements in the retinal layer thicknesses.CONCLUSIONS. Hypoxia-ischemia at term-equivalent age induced functional and structural damage mainly to the inner retina. Treatment with sildenafil provided a dose-dependent recovery of retinal function and structure.

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Section: Discussionsupporting

confidence: 80%

mentioning

confidence: 99%

Sildenafil Improves Functional and Structural Outcome of Retinal Injury Following Term Neonatal Hypoxia-Ischemia

Jung

Johnstone

Khoja

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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“…Studies on the effect of sildenafil on ROP, however, have not found any significant increase in the risk of ROP. The currently available evidence is limited to three reports: a report of a case of an extremely premature newborn who developed severe ROP at 34 weeks’ gestational age while receiving sildenafil; a prospective observational study of term and late preterm infants on more than 2 weeks of sildenafil; and a retrospective case-control study of 17 infants younger than 30 weeks gestation who had received sildenafil during hospitalization (38, 39). In the two latter studies, the investigators did not observe any ocular complications that could be directly linked to the use of sildenafil.…”

Section: Eye Disordersmentioning

confidence: 99%

Safety of Sildenafil in Infants*

Samiee-Zafarghandy

Smith

Anker

2014

Pediatric Critical Care Medicine

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Objective In view of the recent U.S. Food and Drug Administration’s warning against the use of sildenafil in pediatric patients, we aimed to provide an updated overview of the dosing and safety of sildenafil in infants and to explore the relevance of the present safety concerns to the infant population. Data Source The National Library of Medicine PubMed and Cochrane Database of Systematic Reviews were searched using the following terms: Sildenafil AND (infant OR infants OR newborn OR newborns OR child OR children OR childhood OR pediatric OR pediatrics OR paediatric OR paediatrics). Study Selection Studies presenting original clinical data regarding the dosing, use, or safety of sildenafil in infants with pulmonary hypertension would be included. Data Extraction Of the 49 included studies, case reports and case series were the most common type of publications (n = 25). The identified trials included 625 children, with more than 140 infants. Persistent pulmonary hypertension of the newborn and pulmonary hypertension associated with other conditions were the most common underlying diagnoses. Conclusion There is currently no evidence of serious adverse event in infants exposed to sildenafil. Present safety concerns regarding the use of sildenafil in pediatric patients should be further explored before being applied to infant population. Sildenafil remains a valuable option for the treatment of pulmonary hypertension in young infants. Prospective studies should be designed in such a way that they include a safety assessment to evaluate potential adverse outcomes of sildenafil therapy in this population.

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“…52,53 Whereas case reports have linked sildenafil treatment with potentially enhanced ROP progression and severity, 53 subsequent retrospective crosssectional studies have found no adverse outcomes in premature infants with ROP who were treated with sildenafil for pulmonary hypertension. 54,55 Previous studies of the effects of PDE5 inhibitors in the eye have focused largely on retinal and choroidal blood flow, showing increased choroidal congestion and ophthalmic artery velocity and flow, with controversial results in the retinal vasculature. 56,57 Using ex vivo human retinal tissue to study the distribution of PDE5, researchers have shown that in addition to retinal and choroidal vasculature, PDE5 was expressed in retinal ganglion and bipolar cells.…”

Section: Existing Data For Retinal Side Effects Of Sildenafil In Humamentioning

confidence: 99%

Sildenafil Attenuates Vaso-Obliteration and Neovascularization in a Mouse Model of Retinopathy of Prematurity

Fawzi

Chou

Kim

et al. 2014

Invest. Ophthalmol. Vis. Sci.

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Sildenafil treatment significantly decreased retinal vaso-obliteration and neovascularization in a mouse OIR model. These effects are likely due to sildenafil-induced HIF1α stabilization during hyperoxia exposure. Furthermore, we confirm disease overlap by showing that OIR mice also develop hyperoxia-induced right ventricular hypertrophy, which is prevented by sildenafil. This study is a first step toward delineating a potential therapeutic role for sildenafil in OIR and further suggests that there may be common pathophysiologic mechanisms underlying hyperoxia-induced retinal and pulmonary vascular disease.

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Ocular findings of oral sildenafil use in term and near-term neonates

Cited by 28 publications

References 18 publications

Sildenafil Improves Functional and Structural Outcome of Retinal Injury Following Term Neonatal Hypoxia-Ischemia

Sildenafil Improves Functional and Structural Outcome of Retinal Injury Following Term Neonatal Hypoxia-Ischemia

Safety of Sildenafil in Infants*

Sildenafil Attenuates Vaso-Obliteration and Neovascularization in a Mouse Model of Retinopathy of Prematurity

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