sildenafil-citrate and Retinopathy-of-Prematurity

To determine the risk of ocular complications of sildenafil therapy in neonates.. Retrospective case review of neonates with persistent pulmonary hypertension of the newborn who received sildenafil therapy between 2010 and 2015 in a single, tertiary surgical neonatal intensive care unit in Australia. Ophthalmic examination findings in the neonatal intensive care unit and follow-up were examined.. Twenty-seven neonates with persistent pulmonary hypertension of the newborn received sildenafil. The median gestational age (GA) was 38 weeks (range 24-41 weeks), and median birthweight was 2690 g (range 454-4270 g). Ophthalmic review was undertaken in 23 neonates, and 16 neonates were term or near-term infants (GA 31-40 weeks). All of them had a normal initial ophthalmic examination; one child was later diagnosed with hypermetropia and another with infantile esotropia. Amongst the seven premature infants (GA 24-30 weeks), three had retinopathy of prematurity (ROP) diagnosed at the first ophthalmic review and the other four had normal initial examinations. Two patients later developed ROP, one of whom was also diagnosed with congenital motor nystagmus. All five patients diagnosed with ROP were extremely preterm (<28 weeks) with low birthweight (454-635 g).. There were no short-term complications attributable to sildenafil therapy identified in term or near-term neonates (GA ≥31 weeks). This cohort of neonates does not typically undergo ophthalmic review as part of the ROP screening protocol in our institution. Routine ophthalmic review of neonates on sildenafil therapy, who are not at risk of ROP, is therefore unlikely to be warranted. Further research is required to clarify the relationship between sildenafil and ROP.

Topics: Australia; Gestational Age; Humans; Infant; Infant, Newborn; Retinopathy of Prematurity; Retrospective Studies; Risk Factors; Sildenafil Citrate

To assess whether sildenafil is associated with worsening retinopathy of prematurity (ROP) in very low birth weight (VLBW) infants (≤1500 g) with bronchopulmonary dysplasia (BPD).. This retrospective case-control study included VLBW infants admitted to the neonatal intensive care unit between January 1, 2006, and December 31, 2012. Each infant treated with sildenafil was assigned 3 unexposed controls matched for gestational age, birth weight, and BPD diagnosis. Severe ROP was defined as stage ≥3 ROP. Worsening ROP was defined as increased stage of ROP within 8 weeks + 4 days after initiation of sildenafil or matched postmenstrual age.. Twenty-three exposed infants and 69 matched controls met the inclusion criteria for the study (mean birth weight, 715 ± 210 g; mean gestational age, 25 ± 1 weeks). The mean postmenstrual age at sildenafil treatment was 42 ± 8 weeks. Exposed infants had more days of respiratory support (mean, 208 ± 101 days vs 102 ± 33 days; P < .001). Exposed infants had a higher prevalence of severe ROP (26% [6 of 23] vs 7% [5 of 69]; OR, 6.4; 95% CI, 1.2-32.9; P = .026). Five exposed infants and 2 unexposed infants had severe ROP before starting sildenafil and were excluded from the analysis for worsening ROP. The rate of worsening ROP did not differ significantly between exposed infants and unexposed infants ((41% [7 of 17] vs 24% [12 of 51]; OR, 8.4; 95% CI, 0.9-78.6; P = .061).. Although sildenafil treatment was not statistically significantly associated with worsening of ROP, the raw difference in ROP rate is concerning. Larger studies are warranted to confirm this finding.

Topics: Bronchopulmonary Dysplasia; Case-Control Studies; Disease Progression; Dose-Response Relationship, Drug; Female; Gestational Age; Humans; Infant, Newborn; Infant, Very Low Birth Weight; Intensive Care Units, Neonatal; Male; Phosphodiesterase 5 Inhibitors; Retinopathy of Prematurity; Retrospective Studies; Sildenafil Citrate; Treatment Outcome; Visual Acuity

Topics: Female; Humans; Infant, Newborn; Infant, Premature; Retinopathy of Prematurity; Sildenafil Citrate; Vasodilator Agents

To examine the effect of sildenafil therapy on development of severe retinopathy of prematurity (ROP) requiring surgical intervention in premature infants.. We identified premature infants who were discharged from Pediatrix Medical Group neonatal intensive care units from 2003 to 2012 and who received an ophthalmologic exam. We matched each infant exposed to sildenafil before first eye exam to three nonexposed infants using propensity scoring to control for differences in baseline infant characteristics. We evaluated the association between sildenafil exposure and development of severe ROP using conditional logistic regression.. Of the 57 815 infants meeting inclusion criteria, 88 were exposed to sildenafil. We matched 81/88 (92%) sildenafil-exposed with 243 nonexposed infants. There was no difference in the proportion of infants who developed severe ROP in the sildenafil-exposed vs nonexposed groups (17/81 (21%) vs 38/243 (16%), P=0.27). On adjusted analysis, there was no difference in severe ROP in the sildenafil-exposed vs nonexposed infants (odds ratio=1.46, 95% confidence interval=0.76 to 2.82, P=0.26).. We did not observe an association between risk of severe ROP and sildenafil exposure before first eye exam in this cohort of premature infants.

Topics: Bronchopulmonary Dysplasia; Diagnostic Techniques, Ophthalmological; Female; Gestational Age; Humans; Hypertension, Pulmonary; Infant; Infant, Premature; Infant, Very Low Birth Weight; Male; Medical Records, Problem-Oriented; Retinopathy of Prematurity; Risk Assessment; Risk Factors; Sildenafil Citrate; Statistics as Topic; United States; Vasodilator Agents

Systemic diseases and their treatment influence aggressive posterior retinopathy of prematurity.. A premature infant with aggressive posterior retinopathy of prematurity underwent laser treatment with a favourable outcome. She was started on oral sidenafil citrate for pulmonary hypertension. Ten days later she developed neovascularization within the lasered retina.. Considering the possible role of sildenafil in this unusual development, the drug was withdrawn resulting in regression of the neovascularization.. The clinician should be aware of this retinal adverse effect of sildanefil in neonates with aggressive posterior retinopathy of prematurity.

Topics: Female; Humans; Infant, Newborn; Infant, Premature; Light Coagulation; Low-Level Light Therapy; Retinopathy of Prematurity; Sildenafil Citrate; Vasodilator Agents

We sought to determine the effect of sildenafil on retinal vascular changes in a mouse model of oxygen-induced retinopathy (OIR).. Vascular defects in OIR mice were quantified by measuring vaso-obliteration at postnatal days 12 and 17 (P12 and P17) and neovascularization at P17 to compare sildenafil-treated to dextrose-treated OIR mice. Retinal HIF1α protein expression was quantified by Western blotting and normalized to that of β-actin. Right ventricular hypertrophy was measured by Fulton's index as a surrogate for hyperoxia-induced pulmonary hypertension.. At P12, OIR mice treated with sildenafil demonstrated a 24% reduction in vaso-obliteration (P < 0.05), whereas at P17, treated animals showed a 50% reduction in neovascularization (P < 0.05) compared to dextrose-treated controls. Sildenafil-treated OIR mice had stabilization of retinal HIF1α at P12, immediately after hyperoxia. At P17, sildenafil-treated OIR mice had decreased HIF1α relative to untreated mice. OIR mice developed right ventricle hypertrophy that was significant compared to that in room air controls, which was abrogated by sildenafil.. 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.

Topics: Animals; Disease Models, Animal; Mice; Mice, Inbred C57BL; Piperazines; Purines; Retinal Neovascularization; Retinal Vessels; Retinopathy of Prematurity; Sildenafil Citrate; Sulfones; Vasoconstriction; Vasodilator Agents

Sildenafil is occasionally used as rescue treatment for preterm infants with severe bronchopulmonary dysplasia and pulmonary arterial hypertension. In adults, sildenafil treatment has been associated with several ophthalmological adverse effects, including nonarteritic ischaemic optic neuropathy. We reviewed the effect of sildenafil on retinopathy of prematurity (ROP) in very preterm infants.. Retrospective case-control study. Infants born <30 weeks gestation who had received sildenafil during their hospitalisation were included. A control group matched for gestation, birth weight, gender, and place of birth was identified from the departmental database. For every sildenafil case, three matched controls were studied. Baseline data, sildenafil therapy data, results of eye examinations and respiratory data were analysed.. 17 infants received sildenafil between 2004 and 2010. The median duration of sildenafil treatment was 52 days. Baseline characteristics were similar between groups. The odds ratio for an increase in ROP stage in the group treated with sildenafil was 1.35 (95% confidence interval 0.39-4.62, P-value 0.63). One infant in each group required laser treatment.. Sildenafil treatment did not affect ROP progression or increase the need for laser treatment in this cohort.

Topics: Bronchopulmonary Dysplasia; Case-Control Studies; Disease Progression; Humans; Infant, Newborn; Infant, Premature; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Retinopathy of Prematurity; Sildenafil Citrate; Sulfones

Topics: Humans; Hypertension, Pulmonary; Infant, Newborn; Piperazines; Purines; Retinopathy of Prematurity; Sildenafil Citrate; Sulfones; Vasodilator Agents

Topics: Humans; Hypertension, Pulmonary; Infant, Newborn; Infant, Premature; Male; Piperazines; Purines; Respiratory Distress Syndrome, Newborn; Retinopathy of Prematurity; Sildenafil Citrate; Sulfones; Vasodilator Agents