A Paradigm Shift in the Prevention of Retinopathy of Prematurity

Raghuveer, Talkad S; Bloom, Barry T.

doi:10.1159/000322848

Cited by 43 publications

(48 citation statements)

References 187 publications

(94 reference statements)

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“…Our results in this animal model lend further support to previously reported post-administration feeding intolerance in clinical setting [10,13,14,15,16,20,21,22,23]. Findings from our study show that ophthalmic cyclopentolate administration produces detectable and measurable concentrations in serum samples from neonatal mice.…”

Section: Discussionsupporting

confidence: 91%

“…The exact mechanism of this effect is unknown, but may be due to intestinal relaxation and delayed gastric emptying secondary to the drug's anticholinergic activity. Cyclopentolate has also been associated with necrotizing enterocolitis, gastric dilation, paralytic ileus, and a decrease in gastric acid secretion [10,21,22,23]. Outside of their retinal disease, most pre-term infants are battling significant morbidity that would likely be worsened by decreased feeding and poor weight gain.…”

Section: Discussionmentioning

confidence: 99%

“…Multiple studies have found that mydriatic drops may cause systemic side effects in neonates, ranging from cardiovascular to enteric manifestations [11,12,13,14,15,16,17,18,19,20,21,22,23,24]. Those with lower body weights are especially prone to these sequelae [25], which may include flushing, tachycardia and increases in blood pressure, along with hallucinations, seizure activity, abdominal distension and feeding intolerance [11,12,13,14,15,16,17,18,19,20,21,22,23,24,26]. Because cyclopentolate readily crosses the blood-brain barrier, physostigmine remains the antidote of the choice [27].…”

Section: Introductionmentioning

confidence: 99%

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Systemic Effects of Ophthalmic Cyclopentolate on Body Weight in Neonatal Mice

et al. 2014

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Background: Cyclopentolate is standardly used in ophthalmologic examinations of neonates to facilitate screening for retinopathy of prematurity. Reports of systemic effects have raised concerns of an increased risk of feeding intolerance after the examinations. Objectives: The goal of this study was to evaluate systemic concentrations of cyclopentolate after ophthalmic administration, as well as assess changes in weight as an indirect measure of alteration in feeding. Methods: Neonatal mice were randomized into three groups to simulate a neonatal model for ophthalmic medication administration. The cyclopentolate group received a one-time administration of tetracaine, cyclopentolate, and phenylephrine ophthalmologic solutions in accordance with the protocol used at the children's hospital. The placebo group received the same ophthalmic drop administration, except for normal saline in place of cyclopentolate, and the control group received no ophthalmic drops and minimal handling. Daily weights and serum samples to measure systemic concentrations of cyclopentolate post-ophthalmic administration were assessed at baseline and for 7 days following drop administration. Results: Analysis of serum levels demonstrated detectability of systemic cyclopentolate after ophthalmic administration as early as 30 min (86 ng/ml), 1 h (60 ng/ml), and 24 h (6.2 ng/ml). There were also differences in weight gained on following ophthalmic administration observed between the cyclopentolate group and placebo group, with the cyclopentolate group weighing significantly less on days 3 and 7 (p = 0.02). Conclusions: Results indicate cyclopentolate is absorbed systemically and instillation of cyclopentolate decreases weight gain in neonatal mice compared to placebo. These preclinical findings provide rationale for further studies in neonatal patients.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Systemic Effects of Ophthalmic Cyclopentolate on Body Weight in Neonatal Mice

et al. 2014

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“…The WINROP (weight, insulin-like growth factor, neonatal ROP) algorithm is an online surveillance system based on weekly postnatal measurements of serum IGF-1 levels and body weight to evaluate the risk of developing sight-threating ROP [7,18]. Studies have validated this algorithm in Europe, South America, and the USA [7,11,15,19,20,21], but it has not yet been evaluated in a Chinese population.…”

Section: Introductionmentioning

confidence: 99%

The Use of the WINROP Screening Algorithm for the Prediction of Retinopathy of Prematurity in a Chinese Population

et al. 2013

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Background: Retinopathy of prematurity (ROP) is a gestational age (GA)-related illness that can lead to blindness in premature infants. Timely screening of premature infants could improve visual prognosis. Objective: To evaluate the WINROP algorithm as a method of predicting severe ROP in a Chinese population. Methods: 590 infants with a GA <32 weeks wereentered into an online surveillance system (www.winrop.com) that included ROP evaluations and weekly weight measurements from birth to a corrected GA of 40 weeks. If the rate of weight gain decreased to a certain degree, the algorithm signaled an alarm that the infant was at risk for developing sight-threatening ROP. Each infant was categorized as having no, mild, or severe ROP. Results: Among the 590 infants with a GA <32 weeks, an alarm was triggered in 85 infants (14.4%), 50 of which developed severe ROP and were identified in this alarm group. Twenty-seven infants triggered the alarm signal in the first week after birth and 7 infants triggered the alarm at birth. Seven of the infants developed proliferative ROP and the median GA at birth for these infants was 31 weeks. Conclusions: The WINROP system had a sensitivity of 87.5% in a Chinese population for the early identification of infants that developed severe ROP. Postnatal weight gain may help predict ROP in lower birth weight infants.

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“…The low concentrations of factors important for development that are normally provided in utero prevent the very immature retinas of extremely preterm infants from vascularising normally, which can precipitate the disease, [5][6][7][8][9][10][11] possibly with different effects during different developmental stages. Identification of postnatal factors that affect the risk for and the course of retinopathy of prematurity might allow neonatologists and ophthalmologists to attempt to prevent the disease and to limit comorbidities with which it shares modifiable risk factors.…”

Section: Introductionmentioning

confidence: 99%

Retinopathy of Prematurity

Stahl¹,

Hellström²,

Smith³

2016

Anti-Angiogenic Therapy in Ophthalmology

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The immature retinas of preterm newborns are susceptible to insults that disrupt neurovascular growth, which leads to retinopathy of prematurity. Suppression of growth factors due to hyperoxia and loss of the maternal-fetal interaction result in an arrest of retinal vascularisation (phase 1). Subsequently, the increasingly metabolically active, yet poorly vascularised, retina becomes hypoxic, stimulating growth factor-induced vasoproliferation (phase 2), which can cause retinal detachment. In very premature infants, controlled oxygen administration reduces but does not eliminate retinopathy of prematurity. Identification and control of factors that contribute to development of retinopathy of prematurity is essential to prevent progression to severe sightthreatening disease and to limit comorbidities with which the disease shares modifiable risk factors. Strategies to prevent retinopathy of prematurity will depend on optimisation of oxygen saturation, nutrition, and normalisation of concentrations of essential factors such as insulin-like growth factor 1 and ω-3 polyunsaturated fatty acids, as well as curbing of the effects of infection and inflammation to promote normal growth and limit suppression of neurovascular development.

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A Paradigm Shift in the Prevention of Retinopathy of Prematurity

Cited by 43 publications

References 187 publications

Systemic Effects of Ophthalmic Cyclopentolate on Body Weight in Neonatal Mice

Systemic Effects of Ophthalmic Cyclopentolate on Body Weight in Neonatal Mice

The Use of the WINROP Screening Algorithm for the Prediction of Retinopathy of Prematurity in a Chinese Population

Retinopathy of Prematurity

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