Retinopathy of Prematurity Ophthalmologic Approach Treatment & Management
- Author: Mounir Bashour, MD, PhD, CM, FRCSC, FACS; Chief Editor: Hampton Roy, Sr, MD more...
Although oxygen therapy has been blamed for ROP progression in the past, many physicians believe that maximizing the oxygen saturation in these critical babies will induce regression in prethreshold disease. STOP-ROP (Supplemental Therapeutic Oxygen for Prethreshold Retinopathy Of Prematurity), a multicentered national study, found that no benefit was achieved by keeping the oxygen saturation above 95%. However, higher oxygen saturation levels were not found to worsen the disease in prethreshold babies.
Because ROP progresses sequentially and timely treatment can reduce the risk of visual loss, at-risk preterm infants must be examined at proper times and intervals. A January 2013 policy statement from the American Academy of Pediatrics on screening for ROP provides screening recommendations, including descriptions of the following :
Criteria for screening
Equipment and methods for retinal examinations for ROP
Examiner qualifications and reporting criteria
Timing of the first retinal examination, based on the infant’s postmenstrual age (gestational age at birth plus chronologic age)
There appears to be a lower incidence of very high myopia (≥8.00 diopters) when ROP is treated with intravitreal bevacizumab compared with conventional lasers,[15, 16] on the basis of results from the Bevacizumab Eliminates the Angiogenic Threat for ROP (BEAT-ROP) Cooperative Group study, which randomized 109 children (211 eyes) as infants to intravitreal bevacizumab or conventional laser treatment and then compared refractive outcomes at age 2.5 years. Moreover, myopia in the laser group was linked to greater numbers of laser applications, with an increase of -0.14 D for every 100 laser applications.
Among infants with zone I ROP, very high myopia developed in 2 of 52 eyes (3.8%) in the bevacizumab group and 18 of 35 eyes (51.4%) in the laser group (P < .001); among those with zone II posterior ROP, very high myopia developed in 1 of 58 eyes (1.7%) in the bevacizumab group and in 24 of 66 eyes (36.4%) in the laser group (P < .001).[15, 16]
Cryotherapy was the original mode of treatment (since the 1970s). The procedure may be completed with general or topical anesthesia. It involves approximately 50 applications of a freezing probe under direct visualization with cryo applications to the avascular retina anterior to the fibrovascular ridge. The stress of the procedure may require assisted ventilation after the procedure. The most common complications include intraocular hemorrhage, conjunctival hematoma, conjunctival laceration, and bradycardia.
Laser surgery (eg, xenon, argon, diode) has been shown to be as effective as cryotherapy for ROP. The systemic adverse effects are significantly less, the ocular tissues are less traumatized, posterior zone 1 disease is treated easily, general anesthesia is not necessary, and, as many studies show, there is less incidence of late complications. Complications include corneal haze, burns of the iris, cataracts, and intraocular hemorrhages.
The use of diode laser therapy in extremely preterm infants with ROP appears not only to halt disease progression but also leads to good visual outcomes for most of these infants, thereby apparently offering similar structural and visual outcomes to those of low and very low birth weight infants with this condition.[17, 18]
Scleral buckling surgery and/or vitrectomy is usually performed for stages 4 and 5. Some surgeons recommend surgery for stage 4A, while others do not think surgery should be performed because of the risks and unproven benefit. Although some surgeons advocate surgery for stage 5, the surgeon with the most experience (S.T. Charles, MD, personal communication) no longer recommends surgery because of the poor anatomical and visual prognosis.
According to the largest reported case series in the world, lens-sparing vitrectomy to correct early degrees of retinal detachment results in excellent lens clarity and vision in the majority of infants with retinopathy of prematurity. Success rates for retinal reattachment with a single surgery were approximately 89% for infants with stage 4A retinopathy. Success rates for stage 4B retinopathy were 60%. The procedure was less successful in infants with stage 5 retinopathy, with an 18% success rate.
An ophthalmology consultation is essential in a premature infant born weighing less than 1500 g and/or younger than 32 weeks' gestation (as defined by the attending neonatologist). Also, selected infants with a birth weight of 1500-2000 g or a gestational age of more than 32 weeks with an unstable clinical course, including those requiring cardiorespiratory support and who are believed by their attending pediatrician or neonatologist to be at high risk, should have retinal screening examinations performed after pupillary dilation using binocular indirect ophthalmoscopy to detect ROP. One examination is sufficient only if it unequivocally shows the retina to be fully vascularized in each eye. The ophthalmologist chosen should be one with the most experience in screening or treating this disease. A review of two randomized crossover trials performed in single centers found that the application of topical proparacaine 30 seconds before the evaluation brings about a reduction in pain scores, particularly atthemoment of speculum insertion.
An ophthalmologist experienced in this modality should perform laser or cryotherapy surgery.
Scleral buckle surgery and vitrectomy techniques in these small eyes should be left in the hands of experienced surgeons.
Practitioners involved in the ophthalmologic care of premature infants should be aware that the retinal findings that require strong consideration of ablative treatment were revised according to the Early Treatment for Retinopathy of Prematurity Randomized Trial study. The finding of threshold ROP, as defined in the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity, may no longer be the preferred time of intervention.
Treatment may also be initiated for the following retinal findings:
Zone 1 ROP - Any stage, with plus disease
Zone 1 ROP - Stage 3, with no plus disease
Zone 2 ROP - Stage 2 or 3, with plus disease
The number of clock hours of disease may no longer be the determining factor in recommending ablative treatment. Treatment should generally be accomplished, when possible, within 72 hours of determination of treatable disease to minimize the risk of retinal detachment.
Vitamin E is not recommended in infants who weigh less than 1500 g.
American Academy of Pediatrics Section on Ophthalmology; American Academy of Ophthalmology; American Association for Pediatric Ophthalmology and Strabismus; American Association of Certified Orthoptists. Screening examination of premature infants for retinopathy of prematurity. Pediatrics. 2013 Jan. 131(1):189-95. [Medline]. [Full Text].
Terry TL. Extreme prematurity and fibroplastic overgrowth of persistent vascular sheath behind each crystalline lens I. Preliminary report. Am J Ophthalmol. 1942. 25:203-4.
Campbell K. Intensive oxygen therapy as a possible cause for retrolental fibroplasia. A clinical approach. Med J Austr. 1951. 2:48-50.
Kretzer FL, Hittner HM. Retinopathy of prematurity: clinical implications of retinal development. Arch Dis Child. 1988 Oct. 63(10 Spec No):1151-67. [Medline].
Ashton N. Oxygen and the retinal blood vessels. Trans Ophthalmol Soc U K. 1980 Sep. 100(3):359-62. [Medline].
Csak K, Szabo V, Szabo A, et al. Pathogenesis and genetic basis for retinopathy of prematurity. Front Biosci. 2006 Jan 1. 11:908-20. [Medline].
Fielder AR, Shaw DE, Robinson J, et al. Natural history of retinopathy of prematurity: a prospective study. Eye. 1992. 6 (Pt 3):233-42. [Medline].
Varughese S, Gilbert C, Pieper C, et al. Retinopathy of prematurity in South Africa: an assessment of needs, resources and requirements for screening programmes. Br J Ophthalmol. 2008 Jul. 92(7):879-82. [Medline].
Palmer EA, Flynn JT, Hardy RJ, et al. Incidence and early course of retinopathy of prematurity. The Cryotherapy for Retinopathy of Prematurity Cooperative Group. Ophthalmology. 1991 Nov. 98(11):1628-40. [Medline].
Wallace DK, Freedman SF, Hartnett ME, Quinn GE. Predictive Value of Pre-plus Disease in Retinopathy of Prematurity. Arch Ophthalmol. 2011 May. 129(5):591-6. [Medline].
Tolsma KW, Allred EN, Chen ML, et al. Neonatal bacteremia and retinopathy of prematurity: the ELGAN study. Arch Ophthalmol. 2011 Dec. 129(12):1555-63. [Medline].
Melville N. Fluorescein Angiography Details Vasculature in ROP. Medscape Medical News. Available at http://www.medscape.com/viewarticle/823289. Accessed: April 14, 2014.
American Association for Pediatric Ophthalmology and Strabismus (AAPOS) 2014: Abstract 10. Presented April 3, 2014.
Lajoie A, Koreen S, Wang L, et al. Retinopathy of prematurity management using single-image vs multiple-image telemedicine examinations. Am J Ophthalmol. 2008 Aug. 146(2):298-309. [Medline].
Geloneck MM, Chuang AZ, Clark WL, et al, for the BEAT-ROP Cooperative Group. Refractive outcomes following bevacizumab monotherapy compared with conventional laser treatment: a randomized clinical trial. JAMA Ophthalmol. 2014 Aug 7. [Medline].
Boggs W. Lower risk of very high myopia with vevacizumab for retinopathy of prematurity. Reuters Health Information. August 14, 2014. [Full Text].
Roach L. Laser treatment halts retinopathy in extreme prematurity. Medscape Medical News. April 4, 2013. [Full Text].
Gunn DJ, Cartwright DW, Yuen SA, Gole GA. Treatment of retinopathy of prematurity in extremely premature infants over an 18-year period. Clin Experiment Ophthalmol. 2013 Mar. 41(2):159-66. [Medline].
Harrison P. Lens Clarity Excellent With Vitrectomy in Early Retinopathy. Medscape Medical News. Available at http://www.medscape.com/viewarticle/810151. Accessed: September 11, 2013.
Dempsey E, McCreery K. Local anaesthetic eye drops for prevention of pain in preterm infants undergoing screening for retinopathy of prematurity. Cochrane Database Syst Rev. 2011 Sep 7. 9:CD007645. [Medline].
Repka MX, Hardy RJ, Phelps DL, et al. Surfactant prophylaxis and retinopathy of prematurity. Arch Ophthalmol. 1993 May. 111(5):618-20. [Medline].
Wu WC, Yeh PT, Chen SN, Yang CM, Lai CC, Kuo HK. Effects and complications of bevacizumab use in patients with retinopathy of prematurity: a multicenter study in taiwan. Ophthalmology. 2011 Jan. 118(1):176-83. [Medline].
Mintz-Hittner HA, Kennedy KA, Chuang AZ. Efficacy of intravitreal bevacizumab for stage 3+ retinopathy of prematurity. N Engl J Med. 2011 Feb 17. 364(7):603-15. [Medline].
Cryotherapy for Retinopathy of Prematurity Cooperative Group. Multicenter trial of cryotherapy for retinopathy of prematurity. One-year outcome--structure and function. Arch Ophthalmol. 1990 Oct. 108(10):1408-16. [Medline].
Early Treatment For Retinopathy Of Prematurity Cooperative Group. Revised indications for the treatment of retinopathy of prematurity: results of the early treatment for retinopathy of prematurity randomized trial. Arch Ophthalmol. 2003 Dec. 121(12):1684-94. [Medline].
Laser ROP Study Group. Laser therapy for retinopathy of prematurity. Arch Ophthalmol. 1994 Feb. 112(2):154-6. [Medline].
Phelps DL. Retinopathy of prematurity: an estimate of vision loss in the United States--1979. Pediatrics. 1981 Jun. 67(6):924-5. [Medline].
Repka MX, Tung B, Good WV, et al. Outcome of eyes developing retinal detachment during the Early Treatment for Retinopathy of Prematurity Study (ETROP). Arch Ophthalmol. 2006 Jan. 124(1):24-30. [Medline].
Reynolds JD, Hardy RJ, Kennedy KA, et al. Lack of efficacy of light reduction in preventing retinopathy of prematurity. Light Reduction in Retinopathy of Prematurity (LIGHT-ROP) Cooperative Group. N Engl J Med. 1998 May 28. 338(22):1572-6. [Medline].
Schaffer DB, Palmer EA, Plotsky DF, et al. Prognostic factors in the natural course of retinopathy of prematurity. The Cryotherapy for Retinopathy of Prematurity Cooperative Group. Ophthalmology. 1993 Feb. 100(2):230-7. [Medline].
Section on Ophthalmology American Academy of Pediatrics, American Academy of Ophthalmology, American Association for Pediatric Ophthalmology and Strabismus. Screening examination of premature infants for retinopathy of prematurity. Pediatrics. 2006 Feb. 117(2):572-6. [Medline].
Supplemental Therapeutic Oxygen for Prethreshold Retinopathy Of Prematurity (STOP-ROP), a randomized, controlled trial. I: primary outcomes. Pediatrics. 2000 Feb. 105(2):295-310. [Medline].
The Committee for the Classification of Retinopathy of Prematurity. An international classification of retinopathy of prematurity. Arch Ophthalmol. 1984 Aug. 102(8):1130-4. [Medline].
Fang JL, Sorita A, Carey WA, Colby CE, Murad MH, Alahdab F. Interventions To Prevent Retinopathy of Prematurity: A Meta-analysis. Pediatrics. 2016 Mar 9. [Medline].
Eldweik L, Mantagos IS. Role of VEGF Inhibition in the Treatment of Retinopathy of Prematurity. Semin Ophthalmol. 2016. 31 (1-2):163-8. [Medline].
Cao JH, Wagner BD, McCourt EA, Cerda A, Sillau S, Palestine A, et al. The Colorado-retinopathy of prematurity model (CO-ROP): postnatal weight gain screening algorithm. J AAPOS. 2016 Feb. 20 (1):19-24. [Medline].