eMedicine Specialties > Pediatrics: Cardiac Disease and Critical Care Medicine > Neonatology

Retinopathy of Prematurity: Treatment & Medication

Author: KN Siva Subramanian, MD, Professor of Pediatrics and Obstetrics/Gynecology, Chief of Neonatal Perinatal Medicine, Director of Nurseries, Georgetown University Hospital
Coauthor(s): Monisha Bahri, MBBS, MD, Fellow in Neonatal/Perinatal Medicine, Department of Neonatology, Georgetown University Hospital; Gonzalo (Vike) Vicente, MD, FAAP, Consulting Ophthalmologist, Eye Doctors of Washington
Contributor Information and Disclosures

Updated: Jun 29, 2009

Treatment

Medical Care

  • Medical care of retinopathy of prematurity (ROP) consists of ophthalmologic screening of appropriate infants. No standard medical therapies are available at this time.
  • Ongoing research is examining the potential use of intravitreally injected antineovascularization drugs, such as bevacizumab (Avastin).15  These drugs have been successfully used in patients with other forms of neovascularization, such as diabetic retinopathy. Other treatments may involve restoring normal levels of insulinlike growth factor (IGF)-1 and omega-3-polyunsaturated fatty acids (PUFAs) in the developing retina, as proposed by Chen and Smith.16,17,18
  • The Supplemental Therapeutic Oxygen for Prethreshold Retinopathy of Prematurity (STOP-ROP) Trial assessed the effect of supplemental oxygen in reducing the probability of progression to threshold retinopathy of prematurity and the need for peripheral retinal ablation in infants with prethreshold retinopathy of prematurity.3 The results of the trial showed no reduction in the infants who required ablative surgery. A post hoc subgroup analysis showed that infants without plus disease may be more responsive to supplemental oxygen therapy (46% progression in the conventional arm vs 32% progression in the supplemental arm) than infants with plus disease (52% progression in the conventional arm vs 57% in the supplemental arm). Supplemental oxygen increased the risk of adverse pulmonary events (8.5% conventional arm vs 13.2% in the supplemental arm).

Surgical Care

  • Ablative surgery
    • If threshold disease is present, perform ablative surgery.
    • Ablative therapy currently consists of cryotherapy or laser surgery to destroy the avascular areas of the retina.
    • The average gestational age (GA) at which surgery is necessary is usually 37-40 weeks.
    • If the retinopathy of prematurity continues to progress, more than one treatment may be required.
  • Cryotherapy
    • A randomized prospective trial of cryotherapy showed a 50% reduction in retinal detachment in treated eyes versus nontreated eyes.
    • Beneficial effects were observed in infants with threshold disease, defined as 5 contiguous clock hours of stage III disease with plus disease or 8 noncontiguous clock hours of stage III disease with plus disease.
  • Laser surgery
    • Currently, laser surgery is preferred to cryotherapy because it may be more effective in treating zone I disease and causes less inflammation. Laser photocoagulation appears to be associated with outcomes in structure and function that are at least as good as those of cryotherapy 7 years after therapy.19 In addition, visual acuity and refractive error data suggest that laser surgery may have an advantage over cryotherapy, and evidence suggests that laser surgery is easier to perform and better tolerated by the infants. Cryotherapy is still the preferred treatment option when the view of the retina is limited by media opacities.
    • Laser surgery has been used more recently than cryotherapy, and whether the slightly improved outcomes with laser surgery are attributable to changes in the care of high-risk neonates (eg, antenatal glucocorticoid therapy, surfactant use) is unclear. However, cryotherapy has been rigorously evaluated in a multicenter prospective randomized fashion, and the 10-year follow-up data show long-term value in preserving visual acuity in eyes with threshold retinopathy of prematurity.8
  • Early treatment
    • The Early Treatment for Retinopathy of Prematurity (ET-ROP) Trial showed that early treatment of high-risk prethreshold retinopathy of prematurity significantly reduced unfavorable retinopathy of prematurity outcomes at age 9 months and at age 2 years.20,21  Patients in this study had one eye randomized to "early" retinal ablative therapy. Eyes treated had type 1 retinopathy of prematurity, defined as zone I with plus disease and any stage retinopathy of prematurity; zone I with stage III and no plus disease; or zone II, stage II or III, and plus disease.
    • The investigators subsequently compared their results from this ET-ROP study with those of the Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) study, with respect to incidence and early course of retinopathy of prematurity. The incidence, time of onset of any disease and prethreshold disease, and rate of progression have changed little since the mid 1980s. The ET-ROP had more cases of prethreshold disease (36.9% in ET-ROP and 27.1% in CRYO-ROP) and more zone I retinopathy of prematurity.

Medication

  • If a patient has prethreshold retinopathy of prematurity (ROP), some centers try to maintain normal serum levels of vitamin E.
  • Vitamin E use was evaluated in a meta-analysis, and levels should be maintained within the reference range in patients at high risk for severe retinopathy of prematurity.

More on Retinopathy of Prematurity

Overview: Retinopathy of Prematurity
Differential Diagnoses & Workup: Retinopathy of Prematurity
Treatment & Medication: Retinopathy of Prematurity
Follow-up: Retinopathy of Prematurity
Multimedia: Retinopathy of Prematurity
References
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References

  1. [Best Evidence] Dhaliwal CA, Fleck BW, Wright E, Graham C, McIntosh N. Retinopathy of prematurity in small-for-gestational age infants compared with those of appropriate size for gestational age. Arch Dis Child Fetal Neonatal Ed. May 2009;94(3):F193-5. [Medline].

  2. Hussain N, Clive J, Bhandari V. Current incidence of retinopathy of prematurity, 1989-1997. Pediatrics. Sep 1999;104(3):e26. [Medline]. [Full Text].

  3. STOP-ROP. Supplemental Therapeutic Oxygen for Prethreshold Retinopathy Of Prematurity, a randomized, controlled trial. I: primary outcomes. Pediatrics. Feb 2000;105(2):295-310. [Medline].

  4. Kim TI, Sohn J, Pi SY, Yoon YH. Postnatal risk factors of retinopathy of prematurity. Paediatr Perinat Epidemiol. Mar 2004;18(2):130-4. [Medline].

  5. Shah VA, Yeo CL, Ling YL, Ho LY. Incidence, risk factors of retinopathy of prematurity among very low birth weight infants in Singapore. Ann Acad Med Singapore. Mar 2005;34(2):169-78. [Medline].

  6. Gilbert C, Fielder A, Gordillo L, et al. Characteristics of infants with severe retinopathy of prematurity in countries with low, moderate, and high levels of development: implications for screening programs. Pediatrics. May 2005;115(5):e518-25. [Medline].

  7. Repka MX, Summers CG, Palmer EA, et al. The incidence of ophthalmologic interventions in children with birth weights less than 1251 grams. Results through 5 1/2 years. Cryotherapy for Retinopathy of Prematurity Cooperative Group. Ophthalmology. Sep 1998;105(9):1621-7. [Medline].

  8. Cryotherapy for Retinopathy of Prematurity Cooperative Group. Multicenter Trial of Cryotherapy for Retinopathy of Prematurity: ophthalmological outcomes at 10 years. Arch Ophthalmol. Aug 2001;119(8):1110-8. [Medline].

  9. Tadesse M, Dhanireddy R, Mittal M, Higgins RD. Race, Candida sepsis, and retinopathy of prematurity. Biol Neonate. 2002;81(2):86-90. [Medline].

  10. Bizzarro MJ, Hussain N, Jonsson B, et al. Genetic susceptibility to retinopathy of prematurity. Pediatrics. Nov 2006;118(5):1858-63. [Medline].

  11. Hellstrom A, Hard AL, Engstrom E, et al. Early weight gain predicts retinopathy in preterm infants: new, simple, efficient approach to screening. Pediatrics. Apr 2009;123(4):e638-45. [Medline].

  12. International Committee for the Classification of Retinopathy of Prematurity. The International Classification of Retinopathy of Prematurity revisited. Arch Ophthalmol. Jul 2005;123(7):991-9. [Medline].

  13. [Guideline] AAP, AAO, and AAPOS. Screening examination of premature infants for retinopathy of prematurity. Pediatrics. Feb 2006;117(2):572-6. [Medline].

  14. Subhani M, Combs A, Weber P, et al. Screening guidelines for retinopathy of prematurity: the need for revision in extremely low birth weight infants. Pediatrics. Apr 2001;107(4):656-9. [Medline].

  15. Mintz-Hittner HA, Kuffel RR Jr. Intravitreal injection of bevacizumab (avastin) for treatment of stage 3 retinopathy of prematurity in zone I or posterior zone II. Retina. Jun 2008;28(6):831-8. [Medline].

  16. Chen J, Smith LE. Retinopathy of prematurity. Angiogenesis. 2007;10(2):133-40. [Medline].

  17. Connor KM, SanGiovanni JP, Lofqvist C, Aderman CM, Chen J, Higuchi A, et al. Increased dietary intake of omega-3-polyunsaturated fatty acids reduces pathological retinal angiogenesis. Nat Med. Jul 2007;13(7):868-73. [Medline].

  18. Mantagos IS, Vanderveen DK, Smith LE. Emerging treatments for retinopathy of prematurity. Semin Ophthalmol. Mar-Apr 2009;24(2):82-6. [Medline].

  19. Shalev B, Farr AK, Repka MX. Randomized comparison of diode laser photocoagulation versus cryotherapy for threshold retinopathy of prematurity: seven-year outcome. Am J Ophthalmol. Jul 2001;132(1):76-80. [Medline].

  20. VanderVeen DK, Coats DK, Dobson V, et al. Prevalence and course of strabismus in the first year of life for infants with prethreshold retinopathy of prematurity: findings from the Early Treatment for Retinopathy of Prematurity study. Arch Ophthalmol. Jun 2006;124(6):766-73. [Medline].

  21. Good WV, Hardy RJ, Dobson V, et al. The incidence and course of retinopathy of prematurity: findings from the earlytreatment for retinopathy of prematurity study. Pediatrics. Jul 2005;116(1):15-23. [Medline].

  22. Console V, Gagliardi L, De Giorgi A, De Ponti E. Retinopathy of prematurity and antenatal corticosteroids. The Italian ROP Study Group. Acta Biomed Ateneo Parmense. 1997;68 Suppl 1:75-9. [Medline].

  23. Wright KW, Sami D, Thompson L, Ramanathan R, Joseph R, Farzavandi S. A physiologic reduced oxygen protocol decreases the incidence of threshold retinopathy of prematurity. Trans Am Ophthalmol Soc. 2006;104:78-84. [Medline].

  24. Wallace DK. Oxygen saturation levels and retinopathy of prematurity--are we on target?. J AAPOS. Oct 2006;10(5):382-3. [Medline].

  25. [Guideline] AAP, AAPOS, AAO. Screening examination of premature infants for retinopathy of prematurity. A joint statement of the American Academy of Pediatrics, the American Association for Pediatric Ophthalmology and Strabismus, and the American Academy of Ophthalmology. Pediatrics. Aug 1997;100(2 Pt 1):273. [Medline]. [Full Text].

  26. Bremer DL, Palmer EA, Fellows RR, et al. Strabismus in premature infants in the first year of life. Cryotherapy for Retinopathy of Prematurity Cooperative Group. Arch Ophthalmol. Mar 1998;116(3):329-33. [Medline].

  27. Brooks SE, Marcus DM, Gillis D, et al. The effect of blood transfusion protocol on retinopathy of prematurity: A prospective, randomized study. Pediatrics. Sep 1999;104(3 Pt 1):514-8. [Medline].

  28. Committee for the Classification of Retinopathy of Prematurity. An international classification of retinopathy of prematurity. Arch Ophthalmol. Aug 1984;102(8):1130-4. [Medline].

  29. Connolly BP, McNamara JA, Sharma S, et al. A comparison of laser photocoagulation with trans-scleral cryotherapy in the treatment of threshold retinopathy of prematurity. Ophthalmology. Sep 1998;105(9):1628-31. [Medline].

  30. Cryotherapy for Retinopathy of Prematurity Cooperative Group. Multicenter trial of cryotherapy for retinopathy of prematurity: preliminary results. Pediatrics. May 1988;81(5):697-706. [Medline].

  31. Dani C, Reali MF, Bertini G, et al. The role of blood transfusions and iron intake on retinopathy of prematurity. Early Hum Dev. Apr 2001;62(1):57-63. [Medline].

  32. 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. Dec 2003;121(12):1684-94. [Medline].

  33. Gelman R, Martinez-Perez ME, Vanderveen DK, Moskowitz A, Fulton AB. Diagnosis of plus disease in retinopathy of prematurity using Retinal Image multiScale Analysis. Invest Ophthalmol Vis Sci. Dec 2005;46(12):4734-8. [Medline].

  34. Good WV. The Early Treatment for Retinopathy Of Prematurity Study: structural findings at age 2 years. Br J Ophthalmol. Nov 2006;90(11):1378-82. [Medline].

  35. Higgins RD, Mendelsohn AL, DeFeo MJ, et al. Antenatal dexamethasone and decreased severity of retinopathy of prematurity. Arch Ophthalmol. May 1998;116(5):601-5. [Medline].

  36. Hunter DG, Repka MX. Diode laser photocoagulation for threshold retinopathy of prematurity. A randomized study. Ophthalmology. Feb 1993;100(2):238-44. [Medline].

  37. Johnson L, Quinn GE, Abbasi S, et al. Severe retinopathy of prematurity in infants with birth weights less than 1250 grams: incidence and outcome of treatment with pharmacologic serum levels of vitamin E in addition to cryotherapy from 1985 to 1991. J Pediatr. Oct 1995;127(4):632-9. [Medline].

  38. Kennedy JE, Todd DA, John E. Progress in Retinopathy of Prematurity. In: Premature Birth and Retinopathy of Prematurity. 1997:73-5.

  39. Lee SK, Normand C, McMillan D, et al. Evidence for changing guidelines for routine screening for retinopathy of prematurity. Arch Pediatr Adolesc Med. Mar 2001;155(3):387-95. [Medline].

  40. McNamara JA, Tasman W, Brown GC, Federman JL. Laser photocoagulation for stage 3+ retinopathy of prematurity. Ophthalmology. May 1991;98(5):576-80. [Medline].

  41. O'Keefe M, O'Reilly J, Lanigan B. Longer-term visual outcome of eyes with retinopathy of prematurity treated with cryotherapy or diode laser. Br J Ophthalmol. Nov 1998;82(11):1246-8. [Medline]. [Full Text].

  42. Palmer EA, Hardy RJ, Dobson V, et al. 15-year outcomes following threshold retinopathy of prematurity: final resultsfrom the multicenter trial of cryotherapy for retinopathy of prematurity. Arch Ophthalmol. Mar 2005;123(3):311-8. [Medline].

  43. Pearce IA, Pennie FC, Gannon LM, et al. Three year visual outcome for treated stage 3 retinopathy of prematurity: cryotherapy versus laser. Br J Ophthalmol. Nov 1998;82(11):1254-9. [Medline].

  44. Phelps DL. Retinopathy of prematurity. Pediatr Rev. Feb 1995;16(2):50-6. [Medline].

  45. Quinn GE, Dobson V, Kivlin J, et al. Prevalence of myopia between 3 months and 5 1/2 years in preterm infants with and without retinopathy of prematurity. Cryotherapy for Retinopathy of Prematurity Cooperative Group. Ophthalmology. Jul 1998;105(7):1292-300. [Medline].

  46. Raju TN, Langenberg P, Bhutani V, Quinn GE. Vitamin E prophylaxis to reduce retinopathy of prematurity: a reappraisal of published trials. J Pediatr. Dec 1997;131(6):844-50. [Medline].

  47. 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 [see comments]. N Engl J Med. May 28 1998;338(22):1572-6. [Medline].

  48. Saunders RA, Donahue ML, Christmann LM, et al. Racial variation in retinopathy of prematurity. The Cryotherapy for Retinopathy of Prematurity Cooperative Group. Arch Ophthalmol. May 1997;115(5):604-8. [Medline].

  49. Travassos A, Teixeira S, Ferreira P, et al. Intravitreal bevacizumab in aggressive posterior retinopathy of prematurity. Ophthalmic Surg Lasers Imaging. May-Jun 2007;38(3):233-7. [Medline].

  50. Vanderveen DK, Mansfield TA, Eichenwald EC. Lower oxygen saturation alarm limits decrease the severity of retinopathy of prematurity. J AAPOS. Oct 2006;10(5):445-8. [Medline].

  51. Wallace DK. Oxygen saturation levels and retinopathy of prematurity--are we on target?. J AAPOS. Oct 2006;10(5):382-3. [Medline].

  52. Young TL, Anthony DC, Pierce E, et al. Histopathology and vascular endothelial growth factor in untreated and diode laser-treated retinopathy of prematurity. J AAPOS. Jun 1997;1(2):105-10. [Medline].

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Further Reading

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Keywords

retinopathy of prematurity, ROP, retrolental fibroplasia, retinal neovascularization, extremely low birth weight infants, ELBW, respiratory distress syndrome, RSD, bronchopulmonary dysplasia, BPD, sepsis, retinal hypoxia, tortuosity of vessels, maternal preeclampsia, pulmonary hemorrhage, visual impairment, blindness, myopia, amblyopia, strabismus, patent ductus arteriosus, intraventricular hemorrhage, visual impairment, blindness, supplemental oxygen, treatment, diagnosis

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Contributor Information and Disclosures

Author

KN Siva Subramanian, MD, Professor of Pediatrics and Obstetrics/Gynecology, Chief of Neonatal Perinatal Medicine, Director of Nurseries, Georgetown University Hospital
KN Siva Subramanian, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for the Advancement of Science, American College of Nutrition, American Society for Parenteral and Enteral Nutrition, American Society of Law Medicine and Ethics, New York Academy of Sciences, and Southern Society for Pediatric Research
Disclosure: Nothing to disclose.

Coauthor(s)

Monisha Bahri, MBBS, MD, Fellow in Neonatal/Perinatal Medicine, Department of Neonatology, Georgetown University Hospital
Monisha Bahri, MBBS, MD is a member of the following medical societies: American Academy of Pediatrics, Indian Academy of Pediatrics, and Medical Council of India
Disclosure: Nothing to disclose.

Gonzalo (Vike) Vicente, MD, FAAP, Consulting Ophthalmologist, Eye Doctors of Washington
Gonzalo (Vike) Vicente, MD, FAAP is a member of the following medical societies: American Academy of Ophthalmology, American Academy of Pediatrics, American Association for Pediatric Ophthalmology and Strabismus, and American Medical Association
Disclosure: Nothing to disclose.

Medical Editor

Oussama Itani, MD, FAAP, FACN, Clinical Associate Professor of Pediatrics and Human Development, Michigan State University; Medical Director, Department of Neonatology, Borgess Medical Center
Oussama Itani, MD, FAAP, FACN is a member of the following medical societies: American Academy of Pediatrics, American College of Nutrition, American College of Physician Executives, and American Heart Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Arun K Pramanik, MD, MBBS, Professor of Pediatrics, Director of Neonatal Fellowship, Louisiana State University Health Sciences Center
Arun K Pramanik, MD, MBBS is a member of the following medical societies: American Academy of Pediatrics, American Thoracic Society, National Perinatal Association, and Southern Society for Pediatric Research
Disclosure: Nothing to disclose.

CME Editor

Carol L Wagner, MD, Professor of Pediatrics, Medical University of South Carolina
Carol L Wagner, MD is a member of the following medical societies: American Academy of Pediatrics, American Chemical Society, American Medical Women's Association, American Public Health Association, American Society for Bone and Mineral Research, American Society for Clinical Nutrition, Massachusetts Medical Society, National Perinatal Association, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Chief Editor

Ted Rosenkrantz, MD, Professor, Departments of Pediatrics and Obstetrics/Gynecology, Division of Neonatal-Perinatal Medicine, University of Connecticut School of Medicine
Ted Rosenkrantz, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Pediatric Society, Connecticut State Medical Society, Eastern Society for Pediatric Research, and Society for Pediatric Research
Disclosure: Nothing to disclose.

 
 
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