Retinopathy of prematurity
I. Describe the approach to establishing the diagnosis
A. Describe the etiology of this disease
1. Normal retinal vascular development begins during month 4 of gestation and ends by months 9-10
2. Normal development is altered by premature exposure to the extrauterine environment
B. Define the relevant aspects of epidemiology of the disease
1. Infants born weighing less than 1500 grams are at risk for serious visual sequelae
2. Risk of visual loss increases as gestational age and birth weight decrease
C. List the pertinent elements of the history
1. Birth weight
2. Gestational age at birth
3. Current and postconceptional age
4. Significant systemic illnesses
5. Selection of patients for screening – all premature infants with a birth weight less than 1500 grams, a gestational age less than 28 weeks, or with an unstable clinical course felt to be at high risk for retinopathy of prematurity (ROP) are examined
6. Timing of exams – infants are first examined at 4-6 weeks of age and then at least every 1-2 weeks thereafter, until vascularization proceeds to zone III or the risk of requiring treatment is passed (42-44 weeks postconception)
D. Describe pertinent clinical features
1. Zone – location of disease
a. Zone 1 = posterior pole; circle with radius twice the nerve-macula distance
b. Zone II= edge of zone I to a circle with radius equal to the distance from the optic nerve to the nasal ora serrata
c. Zone III = residual crescent anterior to zone II
2. Stage – severity of disease
a. Stage 1 = demarcation line (See Pediatrics Figure 37)
b. Stage 2 = ridge (See Pediatrics Figure 38)
c. Stage 3 = ridge with extraretinal fibrovascular proliferation
d. Stage 4 = subtotal retinal detachment
e. Stage 5 = total retinal detachment
3. Plus disease – marked vascular dilation and tortuosity of posterior pole vessels that meets or exceeds the amount seen in a standard photograph (See Pediatrics Figure 39) (See Pediatrics Figure 40)
4. Threshold disease – five contiguous or eight total clock hours of stage 3 in zone I or zone II with plus disease
5. Pre-threshold disease
a. Type I
i. Zone I, any stage with plus disease, or
ii. Zone I, stage 3 without plus disease, or
iii. Zone II, stage 2 or 3 with plus disease
b. Type II
i. Zone I, stage 1 or 2 without plus disease, or
ii. Zone II, stage 3 without plus disease
II. Define the risk factors
A. Low birth weight
B. Young gestational age at birth
C. Supplemental oxygen administration
D. Multiple birth
E. Birth outside a hospital with a neonatal intensive care unit
F. Caucasian race
G. Respiratory distress syndrome
H. Intraventricular hemorrhage
I. Sepsis
J. Poor weight gain
III. List the differential diagnosis
A. Early stages - Familial exudative vitreoretinopathy
B. Late stages – Other causes of leukocoria
1. Persistent fetal vasculature or persistent hyperplastic primary vitreous
2. Retinoblastoma
3. Norrie’s disease
4. Incontinentia pigmenti
5. Coats’ disease
6. Coloboma
7. Toxoplasmosis
IV. Describe patient management in terms of treatment and follow-up
A. Describe surgical therapy options
1. Cryotherapy
a. Cryotherapy for ROP Study – destruction of peripheral avascular retina significantly reduced risk of unfavorable visual outcome
b. Cryotherapy now used only if no or very poor view of retina
2. Laser photocoagulation
a. Early treatment for ROP Study –early treatment of high-risk pre-threshold ROP significantly reduced risk of unfavorable visual outcome
b. Performed within 48 hours of diagnosis of Type I ROP
c. Re-treatment sometimes necessary
3. Treatment options for retinal detachment
a. Observation only (some partial detachments)
b. Scleral buckle
c. Vitrectomy
V. List the complications of treatment, their prevention and management
A. Inadvertent laser burns
B. Intense postoperative inflammation – prevented by use of topical corticosteroids
C. Cataract
D. Glaucoma
E. Posterior synechiae – prevented by use of topical cycloplegic
F. Hyphema
G. Vitreous hemorrhage
H. Phthisis bulbi
VI. Describe disease-related complications
A. Retinal detachment – partial or total
B. Macular heterotopia (See Pediatrics Figure 41) (See Pediatrics Figure 42)
C. High myopia
D. Amblyopia
E. Strabismus
F. Anisometropia
G. Glaucoma
H. Phthisis bulbi
VII. Describe appropriate patient instructions
A. Introduction to basic concepts of ROP
B. Discussion of risks and benefits of laser treatment
C. Discussion of possibility of progression of disease despite treatment and need for re-treatment
D. Awareness of importance of timely and appropriate outpatient follow-up
Additional Resources
1. AAO, Basic and Clinical Science Course, Section 6: Pediatric Ophthalmology and Strabismus, 2004-2005.
2. AAO, Laser Photocoagulation of the Retina and Choroid, 1997, p.129-135.
3. AAO, Focal Points: Retinopathy of Prematurity, Module #11, 2001.
4. AAO, Focal Points: Pediatric Glaucoma, Module #5, 1997, p.5.
5. AAO, Focal Points: Current Management of Retinopathy of Prematurity, Module #3, 1993.
6. AAO, Focal Points: How to examine the eye of the Neonate, Module #1, 1989, p.4-5.
7. Fiedler AR. Preliminary results of treatment of eyes with high-risk prethreshold retinopathy of prematurity in the early treatment for retinopathy of prematurity randomized trial. Arch Ophthalmol. 2003;121:1769-71.
8. Hardy RJ, Palmer EA, Dobson V, et al. Risk analysis of prethreshold retinopathy of prematurity. Arch Ophthalmol. 2003;121:1697-701.
9. 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;121:1684-94.
10. Cole CH, Wright KW, Tarnow-Mordi W, et al. Resolving our uncertainty about oxygen therapy. Pediatrics. 2003;112:1415-9.
11. Lloyd J, Askie L, Smith J, et al. Supplemental oxygen for the treatment of prethreshold retinopathy of prematurity. Cochrane Database Syst Rev. 2003;(2):CD003482.
12. Reynolds JD, Dobson V, Quinn GE, et al. Evidence-based screening criteria for retinopathy of prematurity: natural history data from the CRYO-ROP and LIGHT-ROP studies. Arch Ophthalmol. 2002;120:1470-6.
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16. Tasman W. Ten-year follow-up from the CRYO-ROP study. Arch Ophthalmol. 2001;119:1200-1.
17. Cryotherapy for Retinopathy of Prematurity Cooperative Group. Contrast sensitivity at age 10 years in children who had threshold retinopathy of prematurity. Arch Ophthalmol. 2001;119:1129-33.
18. Cryotherapy for Retinopathy of Prematurity Cooperative Group. Multicenter Trial of Cryotherapy for Retinopathy of Prematurity: ophthalmological outcomes at 10 years. Arch Ophthalmol. 2001;119:1120-5.
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28. American Academy of Pediatrics. Section of Ophthalmology. Screening examination of premature infants for retinopathy of prematurity. Pediatrics 2001;108:809-11.
29. The STOP-ROP Multicenter Study Group. Supplemental Therapeutic Oxygen for Prethreshold Retinopathy of Prematurity (STOP-ROP), A Randomized, Controlled Trial. I: Primary Outcomes. Pediatrics 2000;105:295-310.
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31. Palmer EA, Flynn JT, Hardy RJ, et al. Incidence and early course of retinopathy of prematurity. Ophthalmology 1991;98:1628-40.
32. Schaffer DB, Palmer EA, Plotsky DF, et al. Prognostic factors in the natural course of retinopathy of prematurity. Ophthalmology 1993;100:230-7.
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35. Cryotherapy for Retinopathy of Prematurity Cooperative Group. Effect of Retinal Ablative Therapy for Threshold Retinopathy of Prematurity: Results of Goldmann Perimetry at the Age of 10 Years. Arch Ophthalmol 201;119:1120-5.
36. Hunter DG, Repka MX. Diode laser photocoagulation for threshold retinopathy of prematurity: a randomized study. Ophthalmology 1993;100:238-44.