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PEDIATRICS Vol. 111 No. 4 April 2003, pp. 885-886


COMMENTARY

Implications of the Natural Course of Retinopathy of Prematurity

Abbreviations: ROP, retinopathy of prematurity • CRYO-ROP, Outcome Study of Cryotherapy and Retinopathy of Prematurity • stage 3+, stage 3 ROP with plus disease

Retinopathy of prematurity (ROP) is a derangement of vascular development in the premature infant retina. A tangled network of neovascular channels supplants the orderly arborization that would otherwise continue until the entire retina was supplied with a normal vascular tree. Unchecked neovascularization can lead to local scarring, contracture, and detachment of the retina, with or without intraocular hemorrhage. Extensive retinal detachment in premature infants typically causes severe visual impairment, even with successful surgical reattachment of the retina.

Surgical intervention (typically at ~32–42 postmenstrual weeks) by ablation of the more peripheral unvascularized part of the retina with laser therapy has become the preferred treatment modality in the United States and many other countries. Because this is effective in improving vision outcomes of severely affected cases, there is a natural eagerness to treat threatening ROP earlier than was done in the Multicenter Trial of Cryotherapy and Outcome Study of Retinopathy of Prematurity (CRYO-ROP). Thus, numerous formerly debatable cases now tend to go to treatment. The optimal indications for this treatment are undergoing professional discussion and formal study.

Although two thirds of infants who are born weighing 1250 g or less develop ROP, only ~6% require treatment.1 A recent report on the extended natural course of ROP (without ablative retinal therapy) at age 6 in >1000 children enrolled at a subgroup of CRYO-ROP centers not only confirms that most cases of ROP spontaneously go on to develop good vision, but also highlights how severe the ROP can become and still undergo successful spontaneous involution.2 Stage 3 ROP with plus disease (stage 3+) is the severe active stage that typically occurs just before detachment of the retina.3 Of 1068 studied eyes (1 randomly chosen eye per patient), 70 (6.6%) had a history of stage 3+ ROP in zone II. Yet it is remarkable that 41 (58.6%) of those eyes spontaneously went on to "favorable" visual acuity outcome by study criteria, and none of those eyes with <7 clock-hours of stage 3+ ROP had an unfavorable visual outcome. In an earlier report of the outcome of untreated eyes in the entire cohort of 4099 infants at 1 year, only 8 of 93 evaluated eyes with <5 clock-hour sectors of stage 3+ in zone II had an unfavorable fundus structure.4 So, approximately half the circumference of the eye can be affected by stage 3+ ROP in zone II with a fairly low risk of producing blindness.

Treatment of less extensive stage 3+ ROP yields illusory good results that could be cited to advance the merit of "earlier" treatment, yet such eyes would have an excellent chance of spontaneously good outcomes if the disease progressed no further under observation.5 Anecdotally improved ROP treatment results that were reported during the final decade of the 20th century likely have 2 chief explanations:

  1. More complete ablation of the peripheral retina is easier to accomplish with the laser adapted for use in infants, than with cryotherapy, and
  2. More eyes with a good prognosis were included in the denominator of the treatment group than in the CRYO-ROP study.

Although the first explanation would logically predict better results, the second explanation is impossible to evaluate without randomized controls. This is currently being done in the Early Treatment for Retinopathy of Prematurity trial.6

Earl A. Palmer, MD

Casey Eye Institute
Oregon Health & Science University
Portland, OR 97239-4197

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    ACKNOWLEDGMENTS
 
The CRYO-ROP study was supported by NEI Cooperative Agreement U10 EY05874.

FOOTNOTES

Received for publication Oct 4, 2002; Accepted Oct 4, 2002.

Reprint requests to (E.A.P.) Casey Eye Institute, Oregon Health & Science University, 3375 SW Terwilliger Blvd, Portland, OR 97239-4197. E-mail: palmere{at}ohsu.edu


    REFERENCES
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 REFERENCES
 

  1. Palmer EA, Flynn JT, Hardy RJ, et al. Incidence and early course of retinopathy of prematurity. Ophthalmology.1991; 98 :1628 –1640[Web of Science][Medline]
  2. Cryotherapy for Retinopathy of Prematurity Cooperative Group. Multicenter trial of cryotherapy for retinopathy of prematurity: natural history ROP: ocular outcome at 5 years in premature infants with birth weights less than 1251 g. Arch Ophthalmol.2002; 120 :595 –599[Abstract/Free Full Text]
  3. Cryotherapy for Retinopathy of Prematurity Cooperative Group. Multicenter trial of cryotherapy for retinopathy of prematurity: preliminary results. Pediatrics.1988; 81 :697 –706[Abstract/Free Full Text]
  4. Cryotherapy for Retinopathy of Prematurity Cooperative Group. The natural ocular outcome of premature birth and retinopathy: status at one year. Arch Ophthalmol.1994; 112 :903 –912[Abstract/Free Full Text]
  5. Palmer EA. The continuing threat of retinopathy of prematurity. Am J Ophthalmol.1996; 122 :420 –423[Web of Science][Medline]
  6. Good WV, Hardy RJ. The multicenter study of Early Treatment for Retinopathy of Prematurity (ETROP). Ophthalmology.2001; 108 :1013 –1014[CrossRef][Web of Science][Medline]

PEDIATRICS (ISSN 1098-4275). ©2003 by the American Academy of Pediatrics

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