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Special Article |

Retinopathy of Prematurity: Do We Still Have a Problem?  The Charles L. Schepens Lecture FREE

William Tasman, MD
[+] Author Affiliations

Author Affiliations: Department of Ophthalmology, Jefferson Medical College, Thomas Jefferson University, and Wills Eye Hospital, Philadelphia, Pennsylvania.


Arch Ophthalmol. 2011;129(8):1083-1086. doi:10.1001/archophthalmol.2011.192.
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Published online

Objective To assess the present-day prevalence of retinopathy of prematurity (ROP) worldwide.

Methods A search of the literature was conducted to better define the worldwide experience with ROP. An interview was also conducted with 2 schools for the blind, Overbrook in Philadelphia, Pennsylvania, and Perkins in Watertown, Massachusetts. The study also is based on personal experience with ROP over the last 49 years.

Results Worldwide, the prevalence of ROP is on the rise in developing countries, and some of those ROP-affected premature infants are heavier than 1500 g. In western countries, extremely low-birth-weight infants (≤1000 g) are also surviving. Currently, the Overbrook School for the Blind has 11 of 55 children between the ages of 3 and 5 years with ROP (20%). The Perkins School has 34 of 200 children from birth to age 3 years with ROP (17%). During 2009, 47 babies had laser treatment for ROP in the neonatal intensive care unit of Jefferson Medical College by physicians from Wills Eye Hospital. Twenty-four infants had been identified in a screening of 591 patients (4.1%). The other 23 had been referred in for treatment. In 2009, we had 187 outpatient visits related to ROP ranging from 6 months to 67 years of age.

Conclusions Because more and more extreme low-birth-weight infants are surviving in western countries and because of the rising numbers of surviving premature infants in emerging nations, we may be on the verge of an ROP epidemic.

Figures in this Article

I am most grateful to the Retina Research Foundation, the Schepens International Society, and Alice McPherson for this magnificent award. Clearly, Charles Schepens was an icon, not only of the 20th century, but for all time in ophthalmology. I was fortunate enough to have a fellowship with him from 1961 to 1962 in Boston at the Massachusetts Eye and Ear Infirmary. During that time, I enjoyed a learning experience like none I had had before. Dr Schepens was a role model for how to care for patients, and the lessons I learned from him have stood me in good stead over the years. His contribution of binocular indirect ophthalmoscopy and his surgical innovations for retinal detachment raised the cure rate for that condition from somewhere between 25% and 40% to close to 90%.

A word, too, about Mrs Schepens. In a conversation I had with her at a party one time, I commented on what a hard worker Dr Schepens was and the long hours that he worked. Her reply was that it is important for a wife to understand that if a man loves what he is doing she should be happy for him.

I might mention, as well, that my initial interest in retinopathy of prematurity (ROP) was stimulated by Dr Schepens. While in Boston, I was fortunate enough to assist him in repairing retinal detachments on patients who had a history and clinical signs of ROP. I was able to carry that interest forward.

First described by Theodore Terry in 1942,1 ROP, then known as retrolental fibroplasia, became a major cause of blindness in children in the United States. Actually, the first recognized case was seen in July 1940 by Drs Stewart Clifford, Paul Chandler, and Frederic Verhoeff, who then referred the infant to Dr Terry. Retinopathy of prematurity often resulted from the practice at that time of giving a high percentage of oxygen to low-birth-weight infants. Ultimately, a 40% limit of oxygen was recommended, and the incidence of blindness from ROP decreased. However, many more infants died, and in those infants who survived, the prevalence of cerebral palsy increased.2

Today, it is understood that low birth weight and low gestational age are significant contributors to ROP. At present, the condition is more prevalent in the industrialized world but is rising quickly in emerging countries. With our better understanding of ROP, one would think that the number of blind infants might be decreasing. However, even extremely low-birth-weight infants (≤1000 g) are now surviving, as well as premature infants of 23 weeks' gestation. Thus, it is probable that we will see even more infants with ROP than in the past.

According to World Health Organization criteria, there were 1.5 million children worldwide who were blind in 1999.3 Only a small percentage of cases were due to ROP. Over the last 10 years, however, as indicated earlier, the proportion of blindness as a result of ROP had varied greatly among countries. In ranking blindness from ROP by country, the United States is eighth. Sweden is number 2, and the Eastern European countries of Bulgaria and Lithuania, for example, rank 56 and 67, respectively.4

In a personal interview with the Overbrook School for the Blind in Philadelphia, Pennsylvania, I learned that 11 of 55 children between the ages of 3 and 5 years, or roughly 20%, are in the school because of ROP. In a similar interview with the Perkins School for the Blind in Watertown, Massachusetts, 34 of 200 children from birth to age 3 years, or 17%, had ROP. Thus, ROP is still very much with us.

In industrialized countries, some degree of ROP may develop in 72% of infants weighing less than 1000 g at birth, and subsequent blindness can be as high as about 8% to 10%.5 In general, about 60% of low-birth-weight infants can be expected to develop some degree of ROP.5

In our experience at Wills Eye Hospital and Jefferson Medical College, both in Wyndmoor, Pennsylvania, 47 infants had laser treatment for ROP in 2009. Twenty-three of these patients had been referred to us, and 24 were identified in a screening of 591 patients, for a 4.1% incidence.

Studies in Mongolia, Malaysia, and Latin America are detecting more cases of ROP. In Malaysia, for example, examination of 294 children in whom the anatomical site of abnormality could be identified revealed that 20, or about 7%, had ROP.4 Although the children had impaired vision of varying degrees, 150 children had navigational vision. According to a 2005 report,3 two-thirds of the 50 000 children known to be blind from ROP worldwide are in Latin America. The numbers may have changed over the last 5 years. However, when the study was done in Lima, Peru, which at that time was a city of 8 million inhabitants, there was only 1 ophthalmologist who single-handedly did ROP screening for the whole city.

The mean premature birth weights of infants in highly developed countries range between 737 and 763 g, and the mean premature birth weights of infants in emerging countries range from 903 to 1527 g. Gestational ages of infants in highly developed countries range from 25.3 to 25.6 weeks, compared with 26.3 to 33.5 weeks in emerging countries.4

In addition, larger, more mature infants are developing severe ROP in countries with lower or modest levels of development compared with those in highly developed countries. The reasons for this are probably multifactorial, but unmonitored oxygen is likely a contributing factor. This is similar to what occurred in the 1940s and 1950s when ROP was emerging in the United States.2 However, in countries such as India and Ethiopia, conditions other than ROP are mainly responsible for blindness.69

Finally, the indications for treatment have changed. In the 1980s, 6% of patients with ROP reached the ROP threshold as defined in the Cryotherapy for Retinopathy of Prematurity Study at that time.10 However, since the Early Treatment for Retinopathy of Prematurity Study results were reported, 9% of patients reached type 1 ROP, the new threshold, requiring earlier intervention than indicated in the Cryotherapy for Retinopathy of Prematurity Study.11

It is important to keep in mind that ROP is a lifetime disease.12 In 2009, our mid-Atlantic retina practice had 187 visits from patients with ROP, with the patients ranging in age from 6 months to 67 years. The mean age was 28 years, and the median age was 22 years. Only 28 of the 187 visits were for patients younger than 5 years.

Whether treated or untreated in infancy, the retinas in adults who were premature as infants can have a different appearance than in those adults who were full-term infants. For example, dragged retina is a common finding, but less well appreciated is the finding that the mean foveal thickness of the retina in patients with ROP is often greater with loss of the foveal pit than it is patients who were full-term infants.13

Myopia is also prevalent among adults with ROP. In an examination of 43 eyes of adult patients with ROP, 39 (90.7%) were found to be myopic.14 In a non-ROP population, the prevalence was only 25%.15,16 The myopia in adults with ROP is often not axial but, rather, is due to a shorter radius of corneal curvature making for a steeper corner.14

Adults with ROP may also develop retinal detachments. For example, we have seen and treated patients in their 40s and 50s for retinal detachment. In April 2008, a 54-year-old woman, who had had a scleral buckle for a rhegmatogenous detachment in her only eye 25 years before, was seen because of a drop in vision (Figure 1). She had developed a vitreoretinal traction syndrome, which had reduced visual acuity to 20/50 compared with a previous acuity of 20/25. Neither the patient nor I was anxious to operate on this only eye, so we observed it, and by March 2010, the vitreoretinal traction had spontaneously released and visual acuity returned to 20/25 (Figure 2).

Place holder to copy figure label and caption
Graphic Jump Location

Figure 1. Nasal scleral buckle performed 25 years earlier on a 1-eyed 59-year-old woman who weighed 0.9 kg, 56 g at birth.

Place holder to copy figure label and caption
Graphic Jump Location

Figure 2. A, Vitreoretinal traction syndrome in the 59-year-old woman shown in Figure 1. B, In August 2008, her visual acuity was 20/50. In October 2009, there was partial release of vitreoretinal traction syndrome. C, In March 2010, there was release of vitreoretinal traction syndrome with a return to a visual acuity of 20/25.

Another finding is that many patients with ROP develop cataracts, which are usually nuclear and/or posterior subcapsular. Although there is no scientific evidence to support it, I have been impressed with the number of postcataract eyes that develop a hazy posterior capsule within the first few months postoperatively and the few that have even developed anterior capsular phimosis (Figure 3).

Place holder to copy figure label and caption
Graphic Jump Location

Figure 3. Images of the eye of an adult female with retinopathy of prematurity revealing anterior capsule phimosis 6 weeks after cataract surgery (A) and after Nd:YAG laser treatment to open the anterior capsule (B).

So, what can we expect as we progress further into the 21st century? Laser therapy has proved extremely effective as treatment for type 1 threshold ROP, with a success rate of 91% to 95% except for some zone 1 eyes.17

Also, bevacizumab (Avastin; Genentech, San Francisco, California), an anti–vascular endothelial growth factor (VEGF) therapy, is now available. It has been demonstrated that when oxygen is increased, the amount of VEGF produced is decreased, and when it is lowered, the VEGF again increases. Because bevacizumab can moderate the amount of VEGF, it is now being used by some as a primary treatment in type 1 ROP. Encouraging results have been reported by Quiroz-Mercado et al18 in Mexico and Mintz-Hittner and Kuffel19 in Texas.

Although the treatment appears to be safe,1820 it would seem prudent to approach this new therapy with caution. In the early days of retrolental fibroplasia, it was felt that increasing oxygen might help respiratory distress, but, instead, it increased the number of children who became blind from ROP.2 Later, corticosteroids were used in an attempt to remove premature infants from ventilators earlier, and this led to an increase in cerebral palsy. Referring to the retrolental fibroplasia epidemic in the 1940s and 1950s, William A. Silverman pointed out “that scientific rules of evidence must be satisfied before any new technique in management of premature infants was used in teaching centers.”21

For example, the current dosage of bevacizumab for intravitreal injection in ROP is 0.625 mg (0.025 mL), which is half of the dosage used for adults. However, a comparison of vitreous cavity volumes between 2 postmortem eyes from a premature infant and 1 postmortem eye from an adult showed that the volumes of the postmortem eyes from the premature infant were less than one-third that of the postmortem eye from the adult (Figure 4). This raises the question of whether the dosage of bevacizumab could be lowered.

Place holder to copy figure label and caption
Graphic Jump Location

Figure 4. Comparison of vitreous cavity volumes (V) between 2 postmortem eyes from a premature infant and 1 postmortem eye from an adult harboring a melanoma. The volume of the vitreous cavity in each of the eyes of the premature infant is less than one-third of the vitreous cavity volume of the adult eye (courtesy of Ralph Eagle, MD). ROP indicates retinopathy of prematurity.

A recent study22 compared the target range of oxygen saturation of from 85% to 90% with that from 91% to 95% to determine which range of oxygen saturation would most likely minimize retinopathy without adverse effects. The lower range of oxygen saturation (85%-90%) resulted in decreased ROP but increased mortality.

Avery and colleagues23 have shown that, in patients with diabetic retinopathy, a systemic effect is validated by a response in the fellow eye after bevacizumab injection into the eye that requires treatment. Sears24 and Sears et al25 have suggested dose adjustment to match the mean concentration of vitreous VEGF, something with which I agree, and they have also shown that lower oxygen targets at an early gestational age and higher oxygen targets at an older gestational age decrease the incidence and severity of ROP.

Thus, for the present, I personally would consider treatment with bevacizumab in ROP as an adjunct to laser therapy in type 1 eyes that do not react appropriately to laser, in pupils that do not dilate because of iris engorgement, and in tunica vasculosa lentis (Figure 5). But, as Darlow and colleagues26 point out, a complete understanding of adverse effects is essential before there is widespread implementation of this promising therapy.

Place holder to copy figure label and caption
Graphic Jump Location

Figure 5. Persistent tunica vasculosa lentis in the eye of a premature infant requiring laser treatment for threshold retinopathy of prematurity.

In concluding, I would like to paraphrase Francis Church's response in The New York Sun to Virginia O’Hanlon's query about Santa Claus. Yes, Virginia, we still have a problem with ROP.

Correspondence: William Tasman, MD, Wills Eye Hospital, 840 Walnut St, Philadelphia, PA 19107 (wst1@ureach.com).

Submitted for Publication: September 27, 2010; final revision received November 23, 2010; accepted November 23, 2010.

Financial Disclosure: None reported.

Terry TL. Extreme prematurity and fibroblastic overgrowth of persistent vascular sheath behind each crystalline lens, I: preliminary report.  Am J Ophthalmol. 1942;25:203-204
Crosse VM, Evans PJ. Prevention of retrolental fibroplasia.  AMA Arch Ophthalmol. 1952;48(1):83-87
PubMed   |  Link to Article
Steinkuller PG, Du L, Gilbert C, Foster A, Collins ML, Coats DK. Childhood blindness.  J AAPOS. 1999;3(1):26-32
PubMed   |  Link to Article
Gilbert C, Fielder A, Gordillo L,  et al; International NO-ROP Group.  Characteristics of infants with severe retinopathy of prematurity in countries with low, moderate, and high levels of development: implications for screening programs.  Pediatrics. 2005;115(5):e518-e525
PubMed   |  Link to Article
Gilbert C. Retinopathy of prematurity: epidemiology.  J Community Eye Health. 1997;10(22):22-24http://www.cehjournal.org/0953-6833/10/jceh_10_22_022.html. Accessed May 27, 2011.
Reddy SC, Tan BC. Causes of childhood blindness in Malaysia: results from a national study of blind school students.  Int Ophthalmol. 2001;24(1):53-59
PubMed   |  Link to Article
Haddad MA, Sei M, Sampaio MW, Kara-José N. Causes of visual impairment in children: a study of 3,210 cases.  J Pediatr Ophthalmol Strabismus. 2007;44(4):232-240
PubMed
Rahi JS, Sripathi S, Gilbert CE, Foster A. Childhood blindness in India: causes in 1318 blind school students in nine states.  Eye (Lond). 1995;9(pt 5):545-550
PubMed   |  Link to Article
Kello AB, Gilbert C. Causes of severe visual impairment and blindness in children in schools for the blind in Ethiopia.  Br J Ophthalmol. 2003;87(5):526-530
PubMed   |  Link to Article
Cryotherapy for Retinopathy of Prematurity Cooperative Group.  Multicenter trial of cryotherapy for retinopathy of prematurity: Snellen visual acuity and structural outcome at 5 1/2 years after randomization.  Arch Ophthalmol. 1996;114(4):417-424
PubMed   |  Link to Article
Good WV, Hardy RJ, Dobson V,  et al; Early Treatment for Retinopathy of Prematurity Cooperative Group.  The incidence and course of retinopathy of prematurity: findings from the Early Treatment for Retinopathy of Prematurity Study.  Pediatrics. 2005;116(1):15-23
PubMed   |  Link to Article
Tasman W, Patz A, McNamara JA, Kaiser RS, Trese MT, Smith BT. Retinopathy of prematurity: the life of a lifetime disease.  Am J Ophthalmol. 2006;141(1):167-174
PubMed   |  Link to Article
Baker PS, Tasman W. Optical coherence tomography imaging of the fovea in retinopathy of prematurity.  Ophthalmic Surg Lasers Imaging. 2010;41(2):201-206
PubMed   |  Link to Article
Baker PS, Tasman W. Myopia in adults with retinopathy of prematurity.  Am J Ophthalmol. 2008;145(6):1090-1094
PubMed   |  Link to Article
 US Census Bureau Estimates. US Census Bureau Web site. http://www.census.gov/popest/estimates.html. Accessed May 27, 2011
 US Census Bureau International Data Base (IDB). http://www.census.gov/ipc/www/idb/. Accessed May 27, 2011
Hurley BR, McNamara JA, Fineman MS,  et al.  Laser treatment for retinopathy of prematurity: evolution in treatment technique over 15 years.  Retina. 2006;26(7):(suppl)  S16-S17
PubMed   |  Link to Article
Quiroz-Mercado H, Ustariz-González O, Martinez-Castellanos MA, Covarrubias P, Dominguez F, Sanchez-Huerta V. Our experience after 1765 intravitreal injections of bevacizumab: the importance of being part of a developing story.  Semin Ophthalmol. 2007;22(2):109-125
PubMed   |  Link to Article
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. 2008;28(6):831-838
PubMed   |  Link to Article
Sakurai K, Akiyama H, Shimoda Y, Yoshida I, Kurabayashi M, Kishi S. Effect of intravitreal injection of high-dose bevacizumab in monkey eyes.  Invest Ophthalmol Vis Sci. 2009;50(10):4905-4916
PubMed   |  Link to Article
Silverman WA. Retrolental Fibroplasia: A Modern Parable. New York, NY: Grune & Stratton; 1980
SUPPORT Study Group of the Eunice Kennedy Shriver NICHD Neonatal Research Network.  Target ranges of oxygen saturation in extremely preterm infants.  N Engl J Med. 2010;362(21):1959-1969
PubMed   |  Link to Article
Avery RL, Pearlman J, Pieramici DJ,  et al.  Intravitreal bevacizumab (Avastin) in the treatment of proliferative diabetic retinopathy.  Ophthalmology. 2006;113(10):1695.e1-1695.e15
PubMed   |  Link to Article
Sears JE. Anti-vascular endothelial growth factor and retinopathy of prematurity.  Br J Ophthalmol. 2008;92(11):1437-1438
PubMed   |  Link to Article
Sears JE, Pietz J, Sonnie C, Dolcini D, Hoppe G. A change in oxygen supplementation can decrease the incidence of retinopathy of prematurity.  Ophthalmology. 2009;116(3):513-518
PubMed   |  Link to Article
Darlow BA, Gilbert C, Quinn GE,  et al.  Promise and potential pitfalls of anti-VEGF drugs in retinopathy of prematurity.  Br J Ophthalmol. 2009;93(7):986
PubMed   |  Link to Article

Figures

Place holder to copy figure label and caption
Graphic Jump Location

Figure 1. Nasal scleral buckle performed 25 years earlier on a 1-eyed 59-year-old woman who weighed 0.9 kg, 56 g at birth.

Place holder to copy figure label and caption
Graphic Jump Location

Figure 2. A, Vitreoretinal traction syndrome in the 59-year-old woman shown in Figure 1. B, In August 2008, her visual acuity was 20/50. In October 2009, there was partial release of vitreoretinal traction syndrome. C, In March 2010, there was release of vitreoretinal traction syndrome with a return to a visual acuity of 20/25.

Place holder to copy figure label and caption
Graphic Jump Location

Figure 3. Images of the eye of an adult female with retinopathy of prematurity revealing anterior capsule phimosis 6 weeks after cataract surgery (A) and after Nd:YAG laser treatment to open the anterior capsule (B).

Place holder to copy figure label and caption
Graphic Jump Location

Figure 4. Comparison of vitreous cavity volumes (V) between 2 postmortem eyes from a premature infant and 1 postmortem eye from an adult harboring a melanoma. The volume of the vitreous cavity in each of the eyes of the premature infant is less than one-third of the vitreous cavity volume of the adult eye (courtesy of Ralph Eagle, MD). ROP indicates retinopathy of prematurity.

Place holder to copy figure label and caption
Graphic Jump Location

Figure 5. Persistent tunica vasculosa lentis in the eye of a premature infant requiring laser treatment for threshold retinopathy of prematurity.

Tables

References

Terry TL. Extreme prematurity and fibroblastic overgrowth of persistent vascular sheath behind each crystalline lens, I: preliminary report.  Am J Ophthalmol. 1942;25:203-204
Crosse VM, Evans PJ. Prevention of retrolental fibroplasia.  AMA Arch Ophthalmol. 1952;48(1):83-87
PubMed   |  Link to Article
Steinkuller PG, Du L, Gilbert C, Foster A, Collins ML, Coats DK. Childhood blindness.  J AAPOS. 1999;3(1):26-32
PubMed   |  Link to Article
Gilbert C, Fielder A, Gordillo L,  et al; International NO-ROP Group.  Characteristics of infants with severe retinopathy of prematurity in countries with low, moderate, and high levels of development: implications for screening programs.  Pediatrics. 2005;115(5):e518-e525
PubMed   |  Link to Article
Gilbert C. Retinopathy of prematurity: epidemiology.  J Community Eye Health. 1997;10(22):22-24http://www.cehjournal.org/0953-6833/10/jceh_10_22_022.html. Accessed May 27, 2011.
Reddy SC, Tan BC. Causes of childhood blindness in Malaysia: results from a national study of blind school students.  Int Ophthalmol. 2001;24(1):53-59
PubMed   |  Link to Article
Haddad MA, Sei M, Sampaio MW, Kara-José N. Causes of visual impairment in children: a study of 3,210 cases.  J Pediatr Ophthalmol Strabismus. 2007;44(4):232-240
PubMed
Rahi JS, Sripathi S, Gilbert CE, Foster A. Childhood blindness in India: causes in 1318 blind school students in nine states.  Eye (Lond). 1995;9(pt 5):545-550
PubMed   |  Link to Article
Kello AB, Gilbert C. Causes of severe visual impairment and blindness in children in schools for the blind in Ethiopia.  Br J Ophthalmol. 2003;87(5):526-530
PubMed   |  Link to Article
Cryotherapy for Retinopathy of Prematurity Cooperative Group.  Multicenter trial of cryotherapy for retinopathy of prematurity: Snellen visual acuity and structural outcome at 5 1/2 years after randomization.  Arch Ophthalmol. 1996;114(4):417-424
PubMed   |  Link to Article
Good WV, Hardy RJ, Dobson V,  et al; Early Treatment for Retinopathy of Prematurity Cooperative Group.  The incidence and course of retinopathy of prematurity: findings from the Early Treatment for Retinopathy of Prematurity Study.  Pediatrics. 2005;116(1):15-23
PubMed   |  Link to Article
Tasman W, Patz A, McNamara JA, Kaiser RS, Trese MT, Smith BT. Retinopathy of prematurity: the life of a lifetime disease.  Am J Ophthalmol. 2006;141(1):167-174
PubMed   |  Link to Article
Baker PS, Tasman W. Optical coherence tomography imaging of the fovea in retinopathy of prematurity.  Ophthalmic Surg Lasers Imaging. 2010;41(2):201-206
PubMed   |  Link to Article
Baker PS, Tasman W. Myopia in adults with retinopathy of prematurity.  Am J Ophthalmol. 2008;145(6):1090-1094
PubMed   |  Link to Article
 US Census Bureau Estimates. US Census Bureau Web site. http://www.census.gov/popest/estimates.html. Accessed May 27, 2011
 US Census Bureau International Data Base (IDB). http://www.census.gov/ipc/www/idb/. Accessed May 27, 2011
Hurley BR, McNamara JA, Fineman MS,  et al.  Laser treatment for retinopathy of prematurity: evolution in treatment technique over 15 years.  Retina. 2006;26(7):(suppl)  S16-S17
PubMed   |  Link to Article
Quiroz-Mercado H, Ustariz-González O, Martinez-Castellanos MA, Covarrubias P, Dominguez F, Sanchez-Huerta V. Our experience after 1765 intravitreal injections of bevacizumab: the importance of being part of a developing story.  Semin Ophthalmol. 2007;22(2):109-125
PubMed   |  Link to Article
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. 2008;28(6):831-838
PubMed   |  Link to Article
Sakurai K, Akiyama H, Shimoda Y, Yoshida I, Kurabayashi M, Kishi S. Effect of intravitreal injection of high-dose bevacizumab in monkey eyes.  Invest Ophthalmol Vis Sci. 2009;50(10):4905-4916
PubMed   |  Link to Article
Silverman WA. Retrolental Fibroplasia: A Modern Parable. New York, NY: Grune & Stratton; 1980
SUPPORT Study Group of the Eunice Kennedy Shriver NICHD Neonatal Research Network.  Target ranges of oxygen saturation in extremely preterm infants.  N Engl J Med. 2010;362(21):1959-1969
PubMed   |  Link to Article
Avery RL, Pearlman J, Pieramici DJ,  et al.  Intravitreal bevacizumab (Avastin) in the treatment of proliferative diabetic retinopathy.  Ophthalmology. 2006;113(10):1695.e1-1695.e15
PubMed   |  Link to Article
Sears JE. Anti-vascular endothelial growth factor and retinopathy of prematurity.  Br J Ophthalmol. 2008;92(11):1437-1438
PubMed   |  Link to Article
Sears JE, Pietz J, Sonnie C, Dolcini D, Hoppe G. A change in oxygen supplementation can decrease the incidence of retinopathy of prematurity.  Ophthalmology. 2009;116(3):513-518
PubMed   |  Link to Article
Darlow BA, Gilbert C, Quinn GE,  et al.  Promise and potential pitfalls of anti-VEGF drugs in retinopathy of prematurity.  Br J Ophthalmol. 2009;93(7):986
PubMed   |  Link to Article

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