From Casey Eye Institute (MES, BJA, DK, KLW), Oregon Health and Sciences University, Portland, Oregon; and Latin American Vision 2020 (VL), Buenos Aires, Argentina.
The authors have no financial or proprietary interest in the materials presented herein.
The authors thank Andrea Zinn, MD, for her thoughtful review of this manuscript.
Address correspondence to Kevin L. Winthrop, MD, MPH, Casey Eye Institute, 3375 SW Terwilliger Blvd., Portland, OR 97239.
Retinopathy of prematurity (ROP) is one of the leading causes of childhood blindness in the developed world.1,2 Untreated, it can lead to partial or complete retinal detachment. The effect of this outcome cannot be understated: social and learning development is highly impaired and the long-term consequences for the individual and the community can be devastating. Fortunately, blindness as a result of ROP is largely preventable with neonatal screening and treatment and by optimizing neonatology clinical practice to use appropriate oxygen therapy. High levels of blood oxygen saturation increase the risk of ROP.
Successful implementation of screening and treatment guidelines has minimized the incidence of ROP-related blindness among premature infants born in the United States and Europe.1,2 In developing countries, however, recent increases in survival rates among premature infants are associated with the emergence of ROP. This finding was noted in some regions within Latin America,3 and statistics from a 2000 World Health Organization report suggest that as many as two-thirds of children with ROP across the globe might be in Latin America.4 Differences in neonatal care (i.e., oxygen use) might explain differences in the prevalence of ROP in different countries in this region.5 For the most part, however, studies evaluating neonatal practice and the prevalence of ROP and ROP-related blindness are lacking in many regions of Latin America.
With this in mind, the authors prospectively examined premature infants from two obstetrics hospitals in Guatemala City to gain a better understanding of the prevalence of ROP and ROP-related blindness in Guatemala.
Between January and July 2007, the authors examined infants at two Guatemalan Social Security Institute hospitals: the Gynecology-Obstetrician General Hospital and the Juan Jose Arevalo Bermejo Zone 6 Hospital. The two other Guatemalan Social Security Institute hospitals in Guatemala City were not included in the current study because they have a much lower volume of live births. Hospital neonatologists were asked to refer all infants born at less than 35 weeks’ gestational age or weighing less than 2,000 g at birth for evaluation. Neonatologists also referred any infant they believed might be at higher risk for any other reason. Most infants were transported to the ophthalmology clinic only after becoming medically stable, often weeks after birth. It was unknown how many infants meeting these screening criteria were transferred or discharged before examination.
Infants were examined once or twice per week, depending on their clinical status, until vascular development in the eye had concluded. Dilated fundus examination was performed with 0.5% tropicamide and 5% phenylephrine, and proparacaine was used as a topical anesthetic. An indirect ophthalmoscope, a pediatric eyelid speculum, and a 28-diopter lens were used to assess the fundus and optic nerve head. All examinations were conducted by a pediatric ophthalmologist experienced in ROP diagnostics (MES). Clinical data were collected on each infant with a standardized clinical examination survey. All data were entered into and analyzed with Epi Info software (version 3.2; Centers for Disease Control and Prevention, Atlanta, GA). To simplify data presentation, only data from the eye with more severe ROP were reported.
Eighty-eight infants were referred for evaluation. Median gestational age was 33 weeks (range: 27 to 38 weeks), with a mean birth weight of 1,162 g (range, 652 to 2,180 g). Median corrected gestational age at examination was 39 weeks (range: 32 to 85 weeks). ROP was documented in 43 (49%) infants. Six (7%) infants born at more than 30 weeks’ gestation had plus disease (Table). No infants born weighing more 1,500 g or more had plus disease. Twenty-six (30%) had early-stage ROP, and 11 (13%) had “plus” disease that necessitated therapy. Three (3%) infants were examined too late for therapy to be initiated and were found to have stage V disease (Figure). Nine (10%) were treated with laser therapy, and two (2%) were given intravitreal bevacizumab (Avastin; Genentech, South San Francisco, CA) injection by consulting retinologists.
Table: Gestational Age and plus Disease
Figure. Examination Results Showing the Number of Infants Undergoing Examination for Retinopathy of Prematurity by Stage.
Univariate logistic regression showed that increasing gestational age at birth was significantly associated with a decreased risk of plus disease (odds ratio: 0.7; 95% confidence interval: 0.5 to 0.9; P = .01). Maternal age and fetal birth weight were not significantly correlated with the risk of ROP (P = .9 and P = .12, respectively).
The current study is the first to evaluate ROP in premature infants in Guatemala. The authors examined a consecutive sample of premature infants from two hospitals in Guatemala and found a high percentage of infants with severe ROP. In some cases, plus disease developed in infants who were born above currently recommended screening thresholds for gestational age in the United States. The current findings suggest that a formal, systematic screening program should be instituted at all Guatemala City obstetric hospitals that care for premature infants. Further research is needed to clarify optimal birth weight and gestational age screening criteria for ROP in Guatemala.
In the current study, a high percentage of neonates had ROP, and many of these infants met the criteria for ROP therapy. These findings are consistent with those from elsewhere in the developing world, especially in Latin America, where ROP is the leading preventable cause of blindness in children.4 Significant advances in medical care for pre-term and low–birth-weight infants in these regions have increased infant survival rates. Currently, ROP is believed to be the cause of 3% to 11% of childhood blindness in “highly developed” countries, 60% in “moderately developed” countries, and very low percentages in “poorly developed” countries.2 The current study likely represents an underestimate of disease burden within these two large Guatemalan hospitals during the study period because referral by neonatologists was voluntary and it was not possible to examine infants within the neonatal intensive care unit. Accordingly, some infants meeting the screening criteria may have been discharged home or to other institutions before being examined by the authors.
It is unclear why so many children screened in the current study had ROP, including many born at relatively greater gestational age. Reports from other Latin American countries suggest similar trends. In Argentina, a nationally funded study found that 24% of infants treated for ROP weighed more than 1,500 g and might not have been screened in the United States.5 Other countries with similar populations have already attempted to implement new screening criteria based on their specific populations.6 As a result, ROP screening guidelines were developed specifically for Latin America advocating screening of all infants weighing 1,750 g or less or born at 32 weeks’ gestational age or less.7 This Vision 2020 guideline also recommends that local investigators collect data specific to their region to refine these screening recommendations because the risk of ROP might vary by region and local oxygen use practices.
Prolonged use of high concentrations of inspired oxygen is a strong risk factor for ROP5,8 and might explain why some children in the current study had significant disease despite being older than 30 weeks’ gestational age. The hospital policy of the institutions included in the current study reportedly promoted target blood oxygen saturation levels of 95%, which is greater than the recommended range of 85% to 93% associated with a lower risk of ROP.7 Accordingly, future efforts to prevent ROP at these institutions should include educating neonatology staff about appropriate oxygen use in this setting.
Standardized screening has led to effective development of cryotherapy and diode laser treatments for use in preterm infants with threshold ROP. In 2003, Phan et al.9 reported on screening and treatment among 225 infants in Vietnam. They found a 75% favorable outcome rate for eyes with threshold ROP with cryotherapy treatment and only an 18.75% favorable outcome rate for untreated eyes. A 1988 multicenter randomized trial conducted by the National Eye Institute in Bethesda, Maryland,10 found that treatment reduced by approximately 50% the incidence of unfavorable outcomes in infants with threshold ROP, stage III ROP, or higher, as defined by the original International Committee on Retinopathy of Prematurity in 1984.10–16
In the current cohort of neonates, most were treated with diode laser. However, some children were treated with intravitreal bevacizumab. This treatment is neither approved nor indicated for ROP and carries the theoretical risk of inhibiting the development of normal vasculature. It is not known whether such treatment is safe. Anecdotally, the authors were told that limited access to effective laser therapy was the reason why bevacizumab therapy was used. Patients from the current study should be observed over the long term to determine treatment outcomes.
To the authors’ knowledge, the current study is the first to assess the prevalence of ROP in Guatemala. The current findings suggest the need for a follow-up, prospective study in Guatemala City to refine the ROP screening criteria for this area. For now, the findings of the current study suggest that any infant weighing less than 2,000 g or born before 37 weeks’ gestation should be examined. Unlike in the current study, all efforts should be made to examine children within neonatal care units. Neonatal oxygen therapy practices within these institutions should be evaluated simultaneously.
- Drack A. Retinopathy of prematurity. Adv Pediatr. 2006;53:211–226. doi:10.1016/j.yapd.2006.04.010 [CrossRef]
- Gilbert C, Fielder A, Dordillo L, et al. Severe retinopathy of prematurity in countries with low, moderate and high levels of development: implications for screening programmes. Pediatrics. 2005;115:e518–e525. doi:10.1542/peds.2004-1180 [CrossRef]
- Bouzas L, Bauer G, Novali L, et al. La retinopatía del prematuro en el siglo XXI en un país en desarrollo: una urgencia que debe ser resuelta. An Pediatr (Barc). 2007;66:551–558. doi:10.1157/13107388 [CrossRef]
- World Health Organization. Preventing blindness in children: report of WHO/IAPB Scientific Meeting (Unpublished document WHO/PBL/00.77).
- Dirección Nacional de Salud Materno Infantil. Retinopatía del prematuro en Servicios de Neonatología de Argentina. Arch Argent Pediatr. 2006;104:69–74.
- Vedantham V. Retinopathy of prematurity screening in the Indian population: it’s time to set our own guidelines!Indian J Ophthalmol. 2007;55:329–330. doi:10.4103/0301-4738.33816 [CrossRef]
- Vision 2020. Guidelines for ROP Screening and Treatment in Latin American Countries. Available at: http://www.v2020la.org/english/pdf/publications/GuidelinesROP.pdf.
- Tin W, Gupta S. Optimum oxygen therapy in preterm babies. Arch Dis Child Fetal Neonatal Ed. 2007;92:F143–F147. doi:10.1136/adc.2005.092726 [CrossRef]
- Phan M, Nguyen P, Reynolds J. Incidence and severity of retinopathy of prematurity in Vietnam, a developing middle-income country. J Pediatr Ophthalmol Strabismus. 2003;40:208–212.
- Fang PC, Kuo HK, Ko TY, Hwang KP, Chung MY. Retinopathy of prematurity in larger preterm infants. Am J Perinatol. 2006;23:273–277. doi:10.1055/s-2006-941454 [CrossRef]
- International Committee for the Classification of Retinopathy of Prematurity. The International Classification of Retinopathy of Prematurity revisited. Arch Ophthalmol. 2005;123:991–999.
- Chow LC, Wright KW, Sola A. Can changes in clinical practice decrease the incidence of severe retinopathy of prematurity in very low birth weight infants?Pediatrics. 2003;111:339–345. doi:10.1542/peds.111.2.339 [CrossRef]
- Fielder A, Gilbert C, Quinn G. Can ROP blindness be eliminated?Biol Neonate. 2005;88:98–100. doi:10.1159/000085296 [CrossRef]
- The International Committee for the Classification of the Late Stages of Retinopathy of Prematurity. An international classification of retinopathy of prematurity: II. The classification of retinal detachment. Arch Ophthalmol. 1987;105:906–912.
- Pérez Rodríguez J, Peralta Calvo J. Retinopatía de la prematuridad en la primera década del siglo XXI: dos caras de la misma moneda. An Pediatr (Barc). 2007;66:549–550. doi:10.1157/13107387 [CrossRef]
- The Committee for the Classification of Retinopathy of Prematurity: An International Classification of Retinopathy of Prematurity. Arch Ophthalmol. 1984;102:1130–1134.
Gestational Age and plus Diseasea
|Gestational Age in Weeks (N = 84)||No. With Plus Disease|
|27 (n = 1)||0 (0%)|
|28 (n = 7)||4 (57%)|
|29 (n = 2)||1 (50%)|
|30 (n = 5)||0 (0%)|
|31 (n = 2)||0 (0%)|
|32 (n = 14)||3 (21%)|
|33 (n = 11)||1 (9%)|
|34 (n = 18)||1 (6%)|
|35 (n = 13)||0 (0%)|
|36 (n = 6)||0 (0%)|
|37 (n = 0)||0 (0%)|
|38 (n = 2)||1 (50%)|