From Ophthalmic Associates, Anchorage, Alaska.
Dr. Arnold is on the governing board of a company, Glacier Medical Software, Inc., that develops software (“ROP-Check”) to schedule, monitor, and record neonatal intensive care unit retinopathy of prematurity examinations.
Address correspondence to Robert W. Arnold, MD, Ophthalmic Associates, 542 West Second Avenue, Anchorage, AK 99501-2242.
Despite advances in neonatal intensive care units and options for treatment, retinopathy of prematurity remains a significant etiology of childhood blindness in the United States and worldwide. Risk factors that predispose an infant to threshold retinopathy of prematurity (ROP) include early gestational age, low birth weight, Pacific race,1 need for supplemental ventilation, intraventricular hemorrhage, birth remote from a tertiary care neonatal intensive care unit, and poor prenatal care.2 Many infants who progress to bilateral threshold ROP are sufficiently treated with fairly symmetric numbers of laser burns or cryotherapy freezes, but some infants have asymmetric progression of ROP.
This brief report describes infants with asymmetric ROP associated with moderate and marked optic nerve hypoplasia.
In this observational study with Institutional Review Board approval from Providence Hospital, all infants with a birth weight of less than 1,500 grams in Alaska’s tertiary care neonatal intensive care unit from September 1989 through November 2003 were examined by one observer (RWA) and data were collected prospectively. Threshold was defined by CRYO-ROP criteria.
These infants were observed for at least 1 year after discharge from the neonatal intensive care unit with comprehensive ophthalmic examinations.
A 23-week gestational age, 590-gram birth weight Asian female infant progressed to threshold posterior ROP in the right eye by 33 weeks of gestational age. The anterior extent of blood vessel progression was just sufficient to span the view in a 30-diopter condensing lens with the small optic nerve localized to one side. The left eye was subthreshold and more peripherally developed; 109 “safety” burns were directed to the temporal periphery (3 clock hours of stage 3). There was no history of antenatal ethanol or drug exposure. Diode laser treatment (928 burns) was delivered to the right eye. At that time, and confirmed in subsequent years with examination under anesthesia associated with sensory esotropia, the right eye had marked optic nerve hypoplasia (Figure). Refractive error at 1 year of age was −3.00 in the right eye and +4.00 +1.00 × 90 in the left eye.
Figure. Chart Drawings and Retinopathy of Prematurity Classification for Serial Weekly Examinations for Case 1. Note the Posterior Extent of Retinopathy of Prematurity in the Right Eye and the Drawing of Relative Optic Nerve Head Sizes on the Bottom of the Page Lateral to Each Eye’s Retinal Drawing.
A 25-week gestational age, 750-gram birth weight white female infant with prenatal ethanol3 and tetrahydrocannabinol exposure progressed to asymmetric threshold by 37 weeks of gestational age. She received diode laser treatment with 2,013 burns in the right eye and 1,113 burns in the left eye. The nerves were minimally pale and the right eye was relatively hypoplastic with a diameter of 75% of the left eye.
This patient was not treated by the author. A 25-week gestational age, 690-gram black male twin infant was noted to have nerve asymmetry but only progressed to stage 2, zone 2 with minimal plus disease. After 1 year of age, the cycloplegic refraction was −1.00 in the right eye with 0.3 normal colored optic nerve cup, whereas the left eye was −7.00 diopters with a smaller 0.8 cup and subtle far-temporal tractional changes.4 For significant sensory esotropia, this patient underwent examination under anesthesia and bilateral medial rectus muscle recession. Intraocular pressure remained normal by Tonopen (Reichert Ophthalmic Instruments, Depew, NY) and corneal diameters were symmetric. His 670-gram birth weight twin with symmetric nerve heads had unilateral diode laser treatment.
This patient was not treated by the author. A 26-week gestational age 1,050-gram birth weight Native female infant did not progress to threshold ROP but developed stage 4 intraventricular hemorrhage. For an adduction deficit and large sensory exotropia, she underwent examination under anesthesia and lateral rectus recessions. The right optic nerve was 20% normal diameter associated with an-isometropic refraction of −3.00 sphere in the right eye and +1.75 +3.00 × 115 in the left eye. There were slight temporal retinal pigment epithelium changes in the right eye but no macular drag. Asymmetric, subthreshold ROP was suspected.
From November 2003 through December 2005, an additional 120 infants with a birth weight of less than 1,500 grams were examined for ROP5 and 14 were treated according to revised treatment threshold.6,7 None of these infants was noted to have significant optic nerve hypoplasia or atrophy.
Four infants were noted to have evidence of optic nerve hypoplasia or atrophy. Of these, two progressed to treatment threshold as diagrammed in the serial clinical record (Figure). Each was noted to have substantially more peripheral avascular retina.
Two infants with markedly asymmetric ROP had farther posterior disease in the eye with optic nerve hypoplasia. Two other infants with moderate optic nerve hypoplasia did not progress to threshold at that time but had asymmetric retinal outcomes suggestive of asymmetric ROP severity. The observed hyporetinal development with small optic nerves suggested worse ROP. Not much has been published on an association between these conditions,8 but optic nerve hypoplasia appears more common in prematurity.9,10 Stunted prenatal retinal arterial development, selective oxygen-associated vaso-obliteration, or both may accompany optic nerve hypoplasia. No patients with bilateral severe optic nerve hypoplasia associated with marked prematurity were observed in this series.
Optic nerve hypoplasia can be associated with photoreceptor and ganglion cell loss or with central nervous system disease. Retinal development, characterized by normal posterior poles and maculae, was normal in all four cases, but case 4 had marked intraventricular hemorrhage.
Two of the most common etiologies for pediatric blindness are ROP and optic nerve hypoplasia.11,12 When these occur simultaneously, the eye has poor visual potential but stable retinal architecture can be preserved with sufficient peripheral ablation. Optic nerve hypodevelopment may place an infant at high risk for strabismus and high myopia.13
Optic nerve hypoplasia, similar to residual ROP, is a significant enough pediatric disease and cause of blindness to deserve its own International Classification of Diseases (ICD) code. Unfortunately, optic nerve hypoplasia has an ICD code lumped with all other genetic developmental anomalies of the posterior segment of the eye (743.57) and therefore cannot be as accurately tracked as other uniquely coded and environmentally influenced birth defects. Early development of the retinal vessels14 can be associated with the optic nerve and children with small nerves have relatively more avascular retina at a critical period and therefore are at higher risk for adverse ROP sequelae. The post-natal development of the optic nerve head may also be associated with asymmetry of the ocular anatomy noted with ROP, even accounting for relative minification associated with asymmetry of refractive error in ROP.
- : Lang DM, Blackledge J, Arnold RW. Is Pacific race a retinopathy of prematurity risk factor?Arch Pediatr Adolesc Med. 2005;159:771–773. doi:10.1001/archpedi.159.8.771 [CrossRef]
- : Palmer EA, Flynn JT, Hardy RJ, et al. . Incidence and early course of retinopathy of prematurity. The Cryotherapy for Retinopathy of Prematurity Cooperative Group. Ophthalmology. 1991;98:1628–1640.
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- : Dutton GN. Congenital disorders of the optic nerve: excavations and hypoplasia. Eye. 2004;18:1038–1048. doi:10.1038/sj.eye.6701545 [CrossRef]
- : International Committee for the Classification of Retinopathy of Prematurity. The International Classification of Retinopathy of Prematurity revisited. Arch Ophthalmol. 2005;123:991–999.
- : 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;121:1684–1694.
- : 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;120:1470–1476.
- : 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. 1998;82:1246–1248.
- : Tornqvist K, Ericsson A, Kallen B. Optic nerve hypoplasia: risk factors and epidemiology. Acta Ophthalmol Scand. 2002;80:300–304. doi:10.1034/j.1600-0420.2002.800313.x [CrossRef]
- : Hellström A, Hård AL, Svensson E, Niklasson A. Ocular fundus abnormalities in children born before 29 weeks of gestation: a population-based study. Eye. 2000;14:324–329.
- : Mets MB. Childhood blindness and visual loss: an assessment at two institutions including a “new” cause. Trans Am Ophthalmol Soc. 1999;97:653–696.
- : Blohme J, Tornqvist K. Visual impairment in Swedish children: III. Diagnoses. Acta Ophthalmol Scand. 1997;75:681–687.
- : Garcia-Valenzuela E, Kaufman LM. High myopia associated with retinopathy of prematurity is primarily lenticular. J AAPOS. 2005;9:121–128. doi:10.1016/j.jaapos.2004.12.018 [CrossRef]
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