A small foveal avascular zone may be an historic mark of prematurity.

OBJECTIVE: To compare in children the area and diameter of the foveal avascular zone (FAZ) of former preterm infants, when no significant retinopathy of prematurity (ROP) developed, to the area and diameter of the FAZ of former term infants. DESIGN: Retrospective observational case series and literature review. PARTICIPANTS: Forty-nine children (39 former preterm infants and 10 former term infants) between the ages of 1 and 17 years had fluorescein angiograms. All of these children had been appropriate weight for gestational age at birth and had no genetic disorders. Neither eye of any of these children had any macular ectopia or vessel traction, had been treated for active ROP, had developed active ROP >stage 3 mild, or had any refractive error > +/- five diopters. Every child had a visual acuity of 20/40 or better in both eyes. METHODS: The area and greatest diameter of the FAZ were measured using digital image analysis of masked fundus fluorescein angiograms. Variables of gender, race, multiple birth, gestational age, birth weight, ROP stage, age, and refraction at the time of fluorescein angiography, and final visual acuity were recorded. RESULTS: Increasing FAZ area and greatest diameter correlated significantly with increasing gestational age and birth weight: FAZ area (microm2) versus gestational age (weeks) (R/F/P = 0.88/166.70/<0.0001); FAZ greatest diameter (microm) versus gestational age (weeks) (R/F/P = 0.87/151.10/<0.0001); FAZ area (micro/m2) versus birth weight (g) (R/F/P = 0.88/167.06/<0.0001); and FAZ greatest diameter (microm) versus birth weight (g) (R/F/P = 0.87/148.74/ <0.0001). A small or absent FAZ was found in all former preterm infants who had been < or = 30 weeks gestational age or had weighed < or = 1100 g at birth. A normal FAZ was present in all children who had been > or = 36 weeks gestational age or had weighed > or = 2650 g at birth. None of the other parameters studied correlated with FAZ area or greatest diameter. CONCLUSION: This study provides evidence that the FAZ in developing humans is initially densely vascularized with a fine meshwork of inner retinal vessels during vasculogenesis. This vascular meshwork undergoes regression by apoptosis in all infants > or = 36 weeks gestational age at birth to form a normal FAZ, but apoptosis almost never occurs in preterm infants < or = 30 weeks gestational age at birth. Although there is no effect on final visual acuity, a small or absent FAZ may be an historic mark of prematurity.

Peripheral retinopathy in offspring of carriers of Norrie disease gene mutations. Possible transplacental effect of abnormal Norrin.

BACKGROUND: The Norrie disease (ND) gene (Xp11.3) (McKusick 310600) consists of one untranslated exon and two exons partially translated as the Norrie disease protein (Norrin). Norrin has sequence homology and computer-predicted tertiary structure of a growth factor containing a cystine knot motif, which affects endothelial cell migration and proliferation. Norrie disease (congenital retinal detachment), X-linked primary retinal dysplasia (congenital retinal fold), and X-linked exudative vitreoretinopathy (congenital macular ectopia) are allelic disorders. METHODS: Blood was drawn for genetic studies from members of two families to test for ND gene mutations. Sixteen unaffected family members were examined ophthalmologically. If any retinal abnormality were identified, fundus photography and fluorescein angiography was performed. RESULTS: Family A had ND (R109stp), and family B had X-linked exudative vitreoretinopathy (R121L). The retinas of 11 offspring of carrier females were examined: three of seven carrier females, three of three otherwise healthy females, and one of one otherwise healthy male had peripheral inner retinal vascular abnormalities. The retinas of five offspring of affected males were examined: none of three carrier females and none of two otherwise healthy males had this peripheral retinal finding. CONCLUSIONS: Peripheral inner retinal vascular abnormalities similar to regressed retinopathy of prematurity were identified in seven offspring of carriers of ND gene mutations in two families. These ophthalmologic findings, especially in four genetically healthy offspring, strongly support the hypothesis that abnormal Norrin may have an adverse transplacental (environmental) effect on normal inner retinal vasculogenesis.