Isolated Foveal Hypoplasia

Clinical Presentation and Imaging Findings

Abstract

Purpose 

To describe the clinical presentation and imaging findings of a patient with isolated foveal hypoplasia.

Case Report 

A 16-year-old teenager presented to our clinic with mild to moderate visual impairment since early childhood. Lack of foveal depression was noted on both clinical examination and optical coherence tomography, and absence of the foveal avascular zone was demonstrated on fluorescein angiography. His ocular examination was otherwise unremarkable.

Conclusions 

Isolated foveal hypoplasia should be considered in the differential diagnosis of early-onset bilateral visual impairment, especially when the foveal reflexes seem absent.

Foveal hypoplasia (FH) is a disorder characterized by an underdeveloped foveal pit, absence of foveal pigmentation, and/or foveal avascular zone (FAZ)¹ and persistence of inner retinal layers at the fovea.² Foveal hypoplasia has been described in conjunction with other pathologies such as oculocutaneous albinism, aniridia, albinism, microphthalmos, or achromatopsia or rarely as an isolated entity.³ We report a case of the isolated form of bilateral FH in a 16-year-old teenager. To the best of our knowledge, this is the first reported case of bilateral isolated FH in Turkey.

CASE REPORT

A 16-year-old teenager presented to the Department of Ophthalmology at the Gazi University Hospital, complaining of mild to moderate visual impairment in both eyes since early childhood. The patient was born on the 39th gestational week, with normal birth weight. His parents were not consanguineous, and he had two healthy siblings. His mother was not using any medication during her pregnancy, and there was no family history of ocular or systemic disease. The patient’s medical history was unremarkable. At presentation, his best-corrected visual acuity (VA) was 20/30 in both eyes (refractive error was −0.75 diopters in the right eye and −0.50 diopters in the left eye). His extraocular movements were full, and he was orthophoric at distance and near. There was no nystagmus and no iris transillumination defects suggestive of ocular albinism. The iris and chamber angle were normal, with no signs suggestive of aniridia (Fig. 1). Titmus testing showed impaired stereopsis. Dilated fundus examination revealed ill-defined maculofoveal areas, with absence of foveal reflexes bilaterally. The retinal vessels and capillaries were running abnormally close to both presumed macular areas, and both superior branch arterioles were crossing the horizontal meridian (Fig. 2). The vitreous, optic nerve, and retinal periphery were within normal limits in both eyes. Spectral-domain optical coherence tomography (Heidelberg Engineering, Heidelberg, Germany) images showed grade 4 foveal hypoplasia, which is characterized by the absence of foveal depression, widespread thickening of the retina, and extension of all neurosensory retinal layers in the fovea.⁴ Distinctive OCT findings of foveal hypoplasia were demonstrated in Fig. 3. Fundus autofluorescence imaging did not show the typical foveal darkening caused by light absorption by macular pigment (Fig. 4). The FAZ was absent in the fluorescein angiogram (Fig. 5). Color vision (Ishihara color plates) and full-field electroretinogram were normal in both eyes. Genetic testing was suggested but not obtained.

FIGURE 1: Anterior segment examination showed a normal iris without transillumination defects and normal angle structures (A, right eye; B, left eye).

FIGURE 2: Fundus examination showed absent foveal reflexes. The retinal vessels and capillaries, running abnormally close to both presumed macular areas, and the superior branch arterioles crossing the horizontal meridian (A, right eye; B, left eye).

FIGURE 3: Spectral-domain OCT showing foveal hypoplasia characterized by the absence of extrusion of plexiform layers, absence of foveal pit, absence of outer segment lengthening, and absence of outer nuclear layer widening (horizontal scans of the [A] right eye and the [B] left eye).

FIGURE 4: Fundus autofluoresence showing the absence of foveal reflexes (A, right eye; B, left eye).

FIGURE 5: Fluorescein angiography demonstrating the absence of the foveal avascular zone (FAZ) (A, right eye; B, left eye).

DISCUSSION

Foveal hypoplasia may be found in patients with aniridia, albinism, and nystagmus but rarely appears in isolation. We report on a 16-year-old teenager with isolated FH, who presented to our clinic with bilateral mild to moderate visual impairment since early childhood. His fundus examination demonstrated absence of normal foveal structure. His spectral-domain optical coherence tomography and fluorescein angiogram showed absence of the foveal depression and FAZ in both eyes, without concomitant ocular or systemic pathology.

Normal foveal development occurs in several distinctive stages.⁵ First, cells of the inner retina migrate toward the periphery, then cone photoreceptors migrate toward the preliminary foveal area, followed by cone photoreceptors specializing as foveal cone photoreceptors. Starting at fetal week 25, outward displacements of the inner retinal layers begin to form the foveal pit. Postnatally, cone elongation and packing are usually completed, and the pit shape changes from narrow and deep to wide and shallow. Cone photoreceptors migrate toward the preliminary foveal area, thus, outer nuclear layer is expanding and OCT shows specialization of cone photoreceptors as outer segment lengthening.^4,6

The foveal region remains avascular throughout the fetal development, and FH is considered the result of failure of the FAZ to normally form.^7–9 If blood vessels invade the future foveal pit region, a shallow and incomplete pit formation occur.^7,10

 The relationship between formation of foveal depression and VA is poorly understood. Thomas et al.⁴ suggested that OCT may be an important ancillary diagnostic tool used as a prognostic indicator in FH. The authors identified four grades of FH, from grade 1, showing only a shallow foveal pit, to grade 4 with features that include complete absence of the foveal pit. They found a significant difference in VA associated with each grade (p < 0.0001). Others described more rare forms of FH, in which there was no clear structure-function correlation. Mota et al.¹¹ did report that the role of foveal depression was not confirmed as a VA prognostic factor. However, two cases reported in this article were grade 1 FH, using Thomas et al. grading system. Marmor et al.¹² reported on four patients with a range of VAs from 20/20 to 20/50—none of them having a visible foveal pit. Issa et al.¹³ suggested that an intact foveal anatomy is related to macular pigment density and correlated with VA. However, foveal cone specialization could be preserved anatomically and functionally despite the absence of a foveal pit. This explains why some patients, such as the patient presented herein, may have a relatively good VA despite the absence of a normal foveal depression.¹² In addition, some authors suggested that photoreceptor damage, IS/OS disruption, and outer nerve fiber layer thinning may be related to achromatopsia.^1,4,14 However, in our patient, color vision was normal, suggesting that his photoreceptor layer is probably preserved.

Isolated FH is most commonly sporadic, but association with PAX6 missense mutation was identified.¹⁵ In some isolated cases, PAX6 has been screened but no mutations were found.¹⁶ Homozygous mutations in SLC38A8 have been found to be inherited with FH among families of Jewish Indian ancestry. Nystagmus and reduced vision but no anterior segment abnormalities were present.¹⁷ Although the term “aniridia” suggests absence of the iris, the actual amount of iris remnant varies among individuals. The literature reports that the diagnosis of aniridia can be easily missed in cases of PAX6 missense mutations because PAX6 mutations can cause various phenotypes that can range from a readily visible almost complete absence of the iris to small slitlike defects in the anterior layer of the iris.¹⁸ We performed meticulous anterior segment examination and did not find any iris transillumination defects. Genetic testing was offered to our patient; however, unfortunately, it was not obtained.

In conclusion, we present a rare case of isolated FH in a visually impaired teenager. This rare case report of isolated FH differs from previous reports in that the patient was diagnosed with an advanced disease (grade 4 FH by Thomas et al. grading system), and still his VA was only mildly reduced, and there was no nystagmus associated. Such an advanced structural disease with only a relatively mild functional impairment is rare and was only scarcely reported before. Isolated FH should be considered in the differential diagnosis of bilateral visual impairment, especially in cases where the foveal reflex seems absent.

ACKNOWLEDGMENTS

The authors have no proprietary or commercial interest in any material or method mentioned.

Received November 6, 2013; accepted December 16, 2013.