Small Case Series
Oct 2012

Spectral-Domain Optical Coherence Tomographic Characteristics of Autosomal Recessive Isolated Foveal Hypoplasia

Author Affiliations

Author Affiliations: Department of Ophthalmology, Maimonides Medical Center, Brooklyn (Drs Saffra and Agarwal) and The New York Eye and Ear Infirmary, New York (Mr Masini and Dr Bertolucci); and Molecular Diagnostic Laboratory, Casey Eye Institute, Oregon Health and Science University, Portland (Dr Chiang).

Arch Ophthalmol. 2012;130(10):1324-1327. doi:10.1001/archophthalmol.2012.1807

Foveal hypoplasia, also referred to as foveal planum, is a congential condition that can be associated with other ocular abnormalities such as aniridia, albinism, microphthalmos, and achromatopsia.1 Isolated foveal hypoplasia (IFH) is an even rarer disorder, with similar clinical findings in the fovea. The characteristic findings of patients with IFH are nystagmus, poor visual acuity, absent or abnormal maculofoveal reflexes on ophthalmoscopy, and variable and incomplete filtering of the choroidal fluorescence in the macular area on fluorescein angiography. No single hereditary pattern has been established for patients with IFH. Reported cases include patients with autosomal dominant and autosomal recessive inheritance patterns as well as sporadic cases.15 Only recently has a grading system for the spectral-domain (SD) optical coherence tomographic (OCT) findings of foveal hypoplasia been reported.2

Herein, we report the first case series to describe the foveal characteristics on SD-OCT imaging of 5 affected individuals in a single family affected with autosomal recessive IFH with an absent PAX6 mutation.

Report of Cases

The affected individuals in our cohort are all siblings with healthy parents (no history of consanguinity), with 5 of 12 progeny having IFH (Figure 1). Of the 12 siblings, 7 were male and 5 were female. Of the 5 with IFH, 4 were male and 1 was female. All 5 affected members manifested decreased visual acuity (mean, 0.82 logMAR; visual acuities of affected siblings were 20/100 OU in sibling 1, 20/70 OU in sibling 4, 20/70 ODand 20/100 OS in sibling 6, 20/80 OD and 20/100 OS in sibling 8, and counting fingers at 3 ft OU in sibling 10), pendular nystagmus with variable null points in each affected individual, low to moderate hyperopia (mean hyperopia, 3.3 diopters), dark hair color, normal anterior segment on slitlamp examination, and absent iris transillumination defects. Dilated retinal examinations of each of the affected individuals revealed normal optic discs, absent foveal depression, absent foveal pit, and a normal retinal periphery (Figure 2). Multifocal electroretinographic results were normal in both affected and unaffected family members. Imaging with SD-OCT (Cirrus high-definition OCT; Carl Zeiss Meditec) in all 5 affected siblings demonstrated absent foveal depression, absence of extrusion of plexiform layers, absence of outer segment lengthening, and absence of outer nuclear layer widening, all features corresponding to grade 4 foveal hypoplasia as described by Thomas et al2 (Figure 3, Figure 4,

, and
). Imaging with SD-OCT in the unaffected siblings demonstrated normal foveal anatomy. Mutation analysis for PAX6 was performed on saliva samples of both affected and unaffected siblings (Oragene DNA kit; DNA Genotek Inc). No PAX6 mutation was found.

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Figure 1. Pedigree of the family with isolated foveal hypoplasia. Both parents were healthy. Affected siblings with nystagmus, poor visual acuity, and isolated foveal hypoplasia (siblings 1, 4, 6, 8, and 10) are shaded in blue. Squares indicate males; circles, females.

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Figure 2. Fundus photographs of 3 of 5 affected siblings with isolated foveal hypoplasia show normal optic discs with a poorly defined foveal region and loss of foveal pit. The central circular white reflex is an artifact. All 5 siblings had a normal anterior segment and normal multifocal electroretinographic findings. A, Fundus of the right eye in sibling 1, a 35-year-old man with visual acuity of 20/100 OU. B, Fundus of the right eye in sibling 4, a 30-year-old man with visual acuity of 20/70 OU. C, Fundus of the right eye in sibling 6, a 26-year-old woman with visual acuity of 20/70 OD and 20/100 OS.

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Figure 3. Spectral-domain optical coherence tomographic scan showing the normal foveal anatomy and structural details. ELM indicates external limiting membrane; GCL, ganglion cell layer; ILM, internal limiting membrane; INL, inner nuclear layer; IPL, inner plexiform layer; IS/OS, inner photoreceptor segment/outer photoreceptor segment junction; NFL, nerve fiber layer; ONL, outer nuclear layer; OPL, outer plexiform layer; OPR, outer segment photoreceptor/retinal pigment epithelium complex; and RPE, retinal pigment epithelium. The dashed lines highlight the normal foveal pit (*), extrusion of plexiform layers (†), ONL widening (‡), and outer segment lengthening (§). Foveal grading is described as the following: grade 1, shallow foveal pit, presence of ONL widening, and presence of outer segment lengthening; grade 2, grade 1 but absence of foveal pit; grade 3, grade 2 but absence of outer segment lengthening; and grade 4, grade 3 but absence of ONL widening.3

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Figure 4. Grade 4 foveal hypoplasia by spectral-domain optical coherence tomographic imaging in the right eyes of 3 of 5 affected siblings, including sibling 1 (A), sibling 4 (B), and sibling 6 (C). Grade 4 foveal hypoplasia is 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. Scanning laser ophthalmoscopic imaging also demonstrates the lack of a well-defined foveal area. I indicates inferior; N, nasal; S, superior; and T, temporal.


Isolated foveal hypoplasia is an unusual condition whose phenotypic findings may reflect several genotypes. Hence, variable inheritance patterns have been reported in the literature. The arrival of SD-OCT now allows us to potentially differentiate some of these subtypes, something that was not available to previous investigators.1,3,4 The ability to test for the presence of the PAX6 mutation is another potential way to differentiate between subgroups that was not available to earlier investigators.

Previous studies2,5 have reported SD-OCT findings in patients with IFH. Thomas et al2 described 14 patients with nonfamilial IFH, absent PAX6 mutation, a mean best-corrected visual acuity of 0.2 logMAR, and grade 1 foveal hypoplasia on SD-OCT imaging. Charbel Issa et al5 described 2 patients with foveal hypoplasia in their series, one associated with posterior embryotoxon and the second with IFH. Applying the recently published SD-OCT grading system2 to the images by Charbel Issa et al5 demonstrates foveal hypoplasia grades 3 and 4, respectively (correlating to their reported best-corrected visual acuities of 0.2 and 0.4 logMAR, respectively). The PAX6 mutation status was not reported for the patients in their series.5

In our case series, we describe 5 affected individuals with familial IFH with an autosomal recessive inheritance pattern and absent PAX6 mutation. Our patients have a mean best-corrected visual acuity of 0.82 logMAR and grade 4 foveal hypoplasia on SD-OCT imaging. Our cohort's poorer best-corrected visual acuity and more severe grade of foveal hypoplasia demonstrated on SD-OCT imaging support the correlation of structure and function as well as the grading system described by Thomas et al.2

To our knowledge, this is the first case series to describe the foveal characteristics on SD-OCT imaging in a family with autosomal recessive IFH and absent PAX6 mutation. The uniqueness of the SD-OCT findings and the inheritance pattern suggest that our cohort likely represents a different subtype of IFH. The use of SD-OCT in assessing the foveal characteristics and correlating the findings with visual function in patients with IFH may lead us to better understand and isolate different subsets of this rare condition for additional study.

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Article Information

Correspondence: Dr Saffra, Department of Ophthalmology, Maimonides Medical Center, 902 49th St, Brooklyn, NY 11219 (

Financial Disclosure: None reported.

Online-Only Material: The videos are available here.

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