Structural grading of foveal hypoplasia using spectral-domain optical coherence tomography a predictor of visual acuity?

Abstract

Purpose: To characterize and grade the spectrum of foveal hypoplasia based on different stages of arrested development of the fovea. Grading was performed using morphologic findings obtained by ultra high-resolution spectral-domain optical coherence tomography. Best-corrected visual acuity (BCVA) was calculated for different grades.

Design: Observational case series.

Participants and controls: Sixty-nine patients with foveal hypoplasia (albinism, n = 34; PAX6 mutations, n = 10; isolated cases, n = 14; achromatopsia, n = 11) and 65 control subjects were examined.

Methods: A 7×7-mm retinal area was sampled using a 3-dimensional scanning protocol (743×75, A scans×B scans) with ultra high-resolution spectral-domain optical coherence tomography (SOCT Copernicus HR; 3-μm axial resolution). Gross morphologic abnormalities were documented. B-scans at the fovea were segmented using a longitudinal reflectivity profile. Logarithm of the minimum angle of resolution BCVA was obtained.

Main outcome measures: Grading was based on presence or absence of foveal pit and widening of the outer nuclear layer (ONL) and outer segment (OS) at the fovea. Quantitative measurements were obtained for comparing atypical foveal hypoplasia in achromatopsia. Best-corrected visual acuity was compared with the grade of foveal hypoplasia.

Results: Four grades of foveal hypoplasia were distinguished: grade 1, shallow foveal pit, presence of ONL widening, presence of OS lengthening; grade 2, grade 1 but absence of foveal pit; grade 3, grade 2 but absence of OS lengthening; grade 4, grade 3 but absence of ONL widening. There was significant difference in visual acuity (VA) associated with each grade (P<0.0001). Grade 1 was associated with the best VA (median VA, 0.2), whereas grades 2, 3, and 4 were associated with progressively poorer VA with a median VA of 0.44, 0.60, and 0.78, respectively. The atypical features seen with foveal hypoplasia associated with achromatopsia were characterized by decreased retinal and ONL thickness and deeper foveal depth.

Conclusions: A structural grading system for foveal hypoplasia was developed based on the stage at which foveal development was arrested, which helps to provide a prognostic indicator for VA and is applicable in a range of disorders associated with foveal hypoplasia. Atypical foveal hypoplasia in achromatopsia shows different characteristics.

Financial disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Figure 1

Chart showing the 3 developmental processes involved information of a structural and functional fovea. In grade 1 foveal hypoplasia, all processes occur to a certain extent. However, in grade 4 foveal hypoplasia, none of these processes occur; thus, the retina resembles that of the parafovea. In grade 2 and 3 foveal hypoplasia, there is outer nuclear layer widening, but no foveal pit. The difference between grade 2 and 3 foveal hypoplasia is occurrence of cone photoreceptor specialization. Identifying these specific features on optical coherence tomography (OCT) enables us to understand whether the respective developmental process has occurred.

Figure 2

A, Optical coherence tomography scan showing a normal fovea with description of the normal foveal elements. Optical coherence tomography scans showing the spectrum of foveal hypoplasia seen in various conditions, including: (B, C) albinism, (D, E) associated with PAX6 mutations, (F, G) isolated cases, and (H, I) an atypical form of foveal hypoplasia seen in achromatopsia. A hyporeflective zone (cavitation) is also seen (I) that is a sign of cone photoreceptor degeneration. Both foveal hypoplasia and fovea plana were seen in all disorders except the achromatopsia, which results in an atypical form of foveal hypoplasia with a shallower pit, incursion of the plexiform layers, and disruption of the inner segment (IS)/outer segment (OS) junction. INL = inner nuclear layer; NFL = nerve fiber layer; ONL = outer nuclear layer.

Figure 3

A, Illustration showing the unique features of a normal fovea detectable on optical coherence tomography. B, Illustration of typical and atypical grades of foveal hypoplasia. All grades of foveal hypoplasia had incursion of inner retinal layers. Atypical foveal hypoplasia also had incursion of the inner retinal layers. Grade 1 foveal hypoplasia is associated with a shallow foveal pit, outer nuclear layer (ONL) widening, and outer segment (OS) lengthening relative to the parafoveal ONL and OS length, respectively. In Grade 2 foveal hypoplasia, all features of grade 1 are present except the presence of a foveal pit. Grade 3 foveal hypoplasia consists of all features of grade 2 foveal hypoplasia except the widening of the cone outer segment. Grade 4 foveal hypoplasia represents all the features seen in grade 3 except there is no widening of the ONL at the fovea. Finally, an atypical form of foveal hypoplasia also is described in which there is a shallower pit with disruption of the inner segment/outer segment (IS/OS) junction, possibly a sign of photoreceptor degeneration. The atypical form of foveal hypoplasia is seen with achromatopsia, whereas grades 1 through 4 are seen with albinism, PAX-6 mutations, and isolated cases. ELM = external limiting membrane; GCL = ganglion cell layer; INL = inner nuclear layer; IPL = inner plexiform layer; OPL = outer plexiform layer; RNFL = retinal nerve fibre layer; RPE = retinal pigment epithelium.

Figure 4

Algorithm used for grading foveal hypoplasia based on optical coherence tomography findings. The hallmark of foveal hypoplasia is incursion of the inner retinal layers. Based on disruption of the inner segment/outer segment (IS/OS) junction of the photoreceptor, the foveal hypoplasia is classified into either typical or atypical foveal hypoplasia. The grade of foveal hypoplasia can be determined based on whether the following features are present or absent: outer segment (OS) lengthening, foveal pit, and outer nuclear layer (ONL) widening.

Figure 5

A, Bar graph showing the number of patients within each grade of foveal hypoplasia; the proportion of different disorders within each grade are shown with different shades. B, Box plots of visual acuity (VA) for each grade of foveal hypoplasia. The results of multiple comparisons of how grade of foveal hypoplasia affects VA are shown with the respective P values and median difference (d) in VA measured in logarithm of the minimum angle of resolution (logMAR) units. C, Box plot showing that similarly, there was a significant difference in visual acuity between the typical forms of foveal hypoplasia and atypical foveal hypoplasia. The other features that were significantly different between the controls and typical and atypical forms of foveal hypoplasia were: (D) retinal thickness at the fovea, (E) outer nuclear layer thickness, and (F) foveal depth. For all box plots, the whiskers represents the maximum and minimum range of observations, whereas the box represents the interquartile range and the line dividing the box represents the median. All multiple comparisons are shown with the box plots with the significance values and median differences (d), units for which are logMAR (for B and C) or micrometers (for D, E, and F).