Adaptive optics microperimetry and OCT images show preserved function and recovery of cone visibility in macular telangiectasia type 2 retinal lesions

Abstract

Purpose: To evaluate visual function and disease progression in the retinal structural abnormalities of three patients from two unrelated families with macular telangiectasia (MacTel) type 2.

Methods: Adaptive optics scanning laser ophthalmoscopy (AOSLO) and AOSLO microperimetry (AOMP) were used to evaluate the structure and function of macular cones in three eyes with MacTel type 2. Cone spacing was estimated using histogram analysis of intercone distances, and registered spectral-domain optical coherence tomography (SD-OCT) scans were used to evaluate retinal anatomy. AOMP was used to assess visual sensitivity in and around areas of apparent cone loss.

Results: Although overall lesion surface area increased, some initially affected regions subsequently showed clear, contiguous, and normally spaced cone mosaics with recovered photoreceptor inner/outer segment (IS/OS) reflectivity (two of two eyes). The AOMP test sites fell within three categories: normal-appearing cones (N), dimly reflecting cones (D), and RPE cell mosaics (R). At N sites, AOMP threshold values (arbitrary units [au]) increased with increasing eccentricity (slope = 0.054 au/degree, r(2) = 0.77). The N thresholds ranged from 0.04 to 0.27 au, D thresholds from 0.04 to 0.33 au, and R thresholds from 0.14 to 1.00 au. There was measurable visual sensitivity everywhere except areas without intact external limiting membrane (ELM) and with diffuse scattering in the IS/OS and posterior tips of the outer segments (PTOS) regions on OCT.

Conclusions: Visual sensitivity and recovery of cone visibility in areas of apparent focal cone loss suggests that MacTel type 2 lesions with a preserved ELM may contain functioning cones with abnormal scattering and/or waveguiding characteristics. (ClinicalTrials.gov number, NCT00254605.).

Keywords: AOMP; AOSLO; MacTel type 2; cone photoreceptors.

Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

Figures

Figure 1

Clinical findings in patients with MacTel type 2. Color fundus photos (row A) reveal subtle MacTel type 2 features, such as loss of retinal transparency and telangiectatic vessels temporal to the fovea. These are more clearly seen with evidence of hyperfluorescence on FA images (row B) and fundus autofluorescence images (row C).

Figure 2

Relative location and size of MacTel type 2 lesions studied with AOSLO montages superimposed on clinical images. In F2P2, the patient with earliest disease, telangiectatic vessels temporal to the fovea and inner retinal microcysts are the only abnormal findings.

Figure 3

Disease progression in two MacTel type 2 patients. Baseline lesion boundaries are outlined in blue on AOSLO and correlated with OCT B-scans via yellow, vertical dashed lines. Tan lines indicate location of OCT B scans shown below each AOSLO montage. Visual acuity, PRL (white clusters), and IS/OS breaks on OCT (red arrowheads) are shown. (A, B) AOSLO (top row): There is nasal expansion from 2011 to 2013. Within the blue rectangle, there are newly resolvable, hyperreflective cones temporally that are not seen in (A). OCT (bottom row): Selected scan shows anatomy at all three AOSLO-defined categories (N, D, R). The reflectivity of the IS/OS line within the lesion is relatively dim compared with outside the lesion. In (A), the dashed vertical lines do not correspond exactly with IS/OS breaks. In (B), the same dashed lines show that temporally, a small, previously dark IS/OS segment in 2011 is hyperreflective in 2013 (yellow arrow). VA, PRL: The decline in VA coincides with a shift in PRL. (C, D) AOSLO: There is nasal extension from 2010 to 2014. Within the blue rectangle, there are apparent cones in a formerly dim region temporal to the vertical retinal vascular landmark. OCT: The IS/OS defect has increased and extended nasally. A small, previously dark IS/OS segment in 2010 appears hyperreflective in 2014 (yellow arrow). Note: The difference in foveal contours between (C) and (D) is likely due to loss of outer retinal layers, as demonstrated in Figure 4B, B-scans a through e. VA, PRL: VA stable, PRL center unchanged during the course of the study.

Figure 4

Cone structure and function in MacTel type 2 study eyes, shown via AOSLO montages, OCT scan lines, OCT B-scans, AOMP test site locations (colored squares, actual test stimulus size), and average AOMP threshold values (reported in au). Extent of threshold elevation compared with expected indicated by color. White stars mark foveas. Scale bar: 1°. B-scans were scaled and registered with vasculature before miniaturization (33% original). Scans show retinal anatomy at AOMP test sites (blue arrows). (A) AOSLO: MacTel type 2 lesion with RPE cells (R sites) and dim areas (D sites). (a–f) OCT: IS/OS breaks appear to have overlying preserved ELM bands (white arrows); RPE areas correspond to definitive IS/OS breaks on B-scans. Dim areas correspond with a range of IS/OS findings: test site 9 corresponds to an unambiguous break; 2, 4, and 8 to a present but relatively weakly reflecting IS/OS. AOMP: Measureable threshold values (au ±1 SD) at RPE sites are less abnormal than value at D site 2. (B) AOSLO: Visible RPE mosaics and dimly reflecting regions. OCT: Concurrent IS/OS and ELM disruptions (white arrow) correspond to AOMP R sites (4, 5), whereas D site 3 colocalizes with a present but weakly reflective IS/OS. AOMP: R site thresholds exceed thresholds in normal-appearing and dim areas. (C) AOSLO: Shadows of inner retinal abnormalities (pink rectangle). OCT: No disruption of the IS/OS junction band or ELM band. AOMP: Thresholds increased with eccentricity, with site 3 elevated more than site 2 or 4.

Figure 5

Adaptive optics MP thresholds from all three study eyes are shown. Thresholds at normal (N, black) locations increase with eccentricity and serve as comparison for thresholds at dim (D, blue) and RPE (R, red) sites.