Disambiguation of photoreceptor structure in transition zones of retinal degenerative diseases

Abstract

 

Purpose

 

Inherited retinal degenerations are commonly associated with transition zones between normal and pathologic regions. Analysis of retinal structure within these zones provides important information about disease mechanism at the cellular level. Confocal adaptive optics scanning light ophthalmoscopy (AOSLO) imaging shows numerous reflective structures in these regions which may be erroneously identified as cones. This study uses non-confocal AOSLO imaging techniques to expose the origin of the reflective structures in transition zones and provide a more definitive assessment of residual cone photoreceptor structure.

 

Methods

 

Two subjects with Stargardt’s disease (STGD), 1 subject with retinitis pigmentosa (RP), and 1 subject with Usher’s syndrome were imaged using confocal, dark-field, and split-detector AOSLO (custom-built, 790nm light). Spectral domain ocular coherence tomography (SD-OCT) images were acquired and aligned to the AOSLO.

 

Results

 

At the transition zones of the RP and Usher’s subjects, confocal AOSLO shows scattered reflective structures that are difficult to define (Fig 1A). Using dark-field and split-detector modalities reveals an increasingly visible RPE mosaic and a decreasing photoreceptor density, respectively, through the transition zone (Fig 1B, C). The loss of photoreceptors correlates with the tapering of the ellipsoid zone seen on SD-OCT in the same region (Fig 1D). Confocal AOSLO of the transition zone in the two patients with STGD showed numerous reflective structures that resemble cone photoreceptors (Fig 2A). Split-detector AOSLO of this region revealed a majority of rods, scarce cones, possible large lipid-engorged RPE cells, and a significant area of debris (Fig 2B).

 

Conclusions

 

Reflective retinal structures in transition zones of inherited retinal degenerations could be wrongly attributed to photoreceptors when assessed solely with confocal AOSLO. Reflective RPE cells or debris can be better differentiated from surviving photoreceptors when a multimodal AOSLO imaging approach is applied in patients with these degenerative diseases.

 

 

A section of the transition zone in RP viewed with A) Confocal, B) Dark-field, C) Split-detector en face AOSLO, and D) B-scan SD-OCT. Scale bar 100µm

 

 

Transition zone in STGD. A) Many reflective structures in confocal AOSLO. B) Split-detector AOSLO reveals only scarce cones (arrow), clusters of enlarged rods and debris. Scale bar 50µm

 

Keywords: 550 imaging/image analysis: clinical • 696 retinal degenerations: hereditary • 648 photoreceptors