From the Department of Ophthalmology, Hopital Intercommunal de Creteil, University Paris XII, France.
The authors have no financial or proprietary interest in the materials presented herein.
Address correspondence to Giuseppe Querques, MD, Department of Ophthalmology, University of Paris XII, Centre Hospitalier Intercommunal de Creteil, 40 Avenue de Verdun, 94000 Creteil, France.
Bietti’s crystalline dystrophy is an autosomal recessive retinal degeneration characterized by innumerable glistening intraretinal dots scattered over the fundus, first described by Bietti in 1937.1,2 The exact location of retinal crystals has not yet been conclusively determined, either by clinical or histological assessment.3–5
Spectral domain optical coherence tomography (Spectralis SD-OCT, Heidelberg Engineering, Heidelberg, Germany) is a high-speed OCT system (up to 40 000 axial scans per second) using spectral/Fourier domain detection, with an axial image resolution of 5 μm. Moreover, Spectralis SD-OCT, by using confocal scanning laser ophthalmoscopy (cSLO) technology to track the eye and guide OCT to the selected location, gives a real-time reference for locating the SD-OCT scan. Hence, in-vivo visualization of intraretinal structures is possible.
In this study, we tried to assess in-vivo, the location of retinal crystals in a patient with Bietti’s crystalline dystrophy using Spectralis SD-OCT.
A 39-year-old woman affected with Bietti’s crystalline dystrophy was referred to our department. The patient signed a comprehensive consent form according to good clinical practice guidelines, before proceeding with the any examinations. Her visual acuity was 20/64 in both her right eye (RE) and left eye (LE). Slit-lamp biomicroscopy revealed fine crystals in the limbal cornea bilaterally. Fundus examination showed bilateral macular pigment mottling and depigmentation, and numerous tiny refractile yellow dots scattered throughout the posterior pole and the mid-periphery, associated with diffuse choroidal and retinal pigment epithelium (RPE) atrophy and pigment accumulation (Fig. 1). Fundus autofluorescence (FAF) revealed widespread hypo-autofluorescence corresponding to diffuse RPE atrophy, and multiple hyper-autofluorescent areas in correspondence of residual RPE (Fig. 1). No hyper-autofluorescence was detected in correspondence of the retinal crystals. Both fluorescein angiography (FA) (Fig. 1) and indocyanine green angiography (ICGA) showed diffuse advanced choroidal atrophy characterized by a marked loss of the RPE and choriocapillaris, and multiple hyper-fluorescent areas in correspondence of residual RPE. Spectralis SD-OCT frames showed the retinal crystals as tiny hyper-reflective lesions localized in all retinal layers from the RPE to the retinal nerve fibre layer, and in some cases, associated with microcystic changes, mostly when localized within the inner and outer nuclear layers (Fig. 2).
Figure 1. Color Fundus Photographs (A and B) Showing Bilateral Macular Pigment Mottling and Depigmentation, and Numerous Tiny Refractile Yellow Dots Scattered Throughout the Posterior Pole and the Mid-Periphery, Associated with Diffuse Choroidal and Retinal Pigment Epithelium (RPE) Atrophy and Pigment Accumulation. Fundus Autofluorescence Frames Revealing Widespread Hypo-Autofluorescence Corresponding to Diffuse RPE Atrophy, and Multiple Hyper-Autofluorescent Speckles in Correspondence of Residual RPE Areas (C and D). No Hyper-Autofluorescence Can Be Detected in Correspondence of the Retinal Crystals (C and D). Fluorescein Angiography (E and F) Showing Diffuse Advanced Choroidal Atrophy Characterized by a Marked Loss of the RPE and Choriocapillaris, and Multiple Hyper-Fluorescent Areas in Correspondence of Residual RPE.
Figure 2. Infrared and Spectralis Spectral Domain Optical Coherence Tomography (SD-OCT) Frames Showing the Exact Correspondence Between the Retinal Crystals and the Tiny Hyper-Reflective SD-OCT Lesions (A–D). The Retinal Crystals Appear Localized in All Retinal Layers, from the RPE to the Retinal Nerve Fibre Layer on the SD-OCT Frames. These Hyper-Reflective SD-OCT Lesions Appear Associated with Microcystic Changes, Mostly when Localized Within the Inner and Outer Nuclear Layers.
Patients with Bietti’s crystalline dystrophy present with visual symptoms (decrease in visual acuity, often accompanied by nictalopia) from the third decade onward. In these patients, crystalloid lysosomal inclusions resembling cholesterol esters have been detected in peripheral lymphocytes, skin, conjunctival, corneal, and choroidal fibroblasts. The differential diagnoses of Bietti’s crystalline dystrophy include oxalosis, cystinosis, canthaxantine use, tamoxifen use, talc emboli, Sjogren Larsson syndrome, idiopathic juxtafoveal retinal telangiectasia and gyrate atrophy. A detailed medical history, thorough systemic and ocular examination, is usually sufficient to exclude these conditions. Our patient did not show any features of these diseases.
In a patient with Bietti’s crystalline dystrophy, Meyer et al.,3 using first generation time domain OCT, showed that the entire neuroretina (from the nerve fibre layer to the photoreceptors) appeared as a homogenous hyper-reflective band, and concluded that separate layers of the retinal structure cannot be distinguished in Bietti’s crystalline dystrophy. In a recently published study, Ayata et al.,4 using time domain cSLO OCT, showed diffuse hyper-reflective granules within the entire neuroretina, similar to the ones reported by Meyer et al.,3 and demonstrated that some of these granules corresponded to crystalline dots.
In our patient, using Spectralis SD-OCT, we were able to show the exact correspondence between the retinal crystals, as visualized by infrared frame, and the tiny hyper-reflective SD-OCT lesions, which appeared localized in all retinal layers, from the RPE to the retinal nerve fibre layer. These hyper-reflective SD-OCT lesions appeared associated with microcystic changes, mostly when localized within the inner and outer nuclear layers.
Our OCT findings (hyper-reflective lesions localized in all retinal layers) are different from the ones reported in tamoxifen6 and canthaxanthine7 retinopathies (inner retinal hyper-reflective lesions, from the internal limiting membrane to the outer plexiform layer). These data suggest a different intraretinal localization of the crystalloid inclusions between Bietti’s crystalline dystrophy and some drug-induced crystalline retinopaties.
- Bietti GB: Su alcune forme atipiche o rare di degenerazione retinica (degenerazione tappeto retiniche e quadri morbosi similari). Boll Oculist. 1937;16:1159–1244.
- Bietti GB: Uber familiares Vorkommen von “retinitis punctata albescens” (verbunden mit “dystrophia marginalis cristallinza cornea”), Glitzern des Glaskorpers und anderen degenerativen Augenverunderungen. Klin Monatsbl Augenheilkd. 1937;99:737–757.
- Meyer CH, Rodrigues EB, Mennel S, Schmidt JC. Optical coherence tomography in a case of Bietti’s crystalline dystrophy. Acta Ophthalmol Scand. 2004;82:609–612. doi:10.1111/j.1600-0420.2004.00272.x [CrossRef]
- Ayata A, Tatlipinar S, Unal M, Ersanli D, Bilge AH. Autofluorescence and OCT features of Bietti’s crystalline dystrophy. Br J Ophthalmol. 2008;92:718–720. doi:10.1136/bjo.2008.138958 [CrossRef]
- Kaiser-Kupfer MI, Chan CC, Markello TC, et al. Clinical biochemical and pathologic correlation in Bietti’s crystalline dystrophy. Am J Ophthalmol. 1994:118: 569–582.
- Bourla DH, Sarraf D, Schwartz SD. Peripheral retinopathy and maculopathy in high-dose tamoxifen therapy. Am J Ophthalmol. 2007;144:126–128. doi:10.1016/j.ajo.2007.03.023 [CrossRef]
- Chan A, Ko TH, Duker JS. Ultrahigh-resolution optical coherence tomography of canthaxanthine retinal crystals. Ophthalmic Surg Lasers Imaging. 2006;37:138–139.