Spectral domain optical coherence tomography-based retinochoroidal cystine crystal score: a window into infantile nephropathic cystinosis

Abstract

PrécisCystinosis is a lysosomal storage disease leading to an accumulation of cystine crystals in several organs. We aim to comprehensively describe chorioretinal cystine crystals via spectral domain optical coherence tomography (SD-OCT) and elaborate a new biomarker for systemic disease control.Background/aimsCystinosis is a rare lysosomal storage disease leading to an accumulation of cystine crystals in several organs. This study aims to describe the deposition of retinochoroidal crystals in infantile nephropathic cystinosis and to elucidate their potential value as an objective biomarker for systemic disease control.MethodsThis cross-sectional study was carried out by the University Eye Hospital of the Ludwig-Maximilian University (Munich, Germany) in collaboration with the German Cystinosis Study Group. A complete ophthalmologic examination was performed, along with posterior segment SD-OCT (Spectralis; Heidelberg Engineering GmbH, Heidelberg, Germany). Retinochoroidal crystals were graded by employing a novel semiquantitative grading system—the retinochoroidal cystine crystal score (RCCCS). To quantify quality of vision, patients completed a specific questionnaire. A total of 85 eyes of 43 patients with cystinosis were included (mean age 22.3±8.8 years, range 6–39; male:female ratio=23:20).ResultsCystine crystals were detectable in all neuroretinal layers and the choroid, most frequently in the choriocapillaris. The RCCCS was negatively correlated with cysteamine intake (r=0.533, p=0.001) and positively with cystatin C, a stable parameter of renal function (r=0.496, p=0.016). Moreover, the value of the RCCCS affected subjective quality of vision. Genetic analysis indicated pronounced crystal deposition in patients with heterozygous mutations containing the 57-kb-deletion allele of the CTNS gene.ConclusionOcular cystinosis leads to retinochoroidal crystal accumulation in every stage of the disease. Crystal deposition may be markedly influenced by oral cysteamine therapy. Therefore, the presented SD-OCT based grading system might serve as an objective biomarker for systemic disease control.

Corneal Manifestation in Patients with Infantile Nephropathic Cystinosis

“…While oral cystine proved effective on pigmentary retinopathy, there seems to be no effect on corneal crystal density due to insufficient concentration in the corneal avascular tissue. [2,12,24] The topical cysteamine eye drops Cystaran® (0.44% cysteamine ophthalmic solution) dissolveolute corneal crystals effectively, subsequently improving symptoms like photophobia, blepharospasm and pain [19]. Even though effective, the topical application with cysteamine eye drops comes with two big disadvantages: First, it needs to be applied frequently either every waking hour or at least 6-12 times a day to be effective [25].…”

“…Because oral therapy needs to be taken frequently throughout the day, long-term compliance has become a main challenge. While oral cystine proved effective on pigmentary retinopathy, there seems to be no effect on corneal crystal density due to insufficient concentration in the corneal avascular tissue [2,12,24].…”

“…Whereas renal complications are the best known, there are many other extrarenal complications out and foremost ocular complications with patients predominantly suffering from photophobia, glared vision, starburst perception and in later stages blepharospasm. [2] Accepted Manuscript This article is protected by copyright. All rights reserved.…”

“…Whereas renal complications are the best known, there are many other extrarenal complications out and foremost ocular complications with patients predominantly suffering from photophobia, glared vision, starburst perception and in later stages blepharospasm. [2] There have been many new developments in diagnostic and therapeutic strategies over the last decades, improving life expectancy and long-term prognosis. Once thought of as childhood disease patients now commonly live well into adulthood.…”

Das Auge als Fenster zur Cystinose

“…Aufgrund der guten Perfusion von Retina und Choroidea wurde das Auftreten der Pigmentretinopathie dank der systemischen Cysteamin-Medikation ins Erwachsenenalter verschoben. Dennoch lassen sich mit der SD-OCT choroidale Cystinkristalle nachweisen, deren Dichte als Langzeitbiomarker für die Cysteamin-Therapie dienen könnte [7]. Besonderes Augenmerk sollte bei jeder augenärztlichen Untersuchung auch auf das Auftreten eines Papillenödems gelegt werden.…”