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Year : 2021  |  Volume : 1  |  Issue : 3  |  Page : 545-547

Multimodal imaging of infantile nephropathic cystinosis

1 Sri Bhagwan Mahavir Department of Vitreoretinal Services, Medical Research Foundation, Sankara Nethralaya, Chennai, Tamil Nadu, India
2 Department of Cornea and Refractive Surgery, Medical Research Foundation, Sankara Nethralaya, Chennai, Tamil Nadu, India

Date of Submission21-Jun-2020
Date of Acceptance12-Feb-2021
Date of Web Publication02-Jul-2021

Correspondence Address:
Dr. P Sen
Sri Bhagwan Mahavir Department of Vitreoretinal Services, Medical Research Foundation, Sankara Nethralaya, No 41 (Old 18) College Road, Chennai - 600 006, Tamil Nadu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijo.IJO_1977_20

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Cystinosis is a lysosomal storage disorder characterized by cystine crystal accumulation in different parts of body including the eyes. The purpose of this article was to describe different ophthalmological abnormalities in cystinosis using multimodal imaging. A 5-year-old girl with cystinosis was assessed clinically and with slit-lamp photography (SLP), anterior segment-OCT (AS-OCT), in vivo confocal microscopy (IVCM), fundus photography, swept-source optical coherence tomography (SS-OCT), and fundus autofluorescence. Based on all findings, she was diagnosed with ocular cystinosis. Corneal crystals were better visualized by IVCM than AS-OCT or SLP. Retinal crystal were well delineated by OCT.

Keywords: Corneal crystal, cystinosis, intraretinal crystal, pigmentory retinopathy

How to cite this article:
Roy KK, Sen P, Lakshmipathy M, Paul RS. Multimodal imaging of infantile nephropathic cystinosis. Indian J Ophthalmol Case Rep 2021;1:545-7

How to cite this URL:
Roy KK, Sen P, Lakshmipathy M, Paul RS. Multimodal imaging of infantile nephropathic cystinosis. Indian J Ophthalmol Case Rep [serial online] 2021 [cited 2021 Jul 26];1:545-7. Available from: https://www.ijoreports.in/text.asp?2021/1/3/545/319986

Cystinosis is a rare lysosomal storage disorder characterized by cystine crystal accumulation in different organs including the eyes. It is a rare autosomal recessive disease seen in 0.5–1 in one lakh live births in all ethnic groups throughout the world.[1],[2] Among the three clinical types, infantile nephropathic type is the most common (95%) and most severe disease, usually diagnosed within 2 years of birth. Ocular involvement includes cystine crystal accumulation at conjunctiva, cornea, iris, and retina. We describe a case of cystinosis in a child, highlighting the different aspects of the ocular involvement by using multimodal imaging.

  Case Report Top

A 5-year-old girl born from healthy, non-consanguineous parents was diagnosed with infantile nephropathic cystinosis, Arnold– Chiari malformation More Details, and benign intracranial hypertension by her pediatrician. She was referred to us for detailed ocular examination. She was asymptomatic and orthophoric. Both eyes (BE) visual acuity was 20/25 and had normal color vision and intraocular pressure. On slit-lamp photography (SLP) BE had limbus-to-limbus plenty of fine, birefringent, thin, needle-like crystal deposits at corneal stroma (more at anterior stroma) and conjunctiva [Figure 1]a and [Figure 1]b. The corneal cystine crystal density (slit-lamp score) was 0.5 in right eye (RE), 0.75 in left eye (LE; calculated by comparing with reference image described by Gahl et al.[3]). Anterior segment-optical coherence tomography (AS-OCT) by Visante Zeiss HD OCT showed a layer of hyperreflective punctuate deposit in anterior stroma in BE [Figure 1]c and [Figure 1]d with central corneal thickness (CCT) of 477 micron in RE and 483 micron in LE. The depth of crystal deposition at central cornea was 88 micron in RE and 105 micron in LE. To compensate the variation of CCT, crystal deposition depth was expressed as a percentage of CCT (RE 18.44%, LE 21.74%). In vivo confocal microscopy (IVCM) image [Figure 2], taken by HRT Rostock Cornea module in a pre-validated method,[4] revealed plenty of needle- and spindle-shaped hyperreflective bodies involving basal epithelium to posterior stroma in RE and basal epithelium to endothelium in LE. IVCM score[4] was 10 in RE and 14 in LE. Fundus photography showed bilateral disc pallor and hint of multiple subretinal small, yellowish crystal deposits at posterior pole [Figure 3]a and [Figure 3]b. Swept-source optical coherence tomography (Topcon Corporation, Tokyo, Japan) through macula revealed multiple tiny, hyperreflective, dot-like structures in different retinal layers, suggestive of intraretinal crystals with normal foveal contour and retinal layers in BE [Fig. 3c and d]. BE green autofluorescence (OPTOS) was normal. Based on all the findings, ocular cystinosis was diagnosed, and parents were explained about the need of future treatment and regular follow-ups.
Figure 1: Slit-lamp photography of the right (a) and left (b) eye of a patient with infentile nephropathic cystinosis. Anterior segment-optical coherence tomography showed a layer of hyperreflective punctate deposit at anterior stroma (arrow) in both eyes with depth of crystal deposition 88 micron in the right eye (c) and 105 micron in the left eye (d)

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Figure 2: In vivo confocal microscopy (IVCM) images (400 × 400 micron) of the cornea. Right eye IVCM (a-h) revealed crystal deposit within the basal epithelium (b), Bowman's layer (c) anterior stroma (d), middle stroma (e) and posterior stroma (f). No crystal was noted within superficial epithelium (a) and endothelium (g, h). Left eye IVCM (i-p) had crystals in all layers (j-p) except superficial epithelium (i)

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Figure 3: Color fundus photography of the right (a) and left (b) eye showed optic disc pallor and multiple subretinal small, yellowish, crystal deposits in both eyes. Swept-source optical coherence tomography of the right (c) and left (d) eye through macula revealed intraretinal crystals (circle) at different layers

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  Discussion Top

Cystinosis is caused by the mutation of CTNS gene, leading to abnormal accumulation of cystine within cellular lysosome to a crystal-forming level.[2] Infantile nephropathic cystinosis patient can develop Fanconi syndrome, delayed development,[2] intracranial hypertension, rickets, and bony deformities like Arnold–Chiari malformation type 1[5] at infancy.

Photophobia, the most common ocular symptom, is caused by crystal accumulation at cornea and conjunctiva.[6] Severity of photophobia is associated with the density of accumulation of corneal crystals. To quantify the corneal crystal density, different imaging modality and scoring systems were proposed. Slit-lamp score, a semi-quantitative photographic score, was calculated in comparison with a library of reference images with score ranging from 0–3 at 0.25 increment.[3] Once cornea is packed with crystals the “Slit-lamp score” can't differentiate the variation between crystal density, though it correlates well with self-assessed photophobia.[3],[7] SLP may be a good tool for the detection of corneal crystals in an asymptomatic patient like in the current case. AS-OCT can detect the presence and depth of crystal deposition very well but cannot analyze the appearance and distribution of crystals.[7] Though it is well tolerated and provides more information like CCT, depth of crystal deposition than SLP. IVCM provides a very high-resolution image at different levels of cornea[4] (superficial epithelium, basal epithelium, the Bowman layer, anterior stroma, middle stroma, posterior stroma, and endothelium). Each image was analyzed for crystal density (0–4) according to the percent of deposit in each image (400 × 400 micron): 0- No crystal, 1- <25%, 2- 25–50%, 3- 50–75%, 4- >75%. IVCM score was calculated by adding the density score of each layers.[7] Compared to other imaging modalities, IVCM analyzes all corneal layers at cellular level and preciously detect crystal appearance, density-associated inflammatory cell infiltration, and nerve alteration. IVCM score has direct and stronger correlation than slit-lamp score with photophobia and corneal crystal deposits.[8] Compared to AS-OCT, IVCM can measure the depth of crystal deposits more accurately but both modalities under estimate the CCT.

Cystine crystals can accumulate at surface and different layers of retina, leading to retinal pigment epithelium (RPE) degeneration, depigmented patches, and pigmentary mottling and rarely pigment deposition in inner retina.[9] Optical coherence tomography (OCT) confirms intraretinal crystals as tiny, hyperreflective, dot-like structures.[10] RPE abnormalities are particularly well delineated as stippled hypo-autofluorescence.[9] In our patient, during fundus examination, presence of multiple subretinal crystals was suspected, which was confirmed on OCT, and absence of pigmentation and hypo-autofluorescence ruled out RPE degeneration. Few patients developed papilledema and optic atrophy secondary to neurological complications; hence, optic disc examination and documentation in the form of optic disc photography are important. This child had optic atrophy secondary to benign intracranial hypertension.

  Conclusion Top

This case highlights how multimodal imaging can delineate crystals even in an asymptomatic patient with infantile nephropathic cystinosis and can help in follow-up as well as to prognosticate the visual outcome.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Nesterova G, Gahl WA. Cystinosis: The evolution of a treatable disease. Pediatr Nephrol 2013;28:51-9.  Back to cited text no. 1
Nesterova G, Gahl WA. Cystinosis. 2001 Mar 22 [Updated 2017 Dec 07]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Mirzaa G, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2021. PMID: 20301574.  Back to cited text no. 2
Gahl WA, Kuehl EM, Iwata F, Lindblad A, Kaiser- Kupfer MI. Corneal crystals in nephropathic cystinosis: Natural history and treatment with cysteamine eyedrops. Mol Genet Metab 2000;71:100-20.  Back to cited text no. 3
Jalbert I, Stapleton F, Papas E, Sweeney DF, Coroneo M. In vivo confocal microscopy of the human cornea. Br J Ophthalmol 2003;87:225-36.  Back to cited text no. 4
Rao KI, Hesselink J, Trauner DA. Chiari I malformation in nephropathic cystinosis. J Pediatr 2015;167:1126-9.  Back to cited text no. 5
Biswas S, Gaviria M, Malheiro L, Marques JP, Giordano V, Liang H. Latest clinical approaches in the ocular management of cystinosis: A review of current practice and opinion from the ophthalmology cystinosis forum. Ophthalmol Ther 2018;7:307-22.  Back to cited text no. 6
Labbe A, Niaudet P, Loirat C, Charbit M, Guest G, Baudouin C. In vivo confocal microscopy and anterior segment optical coherence tomography analysis of the cornea in nephropathic cystinosis. Ophthalmology 2009;116:870-6.  Back to cited text no. 7
Liang H, Baudouin C, Hassani RT, Brignole-Baudouin F, Labbe A. Photophobia and corneal crystal density in nephropathic cystinosis: An in vivo confocal microscopy and anterior-segment optical coherence tomography study. Invest Ophthalmol Vis Sci 2015;56:3218-25.  Back to cited text no. 8
Tsilou ET, Rubin BI, Reed G, Caruso RC, Iwata F, Balog J, et al. Nephropathic cystinosis: Posterior segment manifestations and effects of cysteamine therapy. Ophthalmology 2006;113:1002-9.  Back to cited text no. 9
Kozak I, Arevalo JF, Shoughy SS. Intraretinal crystals in nephopathic cystinosis and fanconi syndrome. JAMA Ophthalmol 2017;135:e165169.  Back to cited text no. 10


  [Figure 1], [Figure 2], [Figure 3]


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