Elsevier

Ophthalmology

Volume 116, Issue 5, May 2009, Pages 870-876
Ophthalmology

Original article
In Vivo Confocal Microscopy and Anterior Segment Optical Coherence Tomography Analysis of the Cornea in Nephropathic Cystinosis

https://doi.org/10.1016/j.ophtha.2008.11.021Get rights and content

Objective

To analyze the corneas of patients with nephropathic cystinosis using in vivo confocal microscopy (IVCM) and anterior segment optical coherence tomography (AS-OCT).

Design

Prospective case series.

Participants

Sixteen eyes of 8 patients with nephropathic cystinosis aged 8 to 21 years.

Methods

The ophthalmologic evaluation included best-corrected visual acuity, evaluation of photophobia (0–4), slit-lamp biomicroscopy analysis, intraocular pressure measurement, evaluation of crystal density using a slit-lamp–based scoring of the cornea, as well as AS-OCT and IVCM analysis.

Main Outcome Measures

The depth of crystal deposition (DCD) in the central cornea and the central cornea thickness (CCT) were assessed using AS-OCT and IVCM. The IVCM images were evaluated for crystal density in each corneal layer and an IVCM score was calculated for each eye.

Results

All eyes had corneal crystal deposits, with a mean slit-lamp photography score of 2.90±0.13 (range, 2.75–3.00). Using AS-OCT, corneal crystals were observed in all eyes. These crystals appeared as hyperreflective punctuate deposits, predominantly observed within the anterior stroma. Measured with AS-OCT, the mean depth of DCD in the central cornea was 291.40±81.42 μm (range, 200–531 μm); the mean CCT was 543.47±29.62 μm. Using IVCM, the crystals appeared as spindle, needle-shaped, and fusiform hyperreflective bodies measuring from 1 to 175 μm in length and 1 to 30 μm in thickness. Except for the endothelium, randomly oriented crystals were observed in all corneal layers, with the greatest density observed within the anterior stroma. Measured with IVCM, the mean DCD was 426.07±88.19 μm (range, 284–531 μm); the mean CCT was 531.87±34.77 μm. There was no significant difference between the CCT measurements obtained with IVCM and with AS-OCT (mean difference, 11.31 μm; P = 0.07). Nevertheless, the DCD was significantly higher with IVCM than with AS-OCT (mean difference, 126.25 μm; P<0.0001).

Conclusions

In patients with nephropathic cystinosis, IVCM could precisely quantify the density of crystals within the central cornea. Anterior segment OCT and IVCM should be used in further studies evaluating crystal deposition in patients with nephropathic cystinosis.

Financial Disclosure(s)

The authors have no proprietary or commercial interest in any materials discussed in this article.

Section snippets

Patients and Methods

Eight patients with infantile nephropathic cystinosis were included in this study. There were 6 females and 2 males with a mean age of 12.5±4.6 years (range, 8–21). Nephropathic cystinosis was diagnosed based on a typical clinical presentation and a leukocyte cystine concentration >3 nmol half-cystine per milligram of protein. All patients took systemic cysteamine (Cystagon, Orphan Europe, Paris, France) and cysteamine eye drops (cysteamine hydrochloride 0.1%, Pharmacie Centrale des Hôpitaux de

Results

The 16 eyes of the 8 patients were evaluated in this study. All patients had normal or a near-normal visual acuity, with a mean best-corrected visual acuity of 0.08±0.13 logarithm of the minimum angle of resolution (range, 0.3 to −0.06). Mean photophobia was 2.47±0.92 (range, 1–4). Mean intraocular pressure was 11.53±2.33. All eyes had corneal crystal deposits, with a mean slit-lamp photography score of 2.90±0.13 (range, 2.75–3.00; Fig 2). Clinical data are summarized in Table 1.

Using AS-OCT,

Discussion

The IVCM images provided a precise, qualitative, and quantitative assessment of crystal deposition within the cornea of patients with nephropathic cystinosis. To our knowledge, the description of these deposits using IVCM has already been presented, but only in 4 individual case reports and with controversial findings concerning the presence of crystals within the epithelium, the corneal layer with the highest crystal density, and the orientation of these crystals.13, 14, 15, 16 In the study

References (27)

  • E.T. Tsilou et al.

    Age-related prevalence of anterior segment complications in patients with infantile nephropathic cystinosis

    Cornea

    (2002)
  • M.I. Kaiser-Kupfer et al.

    Long-term ocular manifestations in nephropathic cystinosis

    Arch Ophthalmol

    (1986)
  • J.L. Dufier et al.

    Ocular changes in long-term evolution of infantile cystinosis

    Ophthalmic Paediatr Genet

    (1987)
  • Cited by (54)

    • In vitro and ex vivo implantation of cystine crystals and treatment by contact lens

      2019, Colloids and Surfaces A: Physicochemical and Engineering Aspects
    • Potential role of stromal collagen in cystine crystallization in cystinosis patients

      2018, International Journal of Pharmaceutics
      Citation Excerpt :

      Cystinosis is commonly treated with cysteamine (β-mercaptoethylamine) (Cantani et al., 1983; Gahl et al., 1985; Iwata et al., 1998; Jones et al., 1991; Kimonis et al., 1995; Simpson et al., 2011; Tavares et al., 2009; Thoene et al., 1976; Tsilou et al., 2003) which reacts with intralysosomal cystine to produce mixed disulfide cysteine-cysteamine dimers and the amino acid cysteine (Bradbury et al., 1991; Kaiser-Kupfer et al., 1987, 1990; MacDonald et al., 1990). These are transported out of the lysosome via the lysine transport system, bypassing the damaged cystinosis transporter (Labbe et al., 2009). In the eyes though, a majority of the cystine is extra-cellular, i.e., it is dispersed in the water like stoma layer of the cornea.

    • Ocular Complications of Infantile Nephropathic Cystinosis

      2017, Journal of Pediatrics
      Citation Excerpt :

      There is evidence for crystal accumulation in all layers of the cornea, with cornea stroma involvement being the most significant examination finding. Corneal crystals are typically present in the corneal periphery by 16 months of age, and advance to saturate the cornea by early adolescence if left untreated.7 Although difficult to appreciate on slit-lamp examination, crystals can be visualized in corneal epithelial cells by in vivo confocal microscopy8 and histopathology.6

    • Effect of pH and penetration enhancers on cysteamine stability and trans-corneal transport

      2016, European Journal of Pharmaceutics and Biopharmaceutics
      Citation Excerpt :

      Oral administration favorably treats systemic symptoms [4], but is completely ineffective for ocular manifestations since the cornea, as a consequence of the angiogenic privilege, is an avascular tissue. Therefore, the only possible approach for the effective decrease in corneal cystine crystals responsible for photophobia, keratopathies and frequent corneal erosions [5], is the topical administration of the drug. FDA has recently approved Cystaran™, a cysteamine hydrochloride based eye-drop effective in the reduction in corneal cystine crystals [6].

    View all citing articles on Scopus

    Manuscript no. 2008-1115.

    Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article.

    Supported by Quinze-Vingts National Ophthalmology Hospital, Paris, France.

    View full text