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Middle East African Journal of Ophthalmology Middle East African Journal of Ophthalmology
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Year : 2013  |  Volume : 20  |  Issue : 1  |  Page : 77-79  

In vivo confocal microscopy in chloroquine-induced keratopathy

Department of Oto-Neuro-Ophthalmological Surgical Sciences, Eye Clinic, University of Florence, Policlinic of Careggi, Viale Morgagni 85, 50134, Florence, Italy

Date of Web Publication23-Jan-2013

Correspondence Address:
Iacopo Paladini
Department of Oto-Neuro-Ophthalmological Surgical Sciences - Eye Clinic, Viale GB Morgagni 85, 50134 Florence
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0974-9233.106397

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In vivo confocal microscopy is becoming a mandatory examination to study corneal abnormalities such as drug deposits in systemic disease. A female diagnosed with fibromyalgia on systemic chloroquine for 9 months presented for an ophthalmic examination. Confocal microscopy was performed using the Confoscan 4 (Nidek Co. Ltd., Gamagori, Japan) and multiple highly reflective deposits in the epithelial basal cells were found, that were consistent with choloquine. Deposits were also present in the wing cell layer. In the anterior stroma these deposits were rare. Atypically shaped and branched nerves were also present in the anterior stroma. Corneal deposits of chloroquine can be evaluated by confocal microscopy. Confocal microscopy provides information on corneal metabolism and physiology. Chloroquine keratopathy can affect the anterior stroma in addition to the epithelium.

Keywords: Chloroquine, Confocal Microscopy, Cornea, Fibromyalgia

How to cite this article:
Paladini I, Menchini U, Mencucci R. In vivo confocal microscopy in chloroquine-induced keratopathy. Middle East Afr J Ophthalmol 2013;20:77-9

How to cite this URL:
Paladini I, Menchini U, Mencucci R. In vivo confocal microscopy in chloroquine-induced keratopathy. Middle East Afr J Ophthalmol [serial online] 2013 [cited 2021 Nov 27];20:77-9. Available from: http://www.meajo.org/text.asp?2013/20/1/77/106397

   Introduction Top

Fibromyalgia is a syndrome characterized by chronic widespread musculoskeletal pain and stiffness in association with fatigue and poor sleep. The classification of the American College of Rheumatology Criteria for fibromyalgia includes the presence of pain in all four body quadrants in combination with excess tenderness to manual palpation in at least 11 of 18 muscle-tendon sites, in the absence of clinically demonstrable peripheral nociceptive causes. [1] Although some biological mechanisms have been identified, the etiology and pathogenesis of fibromyalgia remain unclear. [2],[3]

The prevalence of FMS in the general population is estimated to be between 1.3% and 4.8%. [4] Chloroquine can be prescribed for management of this syndrome. However the potential for ocular toxicity due to chloroquine therapy is well documented. [5] Confocal microscopy is one method to evaluate the corneal toxicity of chloroquine. The clinical application of confocal microscopy in ophthalmology dates back to the 1960s. Over the time confocal microscopy has been used to study the structural morphology of ocular tissues such as the cornea and to monitor changes that occur with time.

This case report presents a relatively uncommon application of confocal microscopy for evaluating corneal toxicity in a patient taking systemic chloroquine for fibromyalgia.

   Case Report Top

A 64-year-old Caucasian female was referred by her rheumatologist. She had a medical history of fybromyalgia that had been diagnosed in December 2008. In November 2009 the patient began treatment with a daily dose of 250 mg of chloroquine bisphosphonate (Clorochina, Bayer Italia, Milano, Italy) for 9 months. The only ocular symptom was modest dry eye that was controlled with artificial tears.

At presentation, the fybromialgia was well controlled. The only significant findings on slit-lamp biomicroscopy were corneal deposits and vortex keratopathy (cornea verticillata) [Figure 1]. Uncorrected visual acuity was 0.0 LogMAR in the right eye and 0.0 LogMAR in the left eye. Intraocular pressure (IOP) was 13 mm Hg bilaterally and the fundus examination was unremarkable. The patient was examined using a scanning slit corneal confocal white-light microscopy Confoscan 4 (Nidek Co. Ltd., Gamagori, Japan), with a ×40 lens. Confoscan 4 was used to study the corneal morphology and assess layer reflectivity and cellular density.
Figure 1: Slit lamp biomicroscopy: fine corneal deposits

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The main parameters for the acquisition sequence were set with a z-axis range of movement of 1000 μm, thus giving a theoretical z-axis distance between images in the scans of 10 μm. Each frame is approximately 400×300 μm (area, 0.12 mm 2 ). The position on the z-axis of the corneal thickness of each image was obtained using the Z-Scan function of the instrument. The Z-Scan is a graph that plots the depth (expressed in microns) on the x-axis and the level of reflectivity (expressed in arbitrary numerical units called light reflectance units, LRU) on the y-axis, of each corneal image included in the scan.

Oxibuprocaine cloridrate 0.4% was instilled in each eye (Novesina 0, 4%, Novartis Farma, Origgio, Italy), than a drop of polyacrylic acid 0.2% (Viscotirs gel, Medivis, Catania, Italy) was placed on the microscope probe as a coupling agent to avoid epithelial damage.

   Results Top

Confocal microscopy


No chloroquine deposits were observed on the endothelium of both eyes. Polymegathism and pleomorphism were detected that were likely age related [Figure 2]a.
Figure 2: (a) Endothelium: no chloroquine deposits were observed, (b) Deep stroma: no chloroquine deposits were observed, (c) Anterior stroma: chloroquine deposits were rarely represented

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Deep stroma

No chloroquine deposits were observed in the deep stroma bilaterally [Figure 2]b.

Anterior stroma

Chloroquine deposits were rare in the anterior stroma [Figure 2]c.


Some anterior stromal nerves with an atypical shape, branches, and a thinner diameter were present [Figure 3]a.
Figure 3: (a) Nerves: few anterior stromal nerves with atypical shape and branches and thinner diameter, (b) Epithelium: chloroquine deposits were detectable in epithelium. The cells lost their well-marked borders because of the reflectivity of the drug deposits

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Chloroquine deposits were detectable in the basal and intermediate layers. The cells lost their well-marked borders due to the reflectivity of drug deposits [Figure 3]b.

   Discussion Top

Systemic medication use may lead to deposition of some components in different tissues. Although chloroquine is not the gold standard for treatment of fibromyalgia and similar inflammatory diseases, it is a reasonable alternative for many cases. Drugs from the chloroquine family (chloroquine, hydroxychloroquine, amodiaquine) may produce ocular toxicity involving the cornea (vortex keratopathy), ciliary body, lens (posterior subcapsular cataracts), and retina (bull's eye maculopathy). [5] Corneal deposits are usually located in the epithelium and the anterior stroma, intracellularly within lysosomes. [6],[7]

Confocal microscopy provides histologic sections of corneal tissue. Hence, confocal microscopy is an important method to evaluate the distribution of chloroquine (or other medications for inflammatory disease) in the cornea. [8],[9] In vivo confocal microscopy of patients treated with hydroxychloroquine has shown formation of corneal inclusion bodies in the anterior stroma that are likely to be phagocytosed by activated keratocytes, causing these cells to be highly reflective. [9]

In this case report, we found the presence of hyperflective deposits in the basal and intermediate epithelium corneal cells. These inclusions measured between 2 and 12 μm. Some bright microdots were detected in the anterior stroma indicating keratocyte activation. Some anterior stromal nerves appeared thinner than normal and convoluted suggesting that chloroquine could affect neural structures also.

The histologic sections of corneal tissue in vivo using confocal microscopy are a very useful method to study corneal architecture. Future applications of confocal microscopy will include the study of corneal metabolism. This case report is one of a handful of imaging studies of corneal deposits due to cholorquine evaluated by confocal microscopy. Comparison of future studies to this case report may be helpful in evaluation of similar keratopathies.

   References Top

1.Wolfe F, Smythe HA, Yunus MB, Bennett RM, Bombardier C, Goldenberg DL, et al. The American College of Rheumatology 1990 criteria for the classification of fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum 1990;33:160-72.  Back to cited text no. 1
2.Laske C, Stransky E, Eschweiler GW, Klein R, Wittorf A, Leyhe T, et al. Increased BDNF serum concentration in fibromyalgia with or without depression or antidepressants. J Psychiatr Res 2007;41:600-5.  Back to cited text no. 2
3.Yunus MB. Towards a model of pathophysiology of fibromyalgia: Aberrant central pain mechanisms with peripheral modulation. J Rheumatol 1992;19:846-50.  Back to cited text no. 3
4.Biewer W, Conrad I, Häuser W. [Fibromyalgia]. Schmerz 2004;18:118-24.  Back to cited text no. 4
5.Hirst LW, Sanborn G, Green WR, Miller NR, Heath WD. Amodiaquine ocular changes. Arch Ophthalmol 1982;100:1300-4.  Back to cited text no. 5
6.Slowik C, Somodi S, von Gruben C, Richter A, Guthoff R. [Detection of morphological corneal changes caused by chloroquine therapy using confocal in vivo microscopy]. Ophthalmologe 1997;94:147-51.  Back to cited text no. 6
7.Pülhorn G, Thiel HJ. [Ultrastructural aspects of chloroquin-keratopathy (author's transl)]. Albrecht Von Graefes Arch Klin Exp Ophthalmol 1976;201:89-99.  Back to cited text no. 7
8.Paladini I, Menchini U, Mencucci R. Corneal chrysiasis: In vivo confocal microscopy analysis. Eur J Ophthalmol 2010;20:776-9.  Back to cited text no. 8
9.Dosso A, Rungger-Brändle E. In vivo confocal microscopy in hydroxychloroquine-induced keratopathy. Graefes Arch Clin Exp Ophthalmol 2007;245:318-20.  Back to cited text no. 9


  [Figure 1], [Figure 2], [Figure 3]

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