Sir,
Systemic manifestations of congenital rubella syndrome (CRS) include ocular complications (88%), hearing loss (71%), neurologic deficits (75%), and cardiac anomalies (38%).1 Recognition of ocular manifestations is important in making the right diagnosis in patients with late presentation or without full-blown systemic involvement.1, 2 Cataracts, microphthalmia, glaucoma, and ‘salt-and-pepper’ retinopathy were the major ocular features, while rubella keratopathy is less common which might be the sequel of either associated glaucoma or direct viral cytopathologic effect.2 Recent advent of confocal microscopy in delineating corneal pathologies has enchanted in vivo analysis of many corneal diseases at cellular level.3, 4
Case Report
A 20-year-old Chinese man without remarkable paediatric history except sensorineural deafness presented to us in July 2002 with bilateral blurring of vision. Best-corrected visual acuities for the right and left eyes were 20/200 and 20/70, respectively. Intraocular pressure (IOP) was 12 mmHg in each eye. Slit-lamp examination revealed diffuse corneal guttata with ‘beaten-bronze’ appearance. A faint haziness at the stroma was noted but neither Haab's striae nor buphthalmos could be seen. The iris, lens, iridocorneal angles, and corneal sensations were intact. Fundus examination revealed bilateral pigmentary retinopathy and a small juxtafoveal choroidal neovascularization membrane in the left eye (Figure 1a and b). The optic discs and retinal vessels were unremarkable. Small decrement in amplitudes of both scotopic and flicker electroretinogram were noted, suggestive of secondary combined rod and cone involvements. Specular microscopy showed decreased endothelial counts (667 and 712 per square mm in right and left eyes, respectively). Rubella antibody screening by enzyme immunoassay confirmed positive rubella IgG antibody. The loss of hearing, pigmentary retinopathy in this case has already fulfilled World Health Organization recommended case definition for clinically confirmed CRS despite lack of IgM confirmation or other systemic features.5
Confocal microscopy (ASL1000-ModelOS-1, New Orleans, USA) was performed to evaluate for the cause of corneal oedema in the absence of high IOP. The most striking changes lay in the layer of corneal endothelium (Figure 2a). Significant drop in endothelial cell count were observed accompanied by obvious pleomorphism, polymegethism and increased intercellular gaps. Dark endothelial structures with a central bright reflex ‘hollow-out’ lesion might signify a cell dying process or a result of direct viral cytopathy. Presence of intracellular microdeposits might further accentuate this supposition as they may represent endothelial viral inclusion bodies. Anterior stromal examination showed microcystic spaces, delineated fibrous tissue, and relatively normal nerve plexus (Figure 2b).
Deluise et al6 have reported two categories of corneal oedema of different aetiologies in congenital rubella syndrome. The one associated with congenital glaucoma tended to be persistent whereas the corneal oedema in the absence of congenital glaucoma was usually focal with spontaneous resolution within 3–6 months.6 The clinical description of persistent corneal oedema without sine qua non of congenital glaucoma was exceedingly unusual throughout English literatures.6
Patients with CRS may exhibit progressive disease in which cataract, glaucoma, or keratopathy might manifest them later in life.7 Confocal microscopic examination is a noninvasive, superbly reproducible instrument to allow real-time in vivo assessment of the cornea at cellular level.3, 8, 9, 10 The distinctive morphological changes at the endothelium, including cellular irregularities, prominent nuclei, abundant intercellular space, and bright intracellular deposits, advocate the primary disease event residing at endothelium, which can cause subsequent corneal oedema in patients even without IOP elevation.4, 9 These unreported and characteristic in vivo corneal morphological changes may fortify our understanding on rubella keratopathy.
References
Khandekar R, Al Awaidy S, Ganesh A, Bawikar S . An epidemiological and clinical study of ocular manifestations of congenitalrubella syndrome in Omani children. Arch Ophthalmol 2004; 122: 541–545.
Wolf SM . The ocular manifestations of congenital rubella. Trans Am Ophthalmol Soc 1972; 70: 577–614.
Zimmerman LE . Histopathologic basis for ocular manifestations of congenital rubella syndrome. Am J Ophthalmol 1968; 65: 837–862.
Cavanagh HD, Petroll M, Alizadeh H, He YG, McCulley JP, Jester JV et al. Clinical and diagnostic use of in vivo confocal microscopy in patients with corneal disease. Ophthalmology 1993; 100: 1444–1454.
Cutts FT, Best J, Siqueira MM, Engstrom K, Robertson SE . Guidelines for surveillance of congenital rubella syndrome and rubella, field test version, May 1999. Geneva: World Health Organization; 1999. http://www.who.int/vaccines-documents/DocsPDF99/www9934.pdf, WHO.
Deluise VP, Cobo M, Chandler D . Persistent corneal edema in the congenital rubella syndrome. Ophthalmology 1983; 90: 835–839.
Sever JL, South MA, Shaver KA . Delayed manifestations of congenital rubella. Rev Infect Dis 1985; 7(Suppl 1): S164–S169.
De Rojas Silva MV, Diez-Feijoo E, Rodriguez-Ares MT, Sanchez-Salorio M . Confocal microscopy of stage 4 diffuse lamellar keratitis with spontaneous resolution. J Refract Surg 2004; 20: 391–396.
Grupcheva CN, Craig JP, Sherwin T, McGhee CN . Differential diagnosis of corneal oedema assisted by in vivo confocal microscopy. Clin Exp Ophthalmol 2001; 29: 133–137.
Chiou AG, Kaufman SC, Beuerman RW, Ohta T, Yaylali V, Kaufman HE et al. Confocal microscopy in the iridocorneal endothelial syndrome. Br J Ophthalmol 1999; 83: 697–702.
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Liu, D., Law, R., Lau, H. et al. In vivo confocal microscopy in congenital rubella keratopathy. Eye 20, 392–394 (2006). https://doi.org/10.1038/sj.eye.6701870
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DOI: https://doi.org/10.1038/sj.eye.6701870