A 54-year-old man with bilateral symmetrical circular corneal opacities
Digital Journal of Ophthalmology 2020
Volume 26, Number 2
June 21, 2020
DOI: 10.5693/djo.03.2019.12.001
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Colm McAlinden, MD, MB BCh, BSc (Hons), MSc, PhD, MRCOphth | Department of Ophthalmology, Princess of Wales Hospital, Bridgend, United Kingdom
Christopher P. R. Williams, BSc (Hons), MB BCh (Hons), MRCP, FRCOphth | Department of Ophthalmology, Princess of Wales Hospital, Bridgend, United Kingdom


History
A 54-year-old man was referred to the Princess of Wales Hospital, Bridgend, United Kingdom, for evaluation of corneal opacities found on routine eye examination. He was asymptomatic and had no history of contact lens wear. Past ophthalmic, medical, and drug history were unremarkable. Of note, the patient reported having taken various brands of multivitamins over the preceding 3 years. He did not smoke tobacco, but he had a history of smoking cannabis in the past. He denied alcohol excess. The patient reported that his siblings and mother all had recent eye examinations and no signs of corneal opacities. His mother denied drug use during pregnancy. The patient was observed over a period of 2 months, with no change in appearance of the stromal opacities.

Examination
On examination, unaided visual acuity was 20/20 in each eye. Slit-lamp examination revealed bilateral, symmetrical, circular, gray-white stromal opacities in the midperipheral cornea measuring 5 mm in diameter. The width of the ring was approximately 0.5 mm. Corneal sensation was normal, and there was no corneal vascularization or epithelial defects. The anterior chamber was deep and quiet, with no iris transillumination in either eye. Intraocular pressure by Goldmann applanation tonometry was 16 mm Hg in each eye. There was minimal nuclear sclerosis in each eye. Funduscopy was unremarkable apart from a small choroidal nevus in the right eye.

Ancillary Testing
Anterior segment imaging was acquired, including photography (Figure 1), optical coherence tomography (Triton; Topcon, Tokyo, Japan), and Pentacam HR (Oculus, Wetzlar, Germany). See Figures 2-3. Optical coherence tomography scans of the macula and optic disc were normal in both eyes. Extensive blood investigations were ordered, including urea and electrolytes, full blood count, liver function, bone profile, random glucose, C-reactive protein, erythrocyte sedimentation rate, Borrelia burgdorferi antibodies, lipid panel (including apolipoprotein A-1), serum protein electrophoresis, antinuclear antibody, caeruloplasmin, angiotensin converting enzyme, ferritin, transferrin, transferrin saturation, iron, and heavy metal screen for lead and copper. Urine amino acids, glycosaminoglycan, creatinine, and glycosaminoglycan:creatinine ratio were also ordered to exclude gross amino acid disorders and mucopolysaccharidoses. Blood and urine testing revealed no significant abnormalities. Because infectious etiology was deemed unlikely, corneal cultures were not acquired.

Figure 1
 Slit-lamp photograph of the right eye showing intrastromal corneal circular opacity.

Figure 2
 Optical coherence tomography image demonstrating the stromal opacity sparing the epithelium and endothelium.

Figure 3
 Scheimpflug Pentacam HR image demonstrating the stromal opacity sparing the epithelium and endothelium.

Treatment
Because the work-up was negative and the condition was nonprgogressive, the patient was observed.

Differential Diagnosis
The differential diagnosis for corneal opacities is broad (see Table 1). History, examination, and investigations should narrow this significantly; however, one should consider previous trauma, infection (acanthamoeba keratitis, herpetic keratitis, or interstitial keratitis), inflammation (Wessely immune ring) or Cogan syndrome. Cogan syndrome is a rare vasculitic condition causing intraocular inflammation and vestibuloauditory dysfunction, typically affecting young adults. Anterior and posterior embryotoxon is also on the differential list, both producing ring like corneal opacities. Coats white ring is usually associated with previous corneal foreign body. Drug deposition as well as metabolic disorders are major differential diagnoses, both of which must be carefully considered. Common drug offenders causing corneal deposition include amiodarone, chloroquine, hydroxychloroquine, tamoxifen, chlorpromazine, silver, gold, and amantadine. Metabolic disorders associated with corneal changes include Wilson’s disease and lysosomal storage disorders (eg, cystinosis, mucopolysaccharidosis, and Fabry disease). Finally, some stromal dystrophies can cause circular corneal opacification (eg, Schnyder corneal dystrophy).

Table 1
 Differential diagnosis of circular/ring-shaped corneal opacities

Table 1 (cont.)

Diagnosis and Discussion
This unusual presentation of circular stromal opacities was comprehensively investigated, and no identifiable cause was found. Only a small number of similar idiopathic cases have been reported in the literature,(1) the first being described by Ascher in 1963.(2)

The absence of corneal vascularization and symmetrical appearance may point more toward a degeneration or dystrophy, such as a phenotypic variation of a stromal dystrophy, with perhaps the most similar being Schnyder corneal dystrophy.(7) The degenerations of crocodile shagreen and Vogt’s limbal girdle differ in appearance, as does the Hudson-Stähli line in iron deposition, Stocker’s line in keratoconus, and posterior embryotoxon.

Other alternative considerations are immunological and infective responses such as Coats white ring, Wessely immune ring, Gram-negative rods, fungi, herpes simplex/zoster, and Acanthamoeba. However, none of these fit the history and clinical features of the present case. Other differentials include immunoglobulin deposition as part of a multiple myeloma, which was excluded in our case.(8)

Corneal opacities may be secondary to a wide array of etiologies, including trauma, infection, or inflammation. They may also result from drug deposition, metabolic disorders, and corneal dystrophies or degenerations. It is important in such rare presentations to take an accurate history and to arrange appropriate investigations. The perfect circular shape and isolation in the midperipheral cornea suggest that this case likely represents deposition from an unknown material.

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