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Novel Compound Heterozygous Mutations Resulting in Cone Letters seemed to be dark. The narrowing of the retinal vessels and disc 2. Kline LB, Kelly CL. Ocular migraine in a patient with cluster headaches. pallor diminished gradually over time. In the late phase of the Headache. 1980;20(5):253-257. attack (after 1 minute 28 seconds), the retinal vessels were di- 3. Winterkorn JMS, Kupersmith MJ, Wirtschafter JD, Forman S. Brief report: treatment of vasospastic amaurosis fugax with calcium-channel blockers. N Engl lated and the disc was hyperemic. Video 2 and Video 3 show J Med. 1993;329(6):396-398. the reperfusion of the retinal circulation in the late phase. The 4. Bernard GA, Bennett JL. Vasospastic amaurosis fugax. Arch Ophthalmol. images obtained immediately after the attack (Figure 2) show 1999;117(11):1568-1569. the dilated retinal vessels in the right eye. The images show that 5. Hill DL, Daroff RB, Ducros A, Newman NJ, Biousse V. Most cases labeled as the retinal veins and arteries in the right eye were more di- “retinal migraine” are not migraine. J Neuroophthalmol. 2007;27(1):3-8. lated than those in the left eye (not shown) or those obtained 6. Petzold A, Islam N, Plant GT. Video reconstruction of vasospastic transient under normal conditions 1 month after the attack. monocular blindness. N Engl J Med. 2003;348(16):1609-1610. No hypercoagulability was identified with hematologic and serologic testing. Findings on neurologic tests and magnetic Novel Compound Heterozygous Mutations Resulting resonance imaging of the brain were normal. The patient was in Cone Dystrophy With Supernormal Rod Response treated with propranolol hydrochloride because of an allergy Cone dystrophy with supernormal rod response (CDSRR) to lomerizine hydrochloride, and the retinal migraines have (RCD3B, OMIM #610356) was first described in 2 siblings by not recurred. Gouras et al1 in 1983. In subsequent reports, it has been char- acterized as a rare autosomal recessive retinal disorder asso- Discussion | Most cases of previously documented retinal va- ciated with a delayed and markedly decreased cone and rod sospasms have been associated with emboli or systemic response that exhibits an exaggerated, or superthreshold, rod diseases.1,3,4 Most cases reported to be retinal migraine were electroretinogram (ERG) in response to higher stimulus levels.2 cases of presumed retinal vasospasm, and this disorder is ex- Reports of CDSRR commonly describe an early onset of dys- ceedingly rare.5 Because our patient had no systemic disease chromatopsia, photophobia, and central scotoma with poor except migraine and no embolus, the attacks were likely to have best-corrected visual acuity.3 Associated signs and symp- been primary vasospasms. The images clearly show vaso- toms include nyctalopia, nystagmus, and macular retinal pig- spasm in a patient with a history of migraine with aura, which ment epithelium changes.3,4 supports the belief that retinal migraine is a distinct entity. In- Genetic studies have linked CDSRR to mutations in the po- dividual cases of transient monocular vision loss have varied tassium channel, subfamily V,member 2 gene (KCNV2), which in the main component of vasoconstriction.6 In our case, dif- is predominantly expressed in retinal photoreceptors and en- fuse narrowing of the retinal vessels may have represented de- codes a modulatory subunit of the Kv8.2 voltage-gated potas- creased blood flow in the central retinal artery, and disc pal- sium channel.4 Mutations in KCVN2 may inhibit proper as- lor and a dark choroid may have indicated decreased posterior sembly of heteromeric voltage-gated potassium channels with ciliary circulation. Therefore, we speculated that the main com- a subsequent pathologically prolonged outward potassium cur- ponent of the vasoconstriction may be the ophthalmic artery rent in the dark, causing an abnormality in photoreceptor mem- and that marked retinal vasodilation at the end and immedi- brane potentials.5 The exclusive link of CDSRR to KCNV2 mu- ately after the attack may represent compensation for hy- tations is a notable contrast from the majority of inherited poxia of the retinal tissues. retinal disorders, which display genetic heterogeneity. Isao Ota, MD, PhD Methods | A complete ophthalmic examination by a retinal phy- Kiyomi Kuroshima, MD sician (S.H.T.) was performed, including fundus autofluores- Taiji Nagaoka, MD, PhD cence using scanning laser ophthalmoscopy (Heidelberg reti- nal angiograph; Heidelberg Engineering), microperimetry (MP1; Author Affiliations: Department of Ophthalmology, Asahikawa Red Cross Nidek Technologies), and spectral-domain optical coherence Hospital, Asahikawa, Japan (Ota); Department of Neurology, Asahikawa Red tomography (Spectralis optical coherence tomography/ Cross Hospital, Asahikawa, Japan (Kuroshima); Department of Ophthalmology, Asahikawa Medical University, Asahikawa, Japan (Nagaoka). scanning laser ophthalmoscopy; Heidelberg Engineering). An Corresponding Author: Isao Ota, MD, PhD, Department of Ophthalmology, electrophysiological assessment was performed using the Es- Asahikawa Red Cross Hospital, 1-1 Akebono, Asahikawa, 070-8530, Japan pion 5 system (Diagnosys). Full-field electroretinograms (ERGs) ([email protected]). were recorded according to the standards of the International Published Online: September 5, 2013. Society for Clinical Electrophysiology of Vision. doi:10.1001/jamaophthalmol.2013.4686. Blood samples were genetically screened at Casey Eye In- Author Contributions: Study concept and design: All authors. stitute Laboratory, Portland, Oregon, for KCVN2 coding re- Acquisition of data: Ota, Kuroshima. Analysis and interpretation of data: Ota, Kuroshima. gion mutations that cause disease. All exons and flanking in- Drafting of the manuscript: All authors. trons of KCVN2 were directly sequenced on the ABI 3100XL Critical revision of the manuscript for important intellectual content: Ota. DNA sequencer (Applied Biosystems), and detected variants Obtained funding: Ota. Administrative, technical, or material support: Ota, Kuroshima. were analyzed for evolutionary conservation by the predic- Study supervision: Nagaoka. tion programs PolyPhen-2 and SIFT. Conflict of Interest Disclosures: None reported. 1. Humphrey WT. Central retinal artery spasm. Ann Ophthalmol. Report of a Case | A 47-year-old man presented with decreased 1979;11(6):877-881. visual acuity and a history of hemeralopia and photophobia 1482 JAMA Ophthalmology November 2013 Volume 131, Number 11 jamaophthalmology.com Copyright 2013 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/30/2021 Letters Figure 1. Color Photographs, Fundus Autofluorescence Images, and Optical Coherence Tomographic Images A B C D E F Color photographs of the right (A) and left (B) eyes demonstrate bilateral images of the right (C) and left (D) eyes demonstrate hypoautofluorescent macular atrophy (dotted inset) with pale optic nerves with peripapillary atrophy areas suggestive of central atrophy with a surrounding ring of (white arrowheads) and diffuse retinal pigment epithelial changes. There was hyperautofluorescence corresponding to lipofuscin accumulation in the retinal also a significant amount of asteroid hyalosis (black arrowhead) in the right eye pigment epithelium likely secondary to incomplete degradation of (A). These magnified images of the macula highlight the graduated atrophy photoreceptor outer segments. These autofluorescence findings correlate with corresponding to the bright deposits around the fovea in both eyes (A and B) retinal optical coherence tomographic imaging of the right (E) and left (F) eyes exhibiting a hyperreflective crystalline appearance. Fundus autofluorescence showing diffuse outer retinal atrophy bilaterally. for several years. Medical, ocular, and family histories were un- domain optical coherence tomography revealed diffuse outer remarkable. Best-corrected visual acuity was 20/150 OD and retinal atrophy as evidenced by loss of inner segment–outer 20/100 OS. Pupils, extraocular movements, confrontational vi- segment continuity and loss of outer nuclear layer–outer plexi- sual fields, intraocular pressures, and anterior segment ex- form layer normal architecture as well as granular changes cor- amination findings were within normal limits. Color vision was responding to the hyperreflective crystalline lesions seen on diminished to 3/6 on Hardy-Rand-Rittler plates in both eyes. fundus examination (Figure 1E and F). Mean full-field ERG re- On fundus examination, there was bilateral macular atro- sults and respective stereotypical tracings showed signifi- phy with retinal pigment epithelium changes and pale optic cant delays and amplitudinal loss in the photopic cone and nerves with peripapillary atrophy (Figure 1A and B). The right 30-Hz flicker ERGs indicating generalized cone system dys- eye had moderately dense asteroid hyalosis (Figure 1A). Fun- function (Figure 2). Bipolar cell-corresponding b-waves were dus autofluorescence demonstrated bilateral patchy, central reduced compared with the photoreceptor-specific a-wave. The hypoautofluorescence surrounded by a ring of high-density hy- dim-flash, scotopic rod ERGs (0.01 candela · s/m2) showed pro- perautofluorescence in the macula (Figure 1C and D). Spectral- foundly delayed b-waves, and the bright-flash, maximum cone jamaophthalmology.com JAMA Ophthalmology November 2013 Volume 131, Number 11 1483 Copyright 2013 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/30/2021 Letters
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