Curvilinear atrophic streaks in the periphery and the macula have been initially described as the “fourth” sign in presumed ocular histoplasmosis syndrome (POHS).1 Later, these curvilinear abnormalities were often termed Schlaegel lines or linear streaks and have since been observed in multifocal choroiditis, rod-cone dystrophies, and West-Nile retinopathy.2–8 Here we report a case of unilateral curvilinear atrophic lines occurring at the equator of a patient with pseudoxanthoma elasticum. This represents a previously unreported finding in this disease.
A 55-year-old white woman underwent full multimodal imaging at our department for angioid streaks complicated by bilateral choroidal neovascularizations (CNVs). Her past medical history was remarkable for pseudoxanthoma elasticum confirmed by molecular analysis (ABCC6, C.1533 G<A). She previously underwent uneventful cataract surgery in both eyes. She was also under treatment with intravitreal anti-VEGF in both eyes on a pro re nata regimen.
At presentation, her best-corrected visual acuity was 20/40 in the right eye and 20/125 in the left eye; anterior segment was quiet and intraocular pressure within limits. Dilated funduscopic examination disclosed bilateral angioid streaks, peau d'orange, and exudative maculopathy (Figure 1). Examination of the retinal periphery revealed few comet lesions and some focal atrophic spots (salmon spots) in both eyes (Figure 2). In addition, the right eye disclosed curvilinear atrophic lines in the mid-periphery, absent in the fellow eye. Neither vitreous haze nor cells were present. On fundus autofluorescence, these peripheral lines were slightly hyperautofluorescent with some hypoautofluorescence at borders corresponding to pigmentary clumps (Figure 3). Structural optical coherence tomography of these curvilinear abnormalities was not contributory, whereas fluorescein angiography disclosed a corresponding mild hyper- and hypofluorescence (Figure 3). History and charts of the patient were negative for travels to endemic areas for histoplasmosis or previous ocular inflammation. Axial length was 27.78 mm in the right eye and 27.07 mm in the left eye.
Color images and optical coherence tomography (OCT). Color images show angioid streaks with peripapillary scarring, macular neovascularization, peau d'orange, comet lesions, and peripheral punched-out spots; some vitelliform material is visible as a yellowish deposit inferiorly to the fovea in the right eye. The left eye demonstrates a large area of retino-choroidal atrophy inferiorly to the optic disc. The OCT scans illustrate comet lesions in the right eye and the area of retino-choroidal atrophy in the left eye.
Ultra-widefield color and fundus autofluorescence (FAF). Color images (upper panels) and FAF (lower panels) show bilateral angioid streaks, peripapillary atrophy, peau d'orange, peripheral comet lesions and atrophic salmon spots. Besides, the right eye discloses curvilinear atrophic lines parallel to the ora (left panels).
Ultra-widefield fluorescein angiography of the right eye shows macular choroidal neovascularization, angioid streaks, peripapillary atrophy, peripheral comet lesions, and atrophic salmon spots. In addition, curvilinear lines parallel to the ora appear as mild hyper and hypofluorescence.
Ultra-widefield imaging was subsequently reviewed in other 42 eyes of 21 patients affected by pseudoxanthoma elasticum, and no further eyes with peripheral linear streaks at the equator were observed.
Diagnosis of POHS and multifocal choroiditis can be extremely challenging in patients with pseudoxanthoma elasticum. Each condition presents similar signs which may potentially overlap and occur in the absence of significant anterior and vitreous inflammation.1,3 The diagnosis of POHS relies on the presence of three main clinical findings in patients from endemic areas; these include macular lesions (atrophic or fibrovascular), peripapillary scarring and peripheral punched-out spots. However, this set of lesions can similarly occur in pseudoxanthoma elasticum and clinical differentiation is complex even with the aid of multimodal imaging.9,10 On the other hand, whereas the ocular management of POHS and pseudoxanthoma aims at controlling CNVs, multifocal choroiditis may require a different therapeutic approach to tackle subclinical inflammation.11–13 Besides many similar ocular findings, multifocal choroiditis presents episodes of intraocular inflammation fostering disease progression among quiescent periods.3
To our knowledge, peripheral line streaks were reported in both multifocal choroiditis and POHS but not in pseudoxanthoma elasticum. The lines of this patient seemed to have a different origin from that of angioid streaks, which occur more centrally in the inner area of peau d'orange.14,15 In addition, we reviewed ultra-widefield imaging of 42 eyes of 21 patients affected by pseudoxanthoma elasticum (a subset of them from a previous study) and found no other eye with similar findings.16 Apparently, these findings may support a clinical diagnosis of an overlapping retinal disease like multifocal choroiditis. However, Schlaegel lines could also be incidental and aspecific findings, as equatorial “sword-like lesions” described in non-inflammatory conditions.7 Interestingly, Spaide well outlined how these lines were not pathognomonic signs of multifocal choroiditis or POHS and observed that many patients with these lines were myopic as our case.3 Their peculiar position and shape may also suggest perfusion abnormalities of watershed zones of choroidal circulation. At that location blood flow is supplied by both anterior and posterior choroidal arteries, and their watershed zone lies at the equator.17
In conclusion, the pathogenesis of these curvilinear lines is still unknown, and their presence in pseudoxanthoma elasticum could be an incidental finding or a sign of an overlapping disease. Nevertheless, further studies are required to confirm that these equatorial atrophic lines parallel to the ora are not part of the clinical spectrum of pseudoxanthoma elasticum. Furthermore, if retinal inflammation develops in pseudoxanthoma elasticum, it is of paramount importance to choose the most appropriate anti-inflammatory therapy. The treatment should fit the increased cardiovascular risk associated with this disease, particularly when planning chronic therapies.
- Fountain JA, Schlaegel TF Jr, . Linear streaks of the equator in the presumed ocular histoplasmosis syndrome. Arch Ophthalmol. 1981;99(2):246–248. doi:10.1001/archopht.1981.03930010248004 [CrossRef]
- Parodi MB. Progressive subretinal fibrosis in fundus flavimaculatus. Acta Ophthalmol. 1994;72(2):260–264. doi:10.1111/j.1755-3768.1994.tb05027.x [CrossRef]
- Spaide RF, Yannuzzi LA, Freund KB. Linear streaks in multifocal choroiditis and panuveitis. Retina. 1991;11(2):229–231. doi:10.1097/00006982-199111020-00008 [CrossRef]
- Matsumoto Y, Francis JH, Yannuzzi LA. Curvilinear streaks in multifocal choroiditis. Eur J Ophthalmol. 2007;17(3):448–450. doi:10.1177/112067210701700332 [CrossRef]
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- Khairallah M, Ben Yahia S, Attia S, et al. Linear pattern of West Nile virus-associated chorioretinitis is related to retinal nerve fibres organization. Eye (Lond). 2007;21:952–955. doi:10.1038/sj.eye.6702355 [CrossRef]
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- Gliem M, Zaeytijd JD, Finger RP, Holz FG, Leroy BP, Charbel Issa P. An update on the ocular phenotype in patients with pseudoxanthoma elasticum. Front Genet. 2013;4:14. doi:10.3389/fgene.2013.00014 [CrossRef]
- Nielsen JS, Fick TA, Saggau DD, Barnes CH. Intravitreal anti-vascular endothelial growth factor therapy for choroidal neovascularization secondary to ocular histoplasmosis syndrome. Retina. 2012;32(3):468–472. doi:10.1097/IAE.0b013e318229b220 [CrossRef]
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- Marchese A, Rabiolo A, Corbelli E, Carnevali A, Cicinelli MV, Giuffrè C, Querques G, Bandello F. Ultra-widefield imaging in patients with angioid streaks secondary to pseudoxanthoma elasticum. Ophthalmology Retina. 2017;1(2):137–144. doi:10.1016/j.oret.2016.10.005 [CrossRef]
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