Structural Abnormalities of the Inner Macula in Incontinentia Pigmenti

Abstract

ncontinentia pigmenti (IP), or Bloch-Sulzberger syndrome, is a rare X-linked dominant disorder mainly seen in females because a single allele in male embryos is usually fatal. 1,2 Incontinentia pigmenti usually presents with a characteristic skin rash that leaves hypopigmented patches on the trunk and limbs. 3 The most serious events involve the retina and central nervous system (CNS) in 18% to 30%. [2][3][4][5] Loss-offunction mutations in IKBKG/NEMO impair nuclear factorkappa B (NF-κB) signaling and are responsible for most cases of IP. 6,7 Although NF-κB signaling is ubiquitous, effects from the IKBKG/NEMO mutation do not manifest in all tissues.Vision loss has been associated with vascular occlusions, secondary extraretinal neovascularization (NV), tractional retinal detachments, 2,5,8 and foveal hypoplasia. 8 Herein, we report findings from spectral-domain optical coherence tomography (SD-OCT) in children with IP examined before age 5 years. Poor visual behavior corresponded with inner retinal structural abnormalities.IMPORTANCE This report presents evidence from spectral-domain optical coherence tomography and fluorescein angiography of inner foveal structural abnormalities associated with vision loss in incontinentia pigmenti (IP).OBSERVATIONS Two children had reduced visual behavior in association with abnormalities of the inner foveal layers on spectral-domain optical coherence tomography. Fluorescein angiography showed filling defects in retinal and choroidal circulations and irregularities of the foveal avascular zones. The foveal to parafoveal ratios were greater than 0.57 in 6 eyes of 3 patients who had extraretinal neovascularization and/or peripheral avascular retina on fluorescein angiography and were treated with laser. Of these, 3 eyes of 2 patients had irregularities in foveal avascular zones and poor vision.CONCLUSIONS AND RELEVANCE Besides traction retinal detachment, vision loss in IP can occur with abnormalities of the inner foveal structure seen on spectral-domain optical coherence tomography, consistent with prior descriptions of foveal hypoplasia. The evolution of abnormalities in the neural and vascular retina suggests a vascular cause of the foveal structural changes. More study is needed to determine any potential benefit of the foveal to parafoveal ratio in children with IP. Even with marked foveal structural abnormalities, vision can be preserved in some patients with IP with vigilant surveillance in the early years of life.

Assessment of the Retinal Structure in Children With Incontinentia Pigmenti

“…These findings were consistent over 5 clinical visits at ages 1 month, 2 months, 6 months, 1.2 years and 2.5 years. Interestingly, contrary to a previous report that the retinal thinning was observed after laser photocoagulation, 11 this patient showed thinning of the retinal layers at the first visit at 1 month of age prior to laser treatment. These findings were stable for years after laser treatment, indicating that peripheral laser photocoagulation did not affect inner or outer macular retinal thinning.…”

“…Similar to those reported by Basilius et al 11 , we visualized inner retinal layer thinning in 2 of our participants. Both children showed extensive areas of peripheral retinal non-perfusion.…”

“…In 2015, Basilus et al published the first report on OCT findings in IP in four children under 5 years of age. 11 The present report adds additional reports of microanatomical changes observed in seven children with IP by SDOCT.…”

“…16 However, these findings of stable non-foveal retinal thinning also raise the possibility that despite 20/20 optotype visual acuity, subtle visual functional abnormalities may be present and delineated by future visual field testing and microperimetry testing. In addition both we and Basilius et al 11 failed to find RPE abnormalities associated with such areas of thinning. Thus, we postulate that, as proposed by Goldberg et al, 4 the neural tissue changes in the retina are secondary to vascular events and not secondary to abnormalities originating in the RPE.…”

“…Reported eye manifestations of IP are diverse, and include amaurosis, strabismus and nystagmus, retinal anomalies such as retinal detachment, retinal vascular abnormalities (hemorrhage, neovascularization, avascularity of the retina), retinal pigment epithelium abnormalities and lens changes. 2, 3, 5, 6, 8 The first report of the use of SDOCT imaging in IP 11 in 2015 has tremendously increased our insight into structural abnormalities in the retina that are not visualized during a routine ophthalmic examination. However, little is known about the pathogenesis of these retinal anomalies.…”