Fundus imaging in Danon’s disease

A 70-year-old female with Danon’s disease (LAMP2 heterozygous pathogenic variant c.467T>G), status post-cardiac transplantation, presented with 4 years of progressive peripheral visual field disturbances, photophobia, and prolonged dark adaptation. Visual acuity was 20/30 OD and 20/40 OS. Examination revealed pseudophakia OU, and diffuse retinal pigmentary changes [Fig. 1a and 1b]. Widefield fundus autofluorescence (FAF) imaging demonstrated slightly asymmetric diffuse irregularity of the FAF signal [Fig. 1a and b]. Macular optical coherence tomography (OCT) showed outer band irregularities, nodular retinal pigment epithelium (RPE) thickening, and thin choroid [Fig. 1c and d]. Electroretinography (ERG) demonstrated a moderate cone-rod pattern of generalized photoreceptor dysfunction, worse in the left eye [Fig. 2a-d], and superior visual field constriction OU [Fig. 2e and 2f].Figure 1: Multimodal retinal imaging from a 70/F with Danon’s disease showing retinal pigmentary changes and widespread fundus autofluorescence abnormalities (a and b) on ultra-wide field imaging (inset). Optical coherence tomography (OCT) shows outer band irregularities, nodular retinal pigment epithelium thickening (orange arrow), and choroidal thinning (c and d)Figure 2: Light-adapted single flash electroretinogram (ERG) from the right eye (a) and left eye (b) shows a severe reduction in response amplitude. Dark-adapted ERG from the right (c) and left (d) eyes similarly demonstrates subnormal response amplitudes, consistent with global cone- and rod-system dysfunction. Left eye responses were affected more than those of the right eye. Semiautomated kinetic perimetry (e and f) reveals superior constriction and more severe disease in the left eye (e), compared to the right eye (f)Discussion Danon’s disease (OMIM #300257) was first described by Danon et al. in 1981 as a cardiomyopathy caused by structural dysfunction in a lysosomal protein.[1] Additional systemic findings include skeletal myopathy and intellectual disability.[2] Ophthalmic manifestations, reported sparsely, were described much later after the discovery of the disease. Findings include a pigmentary retinopathy, lens changes, ERG abnormalities with cone and rod dysfunction, and visual field changes. Due to X-linked inheritance, males experience more severe disease, often requiring cardiac transplantation by early adulthood, and a limited lifespan.[3] Our patient exhibited extensive peripheral involvement, likely attributable to her age. Her FAF pattern showed mixed hyper- and hypo-autofluorescence, similar to patterns seen in carriers of other X-linked disorders like retinitis pigmentosa and choroideremia.[4] The asymmetry may reflect variable X-chromosome inactivation. Notably, ocular signs may precede serious cardiac disease, underscoring the importance of early eye and genetic evaluation.[5] Authors contributions Sakshi Shiromani: concept, design, literature search, data acquisition, manuscript preparation. Anika Quillin: literature search, data acquisition, manuscript editing, and review. Nieraj Jain: concept, design, data acquisition, definition of intellectual content, manuscript editing, and review Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship: Foundation Fighting Blindness Career Development Award CD-C-0918-0748-EEC (NJ); Research to Prevent Blindness Challenge Grant; National Eye Institute P30EY00630; Sitaraman Family. Conflicts of interest: There are no conflicts of interest.