Persistent diffuse photoreceptor disorganization: further evidence with potential associations, long-term clinical course and therapeutic responsiveness of a new clinical entity

Background Recently, a novel clinical picture associated with characteristic, progressive alterations in the ellipsoid zone (EZ) and thinning of the outer retinal layers referred to as Persistent Diffuse Photoreceptor Disorganization (PDPD) was first described. Methods We performed detailed longitudinal clinical assessments in five patients with PDPD, i.e. ophthalmological examinations, including imaging (optical coherence tomography (OCT), fundus autofluorescence, dye angiography) and functional diagnostics (best-corrected visual acuity (BCVA), visual field, electroretinography), comparative genomic sequencing analysis and further examinations. Results The patients (3 female, 2 male) were between 21 and 60 years old. All developed bilateral involvement sequentially, with the interval between symptom onset in the first and second eye ranging from 8.2 months to 139.5 months. All patients showed characteristic blurred EZ and absent interdigitation zone followed by thinning of the outer retinal layers. Comparative genomic sequencing analysis yielded no (likely) pathogenic variants in genes that could be associated. We saw no clear response to steroid treatment. Most recent BCVA was below 20/80 Snellen equivalent in 9/10 eyes and 20/25 in one eye. Conclusion We add further evidence and additional clinical data to the newly recognized disease PDPD. In our cohort, PDPD presents with subacute, bilateral but sequential vision loss, accompanied by positive visual symptoms (e.g. crossfade) and characteristic OCT changes, including progressive blurring of the EZ beginning in the foveola, followed by outer retinal thinning starting in the parafovea. The etiology remains unclear, and it is uncertain whether anti-inflammatory treatment can modify the disease-course, which resulted in severe visual impairment in the majority of patients.