When compared with classic RP, generally defined by pigment deposits in the mid periphery along with retinal atrophy, the fundi of patients with biallelic variants in
CFAP410 most often show double hyperautofluorescence rings, as well as degeneration concentrated in the vascular arcades. Unlike concentric RP,
21 which tends to show better BCVA and photoreceptor responses in the ERG than typical RP, patients with biallelic variants in
CFAP410 show a worse BCVA and associated macular atrophy. The ellipsoid zone in patients with
CFAP410 mutations needs further quantitative study to confirm whether there is a difference among concentric RP, typical RP, and
CFAP410-related RP. In addition, hyperautofluorescence rings inside the macular vascular arcades are common in Stargardt disease, and double concentric autofluorescence rings including a perimacular ring and another ring within the vascular arcades have been described in patients with
NR2E3-associated RP.
22 Thus, double autofluorescence rings inside and outside of the vascular arcades might be considered as a peculiar sign of
CFAP410-related retinopathy, as shown in the present study, especially combined with posterior staphyloma. Additionally, the outer hyperfluorescence ring was invisible in two older patients at 26 years of age. Double hyperautofluorescence rings could be seen in the early stage of
CFAP410 related retinal disorder in the younger patients from our cohort. It was suspicious that the fundus changes of single of hyperautofluorescence ring are characteristic of progressive stage of the disease and changes of hyperautofluorescence rings were followed at patients in who were their 40s or older. Gene-specific fundus changes have been reported for other genes, such as nummular pigment deposits for
CRB1,
23 diffuse mottled hypopigmentation for
SPATA7,
24 more severe atrophy of the parafovea than the fovea region for
RDH12,
25 and discontinuous pigment deposits from macular and peripheral retina for
PROM1.
26 As the genes expressed in the cilia of photoreceptors,
CFAP410-associated retinopathy shared some similarity with those caused by other genes, like
IQCB1 and
CEP290,
27–29 such as tapetoretinal degeneration without obvious pigmentation in most cases. In addition, other key ciliopathy-associated proteins, including SPATA7, RPGRIP1, and NEK1, might interact with CFAP410. Clinically, biallelic variants in
SPATA7 cause RP, with well-preserved macular and yellowish–white frosted retinal degeneration concentrated in the midperiphery.
24 Patients with variants in
RPGRIP1 share similar fundus changes with
CFAP410, including varying macular atrophy, mottled pigmentary changes, and quadrant aggravated retinal degeneration.
30 Previous studies have also shown an interaction between
SPATA7 and
RPGRIP1.31,32 In patients with variants in
NEK1, a mottled ellipsoid band on optical coherence tomography images corresponds with the ring of hyperautofluorescence on fundus autofluorescence images.
33 The correlation about the retinal degeneration edge and fundus autofluorescence double hyperautofluorescence rings needs further clarification based on the known association between
NEK1 and
CFAP410.34 However, skeletal manifestations, including a narrowed thorax, pectus carinatum, and shortening of the metacarpal, have also been described in patients with
CFAP410 mutations in previous studies,
3,4,20 but rarely were seen in our patients. The pathogenic mechanisms responsible for the ocular degeneration and skeletal dysplasia also needs to be clarified.