Loss of function of RIMS2 causes a syndromic congenital cone-rod synaptic disease with neurodevelopmental and pancreatic involvement

Congenital cone-rod synaptic disorder (CRSD), also known as incomplete congenital stationary night blindness (iCSNB), is a non-progressive inherited retinal disease (IRD) characterized by night blindness, photophobia, and nystagmus, and distinctive electroretinographic features. Here, we report bi-allelic RIMS2 variants in seven CRSD-affected individuals from four unrelated families. Apart from CRSD, neurodevelopmental disease was observed in all affected individuals, and abnormal glucose homeostasis was observed in the eldest affected individual. RIMS2 regulates synaptic membrane exocytosis. Data mining of human adult bulk and single-cell retinal transcriptional datasets revealed predominant expression in rod photoreceptors, and immunostaining demonstrated RIMS2 localization in the human retinal outer plexiform layer, Purkinje cells, and pancreatic islets. Additionally, nonsense variants were shown to result in truncated RIMS2 and decreased insulin secretion in mammalian cells. The identification of a syndromic stationary congenital IRD has a major impact on the differential diagnosis of syndromic congenital IRD, which has previously been exclusively linked with degenerative IRD

Accuracy of formulae for secondary intraocular lens power calculations in pediatric aphakia

Purpose: To compare the accuracy of axial length vergence formulas versus refractive vergence formulas for secondary intraocular lens (IOL) implantation in pediatric aphakia. Methods: This retrospective comparative study, evaluated 31 eyes of 31 patients aged ≤3.5 years, who had undergone secondary IOL implantation. The median absolute error (MedAE) was compared between axial length vergence formulas (Hoffer Q, Holladay I, SRK II, and SRK/T) and refractive vergence formulas (Lanchulev, Holladay R, Mackool, and Khan) as well as between formulas within the same vergence. Results: There was a significant difference (P = 0.010) between MedAE for axial length vergence formulas [1.19 Diopter(D)] and MedAE for refractive vergence formulas (2.48 D). The MedAE of axial length vergence formulas were comparable as to Hoffer (1.59 D), Holladay (1.27 D), SRK/T (1.23 D), and SRK II (1.30 D). Among refractive vergence formulas, Lanchulev (5.00 D) and Holladay R (2.51 D) had significantly larger MedAE as compared to Khan (2.06 D) and Mackool (2.15 D). Conclusion: Axial length vergence formulas performed significantly better than refractive vergence formulas; however, axial length vergence formulas were comparable within the same vergence. Keywords: Axial length, Refractive, Intraocular lens, Pediatric, Aphakia, Intraocular lens power calculatio