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We recommend regular monitoring for ophthalmological manifestations of JS beginning soon after birth or diagnosis. We demonstrate delayed visual development and note that the amblyogenic time frame may last significantly longer in JS than is typical. In general, patients with coloboma were less likely to display retinal degeneration, and those with retinal degeneration did not have coloboma. Severe retinal degeneration that is early and aggressive is seen in disease caused by specific genes, such as CEP290- and AHI1-associated JS. Retinal degeneration in INPP5E-, MKS1-, and NPHP1-associated JS was generally milder. Finally, ptosis surgery can be helpful in a subset of patients with JS; decisions as to timing and benefit/risk ratio need to be made on an individual basis according to expert consultation.

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Ocular manifestations of cobalamin C deficiency include a developmental as well as a degenerative phenotype and lack strict correlation to metabolic status, but may be mitigated by prenatal or early treatment. Purpose To explore the ocular manifestations of cobalamin C (cblC) deficiency, an inborn error of intracellular vitamin B12 metabolism caused by mutations in the MMACHC gene. Design Retrospective, observational case series. Participants Twenty-five cblC patients underwent clinical and ophthalmic examination at the National Institutes of Health Clinical Center between August 2004 and September 2012. Patient ages ranged from 2 to 27 years at last ophthalmic visit, and follow-up ranged from 0 to 83 months (median, 36 months; range, 13–83 months) over a total of 69 visits. Methods Best-corrected Snellen visual acuity, slit-lamp biomicroscopy, dilated fundus examination, wide-field photography, fundus autofluorescence imaging, sedated electroretinography, spectral-domain optical coherence tomography, and metabolite assessment. Main Outcome Measures Visual acuity and presence and degree of retinal degeneration and optic nerve pallor. Results Nystagmus (64%), strabismus (52%), macular degeneration (72%), optic nerve pallor (68%), and vascular changes (64%) were present. c.271dupA (p.R91KfsX14) homozygous patients (n = 14) showed early and extensive macular degeneration. Electroretinography showed that scotopic and photopic responses were reduced and delayed, but were preserved remarkably in some patients despite severe degeneration. Optical coherence tomography images through the central macular lesion of a patient with severe retinal degeneration showed extreme thinning, some preservation of retinal lamination, and nearly complete loss of the outer nuclear layer. Despite hyperhomocysteinemia, no patients exhibited lens dislocation. Conclusions This longitudinal study reports ocular outcomes in the largest group of patients with cblC deficiency systematically examined at a single center over an extended period. Differences in progression and severity of macular degeneration, optic nerve pallor, and vascular attenuation between homozygous c.271dupA (p.R91KfsX14) patients and compound heterozygotes were noted. The pace and chronicity of ophthalmic manifestations lacked strict correlation to metabolic status as measured during visits. Prenatal or early treatment, or both, may have mitigated ocular disease, leading to better functional acuity, but patients still progressed to severe macular degeneration. The effects of prenatal or early treatment, or both, in siblings, the manifestation of severe disease in infancy, the presence of comorbid developmental abnormalities (e.g., microcephaly, cardiac noncompaction), and the possible laminar structural defect noted in many patients are findings showing that cblC deficiency displays a developmental as well as a degenerative ocular phenotype.