Oleander-Associated Keratitis and Uveitis.

PURPOSE: Oleander is a poisonous plant with extensively documented systemic side effects; however, oleander's ophthalmic side effects have not been detailed in the literature. We report a case of oleander-associated keratitis with subsequent corneal edema and anterior uveitis. METHODS: This is a case report and review of relevant literature. RESULTS: A 58-year-old woman presented with large corneal epithelial defect after being struck in the eye with an oleander leaf. Despite treatment with topical moxifloxacin, she developed severe corneal edema and anterior uveitis. A diagnosis of oleander-associated ocular inflammation with secondary corneal edema was made, given the temporal relationship, and treatment was initiated with topical prednisolone and cyclopentolate. However, the corneal edema and inflammation continued to progress until oral prednisone and topical difluprednate were initiated. Visual acuity, anterior uveitis, and corneal edema significantly improved with aggressive immunomodulation. Follow-up at 1 month confirmed complete recovery of symptoms, corneal edema and anterior uveitis. CONCLUSIONS: Severe corneal edema and anterior uveitis can be associated with oleander exposure. Aggressive treatment with oral and topical steroids may be required without persistent sequelae at the 5-month follow-up. Ophthalmologists should consider this inflammatory reaction if patients experience ocular exposure to oleander.

Precision Molecular Diagnosis Defines Specific Therapy in Combined Immunodeficiency with Megaloblastic Anemia Secondary to MTHFD1 Deficiency.

BACKGROUND: Methylenetetrahydrofolate dehydrogenase (MTHFD1) deficiency has recently been reported to cause a folate-responsive syndrome displaying a phenotype that includes megaloblastic anemia and severe combined immunodeficiency. OBJECTIVE: To describe our investigative approach to the molecular diagnosis and evaluation of immune dysfunction in a family with MTHFD1 deficiency. METHODS: The methods used were exome sequencing and analysis of variants in genes involved in the folate metabolic pathway in a family with 2 affected siblings. Routine laboratory and research data were analyzed to gain an in-depth understanding of innate, humoral, and cell-mediated immune function before and after folinic acid supplementation. RESULTS: Interrogation of exome data for concordant variants between the siblings in the genes involved in folate metabolic pathway identified a heterozygous mutation in exon 3 of the MTHFD1 gene that was shared with their mother. In view of highly suggestive phenotype, we extended our bioinformatics interrogation for structural variants in the MTHFD1 gene by manual evaluation of the exome data for sequence depth coverage of all the exons. A deletion involving exon 13 that was shared with their father was identified. Routine laboratory data showed lymphopenia involving all subsets and poor response to vaccines. In vitro analysis of dendritic cell and lymphocyte function was comparable to that in healthy volunteers. Treatment with folinic acid led to immune reconstitution, enabling discontinuation of all prophylactic therapies. CONCLUSIONS: Exome sequencing demonstrated MTHFD1 deficiency as a novel cause of a combined immunodeficiency. Folinic acid was established as precision therapy to reverse the clinical and laboratory phenotype of this primary immunodeficiency.