Pathogenic STX3 variants affecting the retinal and intestinal transcripts cause an early-onset severe retinal dystrophy in microvillus inclusion disease subjects.

Biallelic STX3 variants were previously reported in five individuals with the severe congenital enteropathy, microvillus inclusion disease (MVID). Here, we provide a significant extension of the phenotypic spectrum caused by STX3 variants. We report ten individuals of diverse geographic origin with biallelic STX3 loss-of-function variants, identified through exome sequencing, single-nucleotide polymorphism array-based homozygosity mapping, and international collaboration. The evaluated individuals all presented with MVID. Eight individuals also displayed early-onset severe retinal dystrophy, i.e., syndromic-intestinal and retinal-disease. These individuals harbored STX3 variants that affected both the retinal and intestinal STX3 transcripts, whereas STX3 variants affected only the intestinal transcript in individuals with solitary MVID. That STX3 is essential for retinal photoreceptor survival was confirmed by the creation of a rod photoreceptor-specific STX3 knockout mouse model which revealed a time-dependent reduction in the number of rod photoreceptors, thinning of the outer nuclear layer, and the eventual loss of both rod and cone photoreceptors. Together, our results provide a link between STX3 loss-of-function variants and a human retinal dystrophy. Depending on the genomic site of a human loss-of-function STX3 variant, it can cause MVID, the novel intestinal-retinal syndrome reported here or, hypothetically, an isolated retinal dystrophy.

Topiramate-induced palinopsia: a case series and review of the literature.

BACKGROUND: To report palinopsia as a possible side effect of topiramate. METHODS: Case series and review of the literature. RESULTS: Nine patients in our series, and 4 previously reported patients, who developed palinopsia while on topiramate, are reviewed. All patients were women, and comorbidities included migraine, idiopathic intracranial hypertension, and bulimia nervosa. Palinopsia resolved in 8 patients after stopping or decreasing the dose of topiramate. The lowest dose of topiramate causing palinopsia was 25 mg twice a day. More than half of our patients reported exacerbation of visual disturbance in early morning or late evening. CONCLUSIONS: Topiramate-induced palinopsia may be underdiagnosed because physicians do not inquire about such visual symptoms.

Ophthalmic manifestations of tetrasomy 18p.

PURPOSE: To characterize ophthalmic findings in patients with tetrasomy 18p, a rare chromosomal anomaly that has been previously associated with strabismus. METHODS: All subjects underwent a complete eye examination to screen for ocular pathology. RESULTS: A total of 25 subjects (13 female) were examined after they were diagnosed with tetrasomy 18p. The average age of subjects was 8.2 years (range, 13 months to 22 years). Of the 25 subjects, 18 (72% of examined subjects, 42% of the cohort) showed evidence of strabismus; 16 had esotropia (8 uncategorized, 5 infantile, and 3 accommodative), 1 had esophoria, and 1 was diagnosed with intermittent exotropia. CONCLUSIONS: The coincidence of esotropia with tetrasomy 18p indicates the need to routinely screen these patients for strabismus at the time of diagnosis.

Occlusion properties of prosthetic contact lenses for the treatment of amblyopia.

BACKGROUND: The efficacy of opaque contact lenses as occlusion therapy for amblyopia has been established in the literature. Prosthetic contact lenses use similar tints to improve cosmesis in scarred or deformed eyes and may be an alternative in occlusion therapy. To test this idea, we determined the degree of vision penalization elicited by prosthetic contact lenses and their effect on peripheral fusion. METHODS: We tested 19 CIBA Vision DuraSoft 3 Prosthetic soft contact lenses with varying iris prints, underprints, and opaque pupil sizes in 10 volunteers with best-corrected Snellen distance visual acuity of 20/20 or better in each eye. Snellen visual acuity and peripheral fusion using the Worth 4-Dot test at near were measured on each subject wearing each of the 19 lenses. RESULTS: Results were analyzed with 3-factor analysis of variance. Mean visual acuity through the various lenses ranged from 20/79 to 20/620. Eight lenses allowed preservation of peripheral fusion in 50% or more of the subjects tested. Iris print pattern and opaque pupil size were significant factors in determining visual acuity (p < 0.05). CONCLUSIONS: Sufficient vision penalization can be achieved to make occlusion with prosthetic contact lenses a viable therapy for amblyopia. The degree of penalization can be varied and different iris print patterns and pupil sizes, using peripheral fusion, can be preserved with some lenses. Prosthetic contact lenses can be more cosmetically appealing and more tolerable than other amblyopia treatment modalities. These factors may improve compliance in occlusion therapy.

Optic neuritis after anthrax vaccination.

OBJECTIVE: To report the occurrence of optic neuritis after anthrax vaccination in two patients. DESIGN: Observational case reports, review of literature. METHODS: Description of clinical history, examination, neuroimaging, and further studies in two patients experiencing optic neuritis in temporal association with anthrax vaccination. MAIN OUTCOME MEASURES: Visual acuity, visual fields. RESULTS: Two patients, 39 and 23 years of age, were seen with acute optic neuritis 1 month and 2 weeks, respectively, after anthrax booster vaccination and successfully treated with intravenous methylprednisolone. The first patient had a typical presentation and course of unilateral retrobulbar optic neuritis with excellent visual recovery. The second patient had a bilateral anterior optic neuritis and has required chronic immunosuppression to maintain his vision. Retinal and optic nerve autoantibodies were present in the second patient. No cross-reactive epitopes between anthrax vaccine and retina/optic nerve were identified. CONCLUSION: Optic neuritis is a potential adverse reaction of anthrax vaccination.