Identification and characterization of a new pathologic mutation in a large Leber hereditary optic neuropathy pedigree.

BACKGROUND: Most patients suffering from Leber hereditary optic neuropathy carry one of the three classic pathologic mutations, but not all individuals with these genetic alterations develop the disease. There are different risk factors that modify the penetrance of these mutations. The remaining patients carry one of a set of very rare genetic variants and, it appears that, some of the risk factors that modify the penetrance of the classical pathologic mutations may also affect the phenotype of these other rare mutations. RESULTS: We describe a large family including 95 maternally related individuals, showing 30 patients with Leber hereditary optic neuropathy. The mutation responsible for the phenotype is a novel transition, m.3734A > G, in the mitochondrial gene encoding the ND1 subunit of respiratory complex I. Molecular-genetic, biochemical and cellular studies corroborate the pathogenicity of this genetic change. CONCLUSIONS: With the study of this family, we confirm that, also for this very rare mutation, sex and age are important factors modifying penetrance. Moreover, this pedigree offers an excellent opportunity to search for other genetic or environmental factors that additionally contribute to modify penetrance.

Spontaneous resolution of inflammatory epiretinal membrane: Case series and review of the literature.

Epiretinal membrane (ERM) represents a common complication of uveitis that may contribute independently to vision loss in patients with uveitis. Although spontaneous idiopathic ERM separation has been previously reported, to the best of our knowledge there are only two case reports in the scientific literature that depicts spontaneous regression of an inflammation-associated ERM. Spontaneous ERM separation is a rare but possible event, which occurs most often subsequent to posterior vitreous detachment. We present a case series of three patients with uveitis that exhibit the formation and subsequent spontaneous resolution of an inflammatory ERM.

Clinical Testing of Head Impulse Paradigm and Suppression Head Impulse Paradigm Using a Diagnostic Headband: Combined Clinical Sign for Improved Performance.

OBJECTIVE: We developed a clinical sign that improves the sensitivity, specificity, and predictive values of the Head Impulse Paradigm (HIMP) Test by adding the Suppression Head Impulse Paradigm (SHIMP) Test using a diagnostic headband. METHODS: Prospective and descriptive study analyzing the function of 1,255 horizontal semicircular canals of subjects with differing vestibulo-ocular reflex (VOR) gains who showed-up with symptoms related to neurotology (Montevideo, Uruguay, March 2017 to March 2019). The clinical HIMP and SHIMP tests were assessed and the amplitudes of overt saccades were compared to each other. Clinical findings were contrasted against vHIT gains. CONCLUSION: The HIMP and SHIMP combined test using the H/S headband has high specificity and low sensibility. This test association can identify healthy individuals among individuals typically misdiagnosed as ill by the conventional HIT or HIMP maneuver of the HIMP test, as originally described by Halmagyi and Curthoys. Therefore, we recommend using the headband assisted HIMP/SHIMP test, instead of exclusively relying on positive HIMP results.

A Single Dose of Nitrate Increases Resilience Against Acidification Derived From Sugar Fermentation by the Oral Microbiome.

Tooth decay starts with enamel demineralization due to an acidic pH, which arises from sugar fermentation by acidogenic oral bacteria. Previous in vitro work has demonstrated that nitrate limits acidification when incubating complex oral communities with sugar for short periods (e.g., 1-5 h), driven by changes in the microbiota metabolism and/or composition. To test whether a single dose of nitrate can reduce acidification derived from sugar fermentation in vivo, 12 individuals received a nitrate-rich beetroot supplement, which was compared to a placebo in a blinded crossover setting. Sucrose-rinses were performed at baseline and 2 h after supplement or placebo intake, and the salivary pH, nitrate, nitrite, ammonium and lactate were measured. After nitrate supplement intake, the sucrose-induced salivary pH drop was attenuated when compared with the placebo (p < 0.05). Salivary nitrate negatively correlated with lactate production and positively with ΔpH after sucrose exposure (r= -0.508 and 0.436, respectively, both p < 0.05). Two additional pilot studies were performed to test the effect of sucrose rinses 1 h (n = 6) and 4 h (n = 6) after nitrate supplement intake. In the 4 h study, nitrate intake was compared with water intake and bacterial profiles were analysed using 16S rRNA gene Illumina sequencing and qPCR detection of Rothia. Sucrose rinses caused a significant pH drop (p < 0.05), except 1 h and 4 h after nitrate supplement intake. After 4 h of nitrate intake, there was less lactate produced compared to water intake (p < 0.05) and one genus; Rothia, increased in abundance. This small but significant increase was confirmed by qPCR (p < 0.05). The relative abundance of Rothia and Neisseria negatively correlated with lactate production (r = -0.601 and -0.669, respectively) and Neisseria positively correlated with pH following sucrose intake (r = 0.669, all p < 0.05). Together, these results show that nitrate can acutely limit acidification when sugars are fermented, which appears to result from lactate usage by nitrate-reducing bacteria. Future studies should assess the longitudinal impact of daily nitrate-rich vegetable or supplement intake on dental health.

Brimonidine-induced unilateral ocular lichen planus: a case report / Líquen plano ocular unilateral induzido por brimonidina: relato de caso

ABSTRACT This report was written to describe a case of unilateral brimonidine-induced conjunctival lichen planus. Because the ophthalmic examination indicated chronic conjunctivitis or drug-induced pseudopemphigoid, the patient underwent thorough ophthalmic and systemic examinations, as well as conjunctival biopsy and direct immunofluorescence studies. A 71-year-old woman with unilateral left eye findings of chronic conjunctivitis was referred to our Ophthalmology Department. The patient reported that chronic conjunctivitis began shortly after she initiated use of topical brimonidine. Ophthalmic examination revealed foreshortening of the inferior fornix and symblepharon. Conjunctival biopsy revealed submucous lymphocytes and shaggy distribution of fibrinogen on direct immunofluorescence; this was suggestive of ocular lichen planus. No other systemic lesions were found that were consistent with the presentation of lichen planus. A good response was observed to topical cyclosporine treatment. To our knowledge, this may be the first report of unilateral ocular lichen planus without systemic findings. The correlation with the initiation of topical brimonidine suggests that this might be the first case of biopsy-confirmed brimonidine-induced ocular lichen planus.

RESUMO Este relato é para descrever um caso de líquen plano conjuntival unilateral induzido por brimonidina. Como o exame oftalmológico indicava conjuntivite crônica ou pseudopenfigóide induzido por medicamento, o paciente foi submetido a exames oftalmológicos e sistémicos completos, além de biópsia conjuntival e estudos de imunofluorescência direta. Uma mulher de 71 anos de idade com achados unilaterais do olho esquerdo de conjuntivite crônica foi encaminhada ao nosso departamento de Oftalmologia. A paciente relatou que a conjuntivite crônica começou logo após o início do uso da brimonidina tópica. O exame oftalmológico revelou encurtamento do fórnice inferior e do symblepharon. A biópsia conjuntival revelou linfócitos submucosos e distribuição felpuda de fibrinogênio na imunofluorescência direta; isso era sugestivo de líquen plano ocular. Não foram encontradas outras lesões sistêmicas compatíveis com a apresentação do líquen plano. Uma boa resposta foi observada no tratamento tópico com ciclosporina. Pelo nosso conhecimento, este pode ser o primeiro relato de líquen plano ocular unilateral sem achados sistêmicos. A correlação com o início da brimonidina tópica sugere que este pode ser o primeiro caso de líquen plano ocular induzido por brimonidina confirmado por biópsia.

Brimonidine-induced unilateral ocular lichen planus: a case report.

This report was written to describe a case of unilateral brimonidine-induced conjunctival lichen planus. Because the ophthalmic examination indicated chronic conjunctivitis or drug-induced pseudopemphigoid, the patient underwent thorough ophthalmic and systemic examinations, as well as conjunctival biopsy and direct immunofluorescence studies. A 71-year-old woman with unilateral left eye findings of chronic conjunctivitis was referred to our Ophthalmology Department. The patient reported that chronic conjunctivitis began shortly after she initiated use of topical brimonidine. Ophthalmic examination revealed foreshortening of the inferior fornix and symblepharon. Conjunctival biopsy revealed submucous lymphocytes and shaggy distribution of fibrinogen on direct immunofluorescence; this was suggestive of ocular lichen planus. No other systemic lesions were found that were consistent with the presentation of lichen planus. A good response was observed to topical cyclosporine treatment. To our knowledge, this may be the first report of unilateral ocular lichen planus without systemic findings. The correlation with the initiation of topical brimonidine suggests that this might be the first case of biopsy-confirmed brimonidine-induced ocular lichen planus.