Serial ERG monitoring of response to therapy in vitamin A deficiency related night blindness.

Two male patients with known systemic disorders who presented with complaints of nyctalopia underwent a complete ophthalmic examination including electrophysiological evaluation and serum vitamin A (retinol) levels. A significant vitamin A deficiency was detected, supplementation started and repeat electroretinogram (ERG) testing was carried out to monitor the timeline of recovery. Restoration of rod and generalised cone function was rapid within the first week of receiving treatment and near normal recovery was seen after 1 month of supplementation. Serial monitoring of ERG changes in vitamin A deficiency (VAD) associated night blindness plays an important role to demonstrate functional recovery post-treatment. The different effects of VAD on rod and cone function, and their rate of recovery, may reflect differences in the visual cycle between the two photoreceptors. We report the serial ERG changes in VAD related night blindness secondary to intestinal lipofuscinosis and liver cirrhosis in two patients.

Acquired night blindness due to rod dysfunction after long-term hemodialysis.

PURPOSE: To report the clinical findings in 6 patients who developed night blindness after long-term hemodialysis. STUDY DESIGN: Retrospective case series. PATIENTS AND METHODS: The medical charts of the 6 patients were examined. The fundus photographs, spectral-domain optical coherence tomographic (SD-OCT) images, full-field ERGs, and blood chemistry panels were analyzed. RESULTS: The mean age of the 6 patients (4 men) at the time of diagnosis was 69.1 ± 5.9 years. The mean duration of the hemodialysis was 21.8 ± 13.4 years (7-41 years). The visual acuity of the patients was preserved at 20/30 or better except in 1 eye. Ophthalmoscopy showed white flecks that were scattered over the midperipheral retina in all the eyes. SD-OCT showed mild macular degeneration in 5 eyes. The scotopic ERGs elicited by dim flashes were absent, and those elicited by bright flashes had negative waveforms. The photopic ERGs were relatively well preserved. These data indicated a rod-specific dysfunction that may account for the night blindness. The plasma concentration of vitamin A was within the normal range in 4 of the patients and slightly lower than the normal limit in 1 of the patients. Administration of vitamin A was performed for 1 patient, and the symptom of night blindness and scotopic ERGs were improved 3 months later. DISCUSSION: Long-term hemodialysis can be associated with the night blindness that may be caused by vitamin A deficiency, even though the plasma concentration of vitamin A in these patients was within the normal range.

High-resolution photoreceptor imaging analysis of patients with autosomal dominant retinitis pigmentosa (adRP) caused by HK1 mutation.

PURPOSE: The hexokinase 1 (HK1) gene encodes one of the four human hexokinases that play essential roles in glucose metabolism. Recently, several cases of E847K mutation in the HK1 gene were reported to cause inherited retinal dystrophy. The purpose of this study was to identify the phenotypical characteristics of patients with a recurrent E847K mutation in the HK1 gene. METHODS: Three generations of one family with autosomal dominant retinitis pigmentosa were examined. Whole exome sequencing was performed on the DNA. Fundus imaging by an adaptive optics fundus camera was used to obtain high-resolution photoreceptor images. RESULTS: Fundus examination of the proband showed degeneration of the mid-peripheral retina, and SD-OCT images showed an absence of the ellipsoid zone (EZ) and interdigitation zone (IZ) in the parafovea and more peripherally. SD-OCT images of the mother of the proband showed an absence of the EZ and IZ, and fundus autofluorescence images showed hypo-autofluorescence surrounding the macular region. One daughter of the proband had only mild night blindness, however, the density of the cone photoreceptors was reduced in the parafoveal region. Whole exome sequencing identified a heterozygous variant, E847K, in the HK1 gene. This variant was found to co-segregate with the disease in three family members. CONCLUSIONS: Although the systemic phenotypes were found to be associated with the HK1 mutations, only the E847K mutation can cause a non-syndromic photoreceptor degeneration. Our study strengthened the hypothesis that the amino acid E847 might play a critical role in the maintenance of the morphology and function of the photoreceptors.

[Clinical phenotype and genotype analysis of the family with the Usher syndrome].

OBJECTIVE: To detect potential variants in a family affected with Usher syndrome type I, and analyze its genotype-phenotype correlation. METHODS: Clinical data of the family was collected. Potential variants in the proband were detected by high-throughput sequencing. Suspected variants were verified by Sanger sequencing. RESULTS: The proband developed night blindness at 10 year old, in addition with bilateral cataract and retinal degeneration. Hearing loss occurred along with increase of age. High-throughput sequencing and Sanger sequencing revealed that she has carried compound heterozygous variants of the MYO7A gene, namely c.2694+2T>G and c.6028G>A. Her sister carried the same variants with similar clinical phenotypes. Her daughter was heterozygous for the c.6028G>A variant but was phenotypically normal. CONCLUSION: The clinical features and genetic variants were delineated in this family with Usher syndrome type I. The results have enriched the phenotype and genotype data of the disease and provided a basis for genetic counseling.

Retinal degeneration in mice expressing the constitutively active G90D rhodopsin mutant.

Rhodopsin is the G protein-coupled receptor in rod photoreceptor cells that initiates vision upon photon capture. The light receptor is normally locked in an inactive state in the dark by the covalently bound inverse agonist 11-cis retinal. Mutations can render the receptor active even in the absence of light. This constitutive activity can desensitize rod photoreceptor cells and lead to night blindness. A G90D mutation in rhodopsin causes the receptor to be constitutively active and leads to congenital stationary night blindness, which is generally thought to be devoid of retinal degeneration. The constitutively active species responsible for the night blindness phenotype is unclear. Moreover, the classification as a stationary disease devoid of retinal degeneration is also misleading. A transgenic mouse model for congenital stationary night blindness that expresses the G90D rhodopsin mutant was examined to better understand the origin of constitutive activity and the potential for retinal degeneration. Heterozygous mice for the G90D mutation did not exhibit retinal degeneration whereas homozygous mice exhibited progressive retinal degeneration. Only a modest reversal of retinal degeneration was observed when transducin signaling was eliminated genetically, indicating that some of the retinal degeneration occurred in a transducin-independent manner. Biochemical studies on purified rhodopsin from mice indicated that multiple species can potentially contribute to the constitutive activity causing night blindness.

Usher syndrome in a patient with Ellis-van Creveld syndrome.

PURPOSE: To describe a case of Ellis-van Creveld syndrome with concomitant Usher syndrome. METHODS: A 24-year-old lady with a diagnosis of Ellis-van Creveld syndrome came to our attention in 2015 complaining of nyctalopia. She underwent yearly ophthalmologic examinations, including visual acuity, dilated fundoscopy, optical coherence tomography and colour fundus photography. RESULTS: On the day of her first examination, her visual acuity was 20/20, whereas fundus examination revealed diffuse peripheral retinal atrophy with pigmented bone spicules, waxy pallor of the disc and macular sparing in both eyes, compatible with retinitis pigmentosa. Due to the severe retinitis pigmentosa phenotype for the age and the concomitant neurosensory hearing loss, ancillary electrophysiological and genetic tests were requested. At the end of follow-up, visual function remained stable, with electroretinogram tests confirming the peripheral dysfunction. Interestingly, next generation sequencing test revealed a mutation in USH2A gene, suggestive of an overlapping Usher syndrome. On optical coherence tomography angiography, all plexuses appeared altered, with some degree of impairment also in the choriocapillaris of the spared macula. CONCLUSION: Our report emphasizes the advantage of new genetic tests to investigate atypical presentations of known retinal disorders found in syndromic settings. In addition, we speculate that the underlying ciliopathy might possibly aggravate the phenotype of this case of Usher syndrome.

Melanoma-associated retinopathy.

Melanoma-associated retinopathy (MAR) is a rare paraneoplastic autoimmune manifestation of cutaneous malignant melanoma. Patients classically present with acute onset night blindness, positive visual phenomena and visual field defects, and typically have significantly reduced quality of life as a result. Early recognition of MAR is of prognostic significance as it can precede the diagnosis of primary or metastatic malignant melanoma, and early treatment can lower the risk of irreversible immunological damage to the retinal cells with improved visual outcomes. The focus of our review article is therefore to raise awareness of MAR and present the latest evidence relating to the investigation and management of this condition.

An Ashkenazi Jewish founder mutation in CACNA1F causes retinal phenotype in both hemizygous males and heterozygous female carriers.

Background: Mutations in CACNA1F have been mainly associated with X-linked incomplete congenital stationary night blindness (icCSNB). Variable phenotypic expression in females was reported in some families. We report here three non-related Ashkenazi Jewish families originating in Eastern Europe, that included males and a many affected females, initially diagnosed with variable retinal phenotypes.Materials and Methods: Whole exome sequencing (WES), Sanger sequencing and microsatellite haplotyping were used for genetic analysis. Complete ophthalmologic examination was performed including visual acuity, refraction, colour vision, slit-lamp, fundoscopy and electroretinography (ERG).Results: We identified four affected males, showing moderate visual impairment, and seven female carriers, six of them presenting mild to moderate visual impairment. Infantile nystagmus was found in all affected males and in 5/7 females. Nyctalopia and myopia were common in both males and females. Initial clinical differential diagnosis included cone-dystrophy, cone-rod dystrophy, cone-dystrophy with supernormal rod response or CSNB based on ERG results. WES and Sanger sequencing revealed a previously described missense mutation c.2225T>G; p.(F742C) in CACNA1F (NM_001256789.2) in all three families, encompassed by a shared haplotypeConclusions: Our data suggests that p.(F742C) in CACNA1F is an X-linked founder mutation in Ashkenazi Jews originating in Eastern Europe. This mutation causes a mild-to-moderate icCSNB phenotype, expressed in most female carriers. A targeted test for this variant in suspected patients may initiate diagnostic analysis. Our results highlight the relevance of WES in the clinic, allowing fast and accurate diagnosis for unclear and variable clinical phenotype and in pedigrees with multiple possible inheritance patterns.

Night Blindness in Cystic Fibrosis: The Key Role of Vitamin A in the Digestive System.

Vitamin A is a fundamental micronutrient that regulates various cellular patterns. Vitamin A deficiency (VAT) is a worldwide problem and the primary cause of nocturnal blindness especially in low income countries. Cystic fibrosis (CF) is a known risk factor of VAD because of liposoluble vitamin malabsorption due to pancreatic insufficiency. We describe a case of a 9-year-old girl who experienced recurrent episodes of nocturnal blindness due to profound VAD. This little girl is paradigmatic for the explanation of the key role of the gut-liver axis in vitamin A metabolism. She presents with meconium ileus at birth, requiring intestinal resection that led to a transient intestinal failure with parenteral nutrition need. In addition, she suffered from cholestatic liver disease due to CF and intestinal failure-associated liver disease. The interaction of pancreatic function, intestinal absorption and liver storage is fundamental for the correct metabolism of vitamin A.

A Novel Mutation in the Choroideremia Gene in a Turkish Family.

Choroideremia is an X-linked recessive genetic disorder caused by mutations in the CHM gene. It is a rare retinal dystrophy that manifests as nyctalopia and vision loss, progressing to blindness in later stages. We report a 21-year Turkish man who presented with nyctalopia for the past 4-5 years. His mother and maternal grandmother had similar, but less pronounced complaints. Fundus examination revealed pigmentary changes and retinal atrophy in both eyes. Optical coherence tomography showed outer retinal loss, with central island of preserved autofluorescence surrounded by absent autofluorescence on fundus autofluorescence examination. Goldmann visual fields were constricted. Microperimetry detected retinal sensitivity losses, and full-field electroretinogram demonstrated extinguished cone responses. Genetic analysis revealed a novel nonsense mutation in the CHM gene, namely p.E480X: c.1438G >T. The mutation causes a premature stop codon in exon 12. This is the first report of a G1438T mutation resulting in an E480X premature stop in the CHM gene.

Case Report: Delayed Vitamin A Retinopathy Secondary to Bariatric Surgery.

SIGNIFICANCE: Although rare, vitamin A retinopathy should be considered by the clinicians in their differentials for conditions that can lead to nyctalopia, especially in those patients who have undergone bariatric surgery. Patients must be educated on this potential delayed adverse effect of the surgery and possible lifelong vitamin A supplementation. PURPOSE: The purpose of this study was to report a rare case of delayed vitamin A retinopathy that occurred because of vitamin A malabsorption secondary to bariatric surgery. CASE REPORT: A 55-year-old woman presented with nyctalopia and dark adaptation problems. The patient had a history of gastric bypass surgery 22 years earlier. Fundus examination revealed a large number of small white dots in the midperiphery of both eyes. Electrophysiology testing revealed flat-lined scotopic responses. Vitamin A levels were found to be severely reduced. Subsequent vitamin A supplementation resulted in the reversal of all signs and symptoms. CONCLUSIONS: This case report demonstrates the importance of considering vitamin A deficiency in patients who present with symptoms of nyctalopia with a history of bariatric surgery. Clinicians should be aware of a possible delayed onset and refer for appropriate testing and treatment, as vitamin A retinopathy has been shown to be reversible. Because other conditions can present with nyctalopia and retinal white spots, clinicians also need to consider the appropriate differential diagnoses. Lifelong monitoring is indicated because reoccurrences have been reported.

Night-vision aid using see-through display for patients with retinitis pigmentosa.

PURPOSE: From an early stage, retinitis pigmentosa (RP) patients suffer from night blindness which causes nocturnal mobility difficulties. We created a wearable visual aid that uses a high-performance see-through display, and added a high-sensitivity camera with a complementary metal-oxide-semiconductor sensor. Here, we evaluate the device's efficacy for helping night-blindness sufferers walk in the dark. STUDY DESIGN: Prospective clinical study. METHODS: Twenty-eight subjects underwent binocular visual acuity testing in the dark without (power off) and with (power on) the device. The test was carried out in a darkened room. We recorded the number of trial errors and the time it took each subject to arrive at the goal both with and without the aid of our device. RESULTS: Our device effectively assists walking in RP patients with mobility problems in the dark. CONCLUSION: Binocular visual acuity in the dark was significantly improved with the aid of our device. In the walking test, the number of errors decreased greatly with the device, and the travel time was significantly shortened.

Vitamin A deficiency is associated with body mass index and body adiposity in women with recommended intake of vitamin A.

INTRODUCTION: evidence indicates that vitamin A is involved in regulating fat mass. A low consumption of vitamin A has been reported in individuals with obesity, as have lower concentrations of this vitamin, than in eutrophic individuals when their dietary intake of vitamin A is not significantly different. OBJECTIVE: to investigate vitamin A nutritional status and its association with body mass index (BMI) and body fat in women who have the recommended dietary intake of vitamin A. METHODS: cross-sectional study with 200 women, paired by age and by the dietary intake of vitamin A recommended. Participants were divided into four groups, according to BMI. Anthropometric data were evaluated (weight, BMI and waist circumference [WC]), as well as the diagnosis of night blindness (NB). Lipid and glycemic profiles were measured. The cut-off points for deficiency of serum concentrations of retinol and ß-carotene were < 1.05 µmol/l and 40 µg/dl, respectively. The recommended dietary intake of vitamin A was 700 µg/day. RESULTS: there was a significant drop in retinol concentrations according to BMI (p < 0.001) and WC (p < 0.001). We found ß-carotene to behave similarly (p = 0.005; p < 0.001). We found NB in 7.5% of overweight (OW) cases and 20.0% of obesity class II (OII), and no functional alteration was found in the eutrophic group (EU). Inadequate levels of retinol and ß-carotene increased the odds ratio for the occurrence of OW, obesity class I (OI) and OII, as well as inadequate WC. CONCLUSION: even with recommended intake of vitamin A, we found a biochemical and functional inadequacy of vitamin A nutritional status,associated with overweight, obesity and body adiposity.

Vitamin A deficiency is associated with body mass index and body adiposity in women with recommended intake of vitamin A / La deficiencia de vitamina A se asocia con el índice de masa corporal y la adiposidad corporal en mujeres con ingesta recomendada de vitamina A

Introduction: evidence indicates that vitamin A is involved in regulating fat mass. A low consumption of vitamin A has been reported in individuals with obesity, as have lower concentrations of this vitamin, than in eutrophic individuals when their dietary intake of vitamin A is not significantly different. Objective: to investigate vitamin A nutritional status and its association with body mass index (BMI) and body fat in women who have the recommended dietary intake of vitamin A. Methods: cross-sectional study with 200 women, paired by age and by the dietary intake of vitamin A recommended. Participants were divided into four groups, according to BMI. Anthropometric data were evaluated (weight, BMI and waist circumference [WC]), as well as the diagnosis of night blindness (NB). Lipid and glycemic profiles were measured. The cut-off points for deficiency of serum concentrations of retinol and β-carotene were < 1.05 μmol/l and 40 μg/dl, respectively. The recommended dietary intake of vitamin A was 700 μg/day. Results: there was a significant drop in retinol concentrations according to BMI (p < 0.001) and WC (p < 0.001). We found β-carotene to behave similarly (p = 0.005; p < 0.001). We found NB in 7.5% of overweight (OW) cases and 20.0% of obesity class II (OII), and no functional alteration was found in the eutrophic group (EU). Inadequate levels of retinol and β-carotene increased the odds ratio for the occurrence of OW, obesity class I (OI) and OII, as well as inadequate WC. Conclusion: even with recommended intake of vitamin A, we found a biochemical and functional inadequacy of vitamin A nutritional status, associated with overweight, obesity and body adiposity

Introducción: la evidencia indica que la vitamina A esta involucrada en la regulación de la masa grasa. Un bajo consumo de vitamina A ha sido reportado en individuos con obesidad, ya que tienen concentraciones mas bajas de esta vitamina que los individuos eutróficos a pesar de que su ingesta dietética de vitamina A no es significativamente diferente. Objetivo: investigar el estado nutricional de la vitamina A y su asociación con el índice de masa corporal (IMC) y la grasa corporal en las mujeres que tienen la ingesta dietética recomendada de vitamina A. Métodos: estudio transversal con 200 mujeres, emparejado por edad y por la ingesta dietética de vitamina A recomendada. Se dividieron en cuatro grupos, de acuerdo con el IMC. Los datos antropométricos fueron evaluados (peso, índice de masa corporal [IMC] y circunferencia de la cintura [CC]), así como el diagnostico de ceguera nocturna (CN). Se midieron los perfiles lipídicos y glicémicos. Los puntos de corte para la deficiencia de las concentraciones séricas de retinol y β-caroteno fueron < 1,05 μmol/l y 40 μg/dl, respectivamente. La ingesta dietética recomendada de vitamina A fue de 700 μg/día. Resultados: hubo una disminución significativa de las concentraciones de retinol según el IMC (p < 0,001) y CC (p < 0,001). Se observo un comportamiento similar del β-caroteno (p = 0,005, p < 0,001). Encontramos NB en el 7,5% de los casos con sobrepeso (OW) y el 20,0% de los casos con obesidad clase II (OII), y no encontramos alteración funcional en la UE. Niveles inadecuados de retinol y (R)-caroteno aumentaron la odds ratio para la ocurrencia de OW, obesidad clase I (OI) y OII, al igual que los niveles insuficientes de CC. Conclusión: incluso con la ingesta recomendada de vitamina A, encontramos una deficiencia bioquímica y funcional del estado nutricional de vitamina A asociada al sobrepeso, la obesidad y la adiposidad corporal