Leberjeva hereditarna optična nevropatija – pregled bolezni z analizo prisotnosti v Sloveniji

Leberjeva hereditarna optična nevropatija (LHON) je redka dedna mitohondrijska bolezen, ki povzroča slepoto najpogosteje pri mladih odraslih. Navadno se izrazi kot subakutna, neboleča izguba vida na eno oko, ki ji sledi poslabšanje vida drugega očesa v nekaj tednih do mesecih. Bolezen večinoma pušča trajne posledice, le pri nekaterih bolnikih lahko v redkih primerih pride do delnega spontanega izboljšanja vida. Razmerje med moškimi in ženskimi bolniki se ocenjuje na 3 : 1. V zadnjih letih je z razvojem zdravilne učinkovine idebenone možno podporno farmakološko zdravljenje, ki lahko prispeva k delnemu izboljšanju vidne funkcije. Bolezen zaradi svoje redkosti velikokrat ostane ne- ali napačno diagnosticirana. V članku predstavljamo štiri klinične primere bolnikov, pri katerih se je po obsežnem in dolgotrajnem diagnosticiranju izkazalo, da imajo LHON. Od leta 1996 se v Sloveniji vodi baza bolnikov z redkimi dednimi očesnimi boleznimi. Na tej podlagi je ocenjena prevalenca LHON 1/72.000. Ob sumu na bolezen so ključni družinska anamneza slabovidnosti po materini strani, genetsko testiranje in napotitev na obravnavo ter zdravljenje v terciarno ustanovo

Rezultati dela Ambulante za bolezni dojk pri Splošni bolnišnici Trbovlje

V članku avtorji prikazujejo rezultate dela Ambulante za bolezni dojk pri ginekološko-porodniškem oddelku Splošne bolnišnice Trbovlje. V devetih letih dela ambulante za bolezni dojk so opravili več kot 10.000 pregledov. Na dodatne preglede so napotili 171 pregledanih žensk. Pri 78 (47 %) napotenih ženskah je bil potrjen rak dojke. Pri 15 (19,2 %) je bil rak dojke v začetnem, neinvazivnem stadiju, pri 63 (80,7 %) pa v invazivnem stadiju bolezni. Pri 24 (30,7 %) so bile metastaze že v regionalnih bezgavkah, pri 48 (61,54 %) bolnicah pa takih metastaz niso ugotovili. Za 5 (6,4 %) bolnic ni podatkov, ugotovili so en primer vnetnega raka. Ugotavljajo 9 intervalnih rakov, kar je 0,09 % od vseh pregledanih žensk oz. 11,3 % ugotovljenih rakov. Ugotavljajo, da je v prikazanem vzorcu rak dojke zelo pogost že pred 50. letom starosti28,2 % primerov je bilo v starostni skupini 30–49 let, v skupini 50–69 let pa 47,4 % vseh za rakom na dojki obolelih žensk. To pomeni, da je v starostni skupini 30–69 let za rakom dojke zbolelo 75,6 % vseh obolelih. Ugotavljajo tudi pomanjkljivo povezavo med družinskimi zdravniki, Onkološkim inštitutom in ambulanto za bolezni dojk

Aspectos gerais e número de etapas do sistema de medicação de quatro hospitais brasileiros

This study identified and analyzed the medication systems in 04 university hospitals located in Recife, Ribeirão Preto, Goiânia and São Paulo, Brazil, after approval by the Research Ethics Committee and authorization by the hospital directors. Data were collected through a structured interview with one of the professionals in charge of the medication system and non-participant and direct observation during one week. The results indicated the points requiring improvement, such as the use of abbreviations, lack of standardization in medication administration times, lack of updated and complete information about the patient, the pharmacy's not working 24 hours a day in hospitals and others. 66 phases were shown in Hospital A, 58 in B, 70 in C, and 80 in D concerning the medication system. Simplifying the processes by reducing the number of phases is the key to reducing medication errors.Esa investigación identificó y analizó el sistema de medicación en 04 hospitales universitarios en las ciudades de Recife, Ribeirão Preto, Goiânia y São Paulo, Brasil. Los datos fueron recopilados en dos etapas. En la primera etapa se realizó una entrevista estructurada con uno de los profesionales responsables por el sistema de medicación. En la segunda, se hizo observación no participativa y directa durante una semana. Los resultados indicaron los puntos que necesitan ser perfeccionados, tales como uso de abreviaciones, la falta de un padrón de horarios, falta de información actualizada y completa del paciente, farmacia que no funciona las 24 horas en un hospital, y otros. Se observó en el Hospital A 66 etapas, en el B 58 etapas, en el C 70 etapas y en el D 80 etapas respecto al sistema de medicación. Simplificar el proceso, diminuyendo el número de etapas, es la clave para reducir los márgenes de errores en la medicación.Essa investigação identificou e analisou o sistema de medicação de 04 hospitais universitários, localizados nas cidades de Recife, Ribeirão Preto, Goiânia e São Paulo, após a aprovação nos Comitês de Ética em Pesquisa e da autorização da direção dos hospitais. Os dados foram coletados através de entrevista estruturada com um dos profissionais responsáveis pelo sistema de medicação e observação não participante e direta, por uma semana, nos vários sub-sistemas. Os resultados indicaram pontos que necessitam de aperfeiçoamentos como utilização de abreviações, falta de padronização de horários de administração de medicamentos, falta de informações atualizadas e completas do paciente, farmácia não funcionando 24 horas em um hospital, falta de centro de informações de medicamentos e outros. Evidenciou-se no hospital A 66 etapas, no B 58 etapas, no C 70 etapas e no D 80 etapas do sistema de medicação. Simplificar os processos, diminuindo o número de etapas, é a chave para a redução de erros de medicação

Electroretinography as a Biomarker to Monitor the Progression of Stargardt Disease

The aim of the present study is to determine how electroretinographic (ERG) responses reflect age-related disease progression in the Stargardt disease (STGD1). The prospective comparative cohort study included 8 patients harboring two null ABCA4 variants (Group 1) and 34 patients with other ABCA4 genotypes (Group 2). Age at exam, age at onset, visual acuity (VA) and ERG responses were evaluated. The correlation between ERG responses and age in each patient group was determined using linear regression. A Mann-Whitney U Test was used to compare the median values between the groups. Age of onset was significantly earlier in Group 1 than in Group 2 (8 vs. 18), while disease duration was similar (13 vs. 12 years, i.e., advanced stage). Group 1 had significantly worse VA and lower ERG responses. ERG responses that significantly correlated with age in Group 1 were DA 0.01 and 3.0 ERG, which represented a retinal rod system response. The only ERG response that significantly correlated with age in Group 2 was the S-cone ERG. The observed difference was likely due to early cone loss occurring in double-null patients and slower photoreceptor loss in patients with other genotypes. The results suggest that specific ERG responses may be used to detect double-null patients at an early stage and monitor STGD1 disease progression in patients with specific genotypes

The role of vitamin A in retinal diseases

Vitamin A is an essential fat-soluble vitamin that occurs in various chemical forms. It is essential for several physiological processes. Either hyper- or hypovitaminosis can be harmful. One of the most important vitamin A functions is its involvement in visual phototransduction, where it serves as the crucial part of photopigment, the first molecule in the process of transforming photons of light into electrical signals. In this process, large quantities of vitamin A in the form of 11-cis-retinal are being isomerized to all-trans-retinal and then quickly recycled back to 11-cis-retinal. Complex machinery of transporters and enzymes is involved in this process (i.e., the visual cycle). Any fault in the machinery may not only reduce the efficiency of visual detection but also cause the accumulation of toxic chemicals in the retina. This review provides a comprehensive overview of diseases that are directly or indirectly connected with vitamin A pathways in the retina. It includes the pathophysiological background and clinical presentation of each disease and summarizes the already existing therapeutic and prospective interventions

Fundus autofluorescence and optical coherence tomography in relation to visual function in Usher syndrome type 1 and 2

Purpose of this study was to characterize retinal disease in Usher syndrome using fundus autofluorescence and optical coherence tomography. Study included 54 patients (26 male, 28 female) aged 7–70 years. There were 18 (33%) USH1 and 36 (67%) USH2 patients. 49/52 (94%) patients were found to carry at least one mutation in Usher genes. Ophthalmological examination included assessment of Snellen visual acuity, color vision with Ishihara tables, Goldmann visual fields (targets II/1–4 and V/4), microperimetry, fundus autofluorescence imaging and optical coherence tomography. Average age at disease onset (nyctalopia) was significantly lower in USH1 than USH2 patients (average 9 vs. 17 years, respectively; p < 0.01); however no significant differences were found regarding type of autofluorescence patterns, frequency of foveal lesions and CME, rate of disease progression and age at legal blindness. All representative eyes had abnormal fundus autofluorescence of either hyperautofluorescent ring (55%), hyperautofluorescent foveal patch (35%) or foveal atrophy (10%). Disease duration of more than 30 years was associated with a high incidence of abnormal central fundus autofluorescence (patch or atrophy) and visual acuity loss

Correlation between the Serum Concentration of Vitamin A and Disease Severity in Patients Carrying p.G90D in <i>RHO</i>, the Most Frequent Gene Associated with Dominant Retinitis Pigmentosa: Implications for Therapy with Vitamin A

The pathogenic variant p.G90D in RHO is believed to be responsible for a spectrum of phenotypes, including congenital stationary blindness (for the purpose of this study termed night blindness without degeneration; NBWD), Sector RP, Pericentral RP, and Classic RP. We present a correlation between the serum concentration of vitamin A and disease severity in patients with this variant. This prospective study involved 30 patients from 7 families (17 male; median age 46 years, range 8–73). Full ophthalmological examination including visual acuity, Goldmann perimetry, slit-lamp exam, optical coherence tomography, fundus autofluorescence, and electrophysiology was performed to determine the presenting phenotype. The serum concentration of vitamin A was determined from a fasting blood sample taken on the day of the exam, where it was found that 23.3% (7/30) of patients had NBWD, 13.3% (4/30) had Sector RP, 3.3% (1/30) had Pericentral RP, and 60% (18/30) had Classic RP. Multiple logistic regression revealed a significantly higher probability of having a milder phenotype (NBWD or Sector RP) in association with younger age (p p cis-retinal form plays a role in stabilizing the constitutively active p.G90D rhodopsin and its supplementation could be a potential treatment strategy for p.G90D RHO patients

Stargardt-like Clinical Characteristics and Disease Course Associated with Variants in the <i>WDR19</i> Gene

Variants in WDR19 (IFT144) have been implicated as another possible cause of Stargardt disease. The purpose of this study was to compare longitudinal multimodal imaging of a WDR19-Stargardt patient, harboring p.(Ser485Ile) and a novel c.(3183+1_3184-1)_(3261+1_3262-1)del variant, with 43 ABCA4-Stargardt patients. Age at onset, visual acuity, Ishihara color vision, color fundus, fundus autofluorescence (FAF), spectral-domain optical coherence tomography (OCT) images, microperimetry and electroretinography (ERG) were evaluated. First symptom of WDR19 patient was nyctalopia at the age of 5 years. After the age of 18 years, OCT showed hyper-reflectivity at the level of the external limiting membrane/outer nuclear layer. There was abnormal cone and rod photoreceptor function on ERG. Widespread fundus flecks appeared, followed by perifoveal photoreceptor atrophy. Fovea and peripapillary retina remained preserved until the latest exam at 25 years of age. ABCA4 patients had median age of onset at 16 (range 5–60) years and mostly displayed typical Stargardt triad. A total of 19% had foveal sparing. In comparison to ABCA4 patients, the WDR19 patient had a relatively large foveal preservation and severe rod photoreceptor impairment; however, it was still within the ABCA4 disease spectrum. Addition of WDR19 in the group of genes producing phenocopies of Stargardt disease underlines the importance of genetic testing and may help to understand its pathogenesis

The Clinical Spectrum and Disease Course of DRAM2 Retinopathy

Pathogenic variants in DNA-damage regulated autophagy modulator 2 gene (DRAM2) cause a rare autosomal recessive retinal dystrophy and its disease course is not well understood. We present two Slovenian patients harboring a novel DRAM2 variant and a detailed review of all 23 other patients described to date. Whole exome and whole genome sequencing were performed in the two patients, and both underwent ophthalmological examination with a 2-year follow-up. PubMed was searched for papers with clinical descriptions of DRAM2 retinopathy. Patient 1 was homozygous for a novel variant, p.Met1?, and presented with the acute onset of photopsia and retina-wide retinopathy at the age of 35 years. The patient was first thought to have an autoimmune retinopathy and was treated with mycophenolate mofetil, which provided some symptomatic relief. Patient 2 was compound heterozygous for p.Met1? and p.Leu246Pro and presented with late-onset maculopathy at the age of 59 years. On review, patients with DRAM2 retinopathy usually present in the third decade with central visual loss, outer retinal layer loss on optical coherence tomography and a hyperautofluorescent ring on fundus autofluorescence. Either cone–rod or rod–cone dystrophy phenotype is observed on electroretinography, reflecting the importance of DRAM2 in both photoreceptor types. Non-null variants can result in milder disease