Ocular morphology and function in juvenile neuronal ceroid lipofuscinosis (CLN3) in the first decade of life.

PURPOSE: CLN3 is a rare lysosomal storage disorder. The majority of the patients suffer from neurological degeneration in the first decade of life leading to death in the second or third decade. One of the first symptoms is a rapid visual decline from retinal degeneration. The aim of this study was to correlate the retinal changes in CLN3 as seen with spectral domain optical coherence tomography (SD-OCT) with functional data in patients in the first years after the subjective onset of ocular symptoms. METHODS: Three unrelated children aged from 5.6 to 8.8 years, and with molecularly confirmed CLN3, underwent a comprehensive ophthalmological examination including visual acuity, fundus photography, fundus autofluorescence (FAF), electrophysiology (multifocal ERG), Goldmann visual fields, and SD-OCT. RESULTS: A predominant loss of the first and second neuron retinal layers progressing from the macula to the periphery was identifed. The retinal nerve fibre layer (RNFL) displayed gliosis and an irregular lining of the inner limiting membrane. Compared to the preferential reduction of photoreceptor layer thickness in other maculopathies with pan-retinal involvement, the thickness of the first and second neuron layers was reduced simultaneously in CLN3. Functional testing by multifocal ERG reflected the degenerative progress. Semiquantitative evaluation revealed a generally reduced FAF. CONCLUSION: This is the first detailed morphological evaluation of CLN3 patients in the first years after the subjective onset of ocular symptoms. CLN3 is characterized by an early degeneration predominant of the first and second neuron compared to other macular and generalized retinal dystrophies. Imaging is instrumental for early diagnosis and gene-directed molecular analysis of this fatal disorder.

In-line filtration minimizes organ dysfunction: new aspects from a prospective, randomized, controlled trial.

BACKGROUND: Infused particles induce thrombogenesis, impair microcirculation and modulate immune response. We have previously shown in critically ill children, that particle-retentive in-line filtration reduced the overall complication rate of severe events, length of stay and duration of mechanical ventilation. We now evaluated the influence of in-line filtration on different organ function and thereby elucidated the potential underlying pathophysiological effects of particle infusion. METHODS: In this single-centre, prospective, randomized controlled trial 807 critically ill children were assigned to either control (n = 406) or filter group (n = 401), the latter receiving in-line filtration for complete infusion therapy. Both groups were compared regarding the differences of incidence rates and its 95% confidence interval (CI) of different organ dysfunction as defined by the International Pediatric Sepsis Consensus Conference 2005. RESULTS: The incidence rates of respiratory (-5.06%; 95% CI, -9.52 to -0.59%), renal (-3.87%; 95% CI, -7.58 to -0.15%) and hematologic (-3.89%; 95% CI, -7.26 to -0.51%) dysfunction were decreased in the filter group. No difference was demonstrated for the occurrence rates of cardiovascular, hepatic, or neurologic dysfunction between both groups. CONCLUSIONS: In-line filtration has beneficial effects on the preservation of hematologic, renal and respiratory function in critically ill patients. The presented clinical data further support our hypothesis regarding potential harmful effects of particles. In critically ill patients infused particles may lead to further deterioration of the microcirculation, induce a systemic hypercoagulability and inflammation with consecutive negative effects on organ function. TRIAL REGISTRATION: ClinicalTrials.gov number; NCT00209768.