A case report of retinal dystrophy in patients with PACS1 syndrome.

PACS1 syndrome, also referred to as Schuurs-Hoeijmakers syndrome, is a multisystemic developmental disorder caused by a specific pathogenic variant in the PACS1 (phosphofurin acidic cluster sorting protein 1) gene. Ocular findings in PACS1 syndrome are known to include iris, retina, optic nerve coloboma, myopia, nystagmus, and strabismus. Here, we present the cases of two patients referred to the University of Wisconsin-Madison Department of Ophthalmology and Visual Sciences for ocular evaluation. The first patient is a 14-month-old female who, at 3 months of age, was found to have a depressed rod and cone response on electroretinogram (ERG), consistent with possible retinal dystrophy (RD). This feature has not been previously described in PACS1 syndrome and joins a growing list of calls for expanding the PACS1 phenotype. The second case illustrates a 5-year-old male referred for ocular screening after diagnosing PACS1 syndrome and underwent ERG without abnormal findings. These cases demonstrate the significant variability in the ophthalmic presentation of PACS1 syndrome and the need for early screening. These novel findings may have implications in understanding the mechanism of the PACS1 protein and its role in retinal ciliary phototransduction in photoreceptors.

MFRP variant results in nanophthalmos, retinitis pigmentosa, variability in foveal avascular zone.

BACKGROUND: Membrane frizzled-related protein (MFRP) plays a critical role in ocular development. MFRP mutations are known to cause nanophthalmos and, in some cases, retinitis pigmentosa, foveoschisis, and/or optic nerve head (ONH) drusen. The broad clinical spectrum of MFRP mutations necessitates further investigation of specific genotype-phenotype relationships. MATERIALS AND METHODS: We reviewed ophthalmologic and genetic medical records of two affected siblings and one unaffected sibling. RESULTS: Genetic testing revealed variants MFRP c.855T>A, p.(Cys285*) and MFRP c.1235T>C, p.(Leu412Pro) in trans in the two affected siblings. In both cases, photopic and scotopic responses were markedly reduced on electroretinogram (ERG), with greater decrease in scotopic function. Optical coherence tomography for both siblings revealed non-cystoid thickening. Blunted foveal reflexes were also observed in both siblings. Notably, foveal avascular zone abnormalities were seen on fundus autofluorescence in only one affected sibling. CONCLUSIONS: MFRP-related ocular disease may be underrecognized due to its presentation with high hyperopia and possibly subtle retinal findings. Presence of variants MFRP c.855T>A, p.(Cys285*) and MFRP c.1235T>C, p.(Leu412Pro) in trans resulted in nanophthalmos and retinitis pigmentosa without associated foveoschisis or ONH drusen in our patients, consistent with the incomplete phenotype previously described in Neri et al. Abnormalities in the foveal avascular zone have been noted in other case studies and were inconsistently associated with the variants described here, representing a potential area for future investigation.

Impact of Amblyopia on the Central Nervous System.

Amblyopia is a common perceptual disorder resulting from abnormal visual input during development. The clinical presentation and visual deficits associated with amblyopia are well characterized. Less is known however, about amblyopia's impact on the central nervous system (CNS). While early insights into the neuropathophysiology of amblyopia have been based on findings from animal models and postmortem human studies, recent advances in noninvasive magnetic resonance imaging (MRI) techniques have enabled the study of amblyopia's effects in vivo. We review recent retinal and neuroimaging research documenting amblyopia's structural and functional impact on the CNS. Clinical imaging provides some evidence for retinal and optic nerve abnormalities in amblyopic eyes, although the overall picture remains inconclusive. Neuroimaging studies report clearer changes in both structure and function of the visual pathways. In the optic nerves, optic tracts, and optic radiations of individuals with amblyopia, white-matter integrity is decreased. In the lateral geniculate nuclei, gray matter volume is decreased and neural activity is reduced. Reduced responses are also seen in the amblyopic primary visual cortex and extrastriate areas. Overall, amblyopia impacts structure and function at multiple sites along the visual processing hierarchy. Moreover, there is some evidence that amblyopia's impact on the CNS depends on its etiology, with different patterns of results for strabismic and anisometropic amblyopia. To clarify the impact of amblyopia on the CNS, simultaneous collection of retinal, neural, and perceptual measures should be employed. Such an approach will help (1) distinguish cause and effect of amblyopic impairments, (2) separate the impact of amblyopia from other superimposed conditions, and (3) identify the importance of amblyopic etiology to specific neural and perceptual deficits.

Risk Factors for Intracardiac Thrombus During Liver Transplantation.

Intracardiac thrombus (ICT) is an intraoperative complication with high mortality that occurs during orthotopic liver transplantation (OLT). Patients with end-stage liver disease have compromised coagulation pathways, and when combined with stressors of surgery, thrombi can form. However, it is unknown which patients are most likely to develop ICT. We performed a retrospective cohort study of all OLT patients at our hospital from 2010 to 2017 to identify risk factors for ICT. An analysis was performed with conventional bivariate tests and logistic regression. The incidence of ICT during OLT was 4.2% (22/528) with a 45.5% (10/22) mortality. Patients who developed ICT had higher physiologic Model for End-Stage Liver Disease scores at the time of transplant (25.1 versus 32.4; P = 0.004), received grafts from donors with a higher body mass index (28.1 versus 32.2 kg/m2 ; P = 0.007), and had longer intraoperative warm ischemia times (53.1 versus 67.5 minutes; P = 0.001). The odds of developing ICT were significantly lower after administration of intravenous (IV) heparin prior to inferior vena cava (IVC) clamping compared with no administration of heparin (odds ratio, 0.25; 95% confidence interval, 0.08-0.75; P = 0.01). In conclusion, the incidence of ICT at our institution is higher than previously reported, which may be explained by our routine use of transesophageal echocardiography. Although many factors associated with ICT in this study are nonmodifiable, administration of IV heparin prior to IVC cross-clamping is modifiable and was found to be protective. Further studies will be needed to confirm findings and ultimately aid in preventing these lethal events.