Ophthalmological findings in Gaucher disease

Eghbali, Areian; Hassan, Shahzeb; Seehra, Gurpreet; FitzGibbon, Edmond J.; Sidransky, Ellen

doi:10.1016/j.ymgme.2019.02.002

Cited by 11 publications

(9 citation statements)

References 39 publications

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“…Pathological abnormalities and vision dysfunction have been detected in patients with PD and GD, and in other lysosomal storage disorders, including Dannon disease, Fabry disease, and mucopolysaccharidoses 10,[12][13][14][15]22,[41][42][43] . Specifically, glaucoma has been reported for PD and mucopolysaccharidoses 15,41,42 .…”

Section: Discussionmentioning

confidence: 99%

Ocular phenotypes in a mouse model of impaired glucocerebrosidase activity

Weber¹,

Min²,

Truong³

et al. 2021

Sci Rep

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Mutations in the GBA1 gene encoding glucocerebrosidase (GCase) are linked to Gaucher (GD) and Parkinson’s Disease (PD). Since some GD and PD patients develop ocular phenotypes, we determined whether ocular phenotypes might result from impaired GCase activity and the corresponding accumulation of glucosylceramide (GluCer) and glucosylsphingosine (GluSph) in the Gba1D409V/D409V knock-in (Gba KI/KI; “KI”) mouse. Gba KI mice developed age-dependent pupil dilation deficits to an anti-muscarinic agent; histologically, the iris covered the anterior part of the lens with adhesions between the iris and the anterior surface of the lens (posterior synechia). This may prevent pupil dilation in general, beyond an un-responsiveness of the iris to anti-muscarinics. Gba KI mice displayed atrophy and pigment dispersion of the iris, and occlusion of the iridocorneal angle by pigment-laden cells, reminiscent of secondary open angle glaucoma. Gba KI mice showed progressive thinning of the retina consistent with retinal degeneration. GluSph levels were increased in the anterior and posterior segments of the eye, suggesting that accumulation of lipids in the eye may contribute to degeneration in this compartment. We conclude that the Gba KI model provides robust and reproducible eye phenotypes which may be used to test for efficacy and establish biomarkers for GBA1-related therapies.

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Section: Discussionmentioning

confidence: 99%

Ocular phenotypes in a mouse model of impaired glucocerebrosidase activity

Weber¹,

Min²,

Truong³

et al. 2021

Sci Rep

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“…Gaucher disease (GD; MIM# 230,800, 230,900, 231,000, 231,005) is a rare inherited lysosomal storage disorder that primarily affects the reticuloendothelial lineage. Mutations in the GBA1 gene lead to deficiency in the lysosomal enzyme β‐glucocerebrosidase (GCase), resulting in accumulation of glucocerebroside in cells, particularly macrophages 1 …”

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confidence: 99%

Ganglion Cell Complex Thinning in Young Gaucher Patients: Relation to Prodromal Parkinsonian Markers

et al. 2020

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A BS TRACT: Background: Patients with Gaucher disease (GD) have an increased risk for parkinsonism. Retinal thinning has been described in parkinsonism as an early nonmotor feature. Scarce reports have addressed retinal thickness changes in GD. Objectives: The objectives of this study were to compare ganglion cell complex (GCC) thickness in adolescents and young adults (AYAs) with GD with healthy control subjects, and to correlate it with the presence of parkinsonian features (PFs), clinical prodromal markers of parkinsonism, severity score index (SSI), and glucosylsphingosine (Lyso-GL-1). Methods: This study included 48 AYAs with GD (11-29 years), 11 with manifest PFs (Group 1) and 37 with no PFs (Group 2), and 48 matched healthy control subjects (Group 3). Age of GD onset, disease duration, medication history, history of constipation, SSI, and hematological assessment were done. Neurocognitive evaluation included Parts I, II, and III of the Unified Parkinson's Disease Rating Scale (UPDRS), Wechsler Adult and Intelligence Scale and Wechsler Intelligence Scale for Children, Beck Depression Inventory (BDI), rapid eye movement sleep behavior disorder (RBD) scale, Munich Parasomnia Screening scale, and the olfactory dysfunction scale. Molecular analyses of the acid GBA gene and Lyso-GL-1 were done. Participants underwent full ophthalmological examination and optical coherence tomography with GCC thickness measurement. Results: GCC was significantly thinner in Group 1 than in Groups 2 and 3 (P < 0.001), whereas no significant difference was found between Groups 2 and 3 (P = 0.977). In addition, a significant interocular GCC thickness difference was found among the studied AYAs with GD (P = 0.007). GCC correlated positively with total intelligence quotient (P < 0.001) and negatively with Lyso-GL-1 (P = 0.019), UPDRS (P = 0.004), and BDI (P = 0.029), but not with SSI (P = 0.874), GD type (P = 0.85), or genotype (P = 0.842). A significant negative relationship was found between GCC thickness and PFs (P = 0.001), parasomnia (P = 0.003), constipation (P = 0.031), RBD (P = 0.044), and hyposmia (P = 0.033). Conclusions: GCC thinning may be a promising biomarker for central nervous system neurodegeneration that has the potential to monitor early PFs among people with GD.

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“…It has previously been reported that patients with GD can develop a variety of ocular findings (Eghbali et al, ; Winter et al, ). This case series focused on the development of white vitreous opacities in light of other clinical findings in five patients with GD3.…”

Section: Discussionmentioning

confidence: 99%

“…It has previously been reported that patients with GD can develop a variety of ocular findings (Eghbali et al, 2019;Winter et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

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White vitreous opacities in five patients with Gaucher disease type 3

Seehra

Eghbali

Sidransky

et al. 2020

American J of Med Genetics Pt A

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Fundal abnormalities, including preretinal and retinal changes, are a rare finding in patients with the autosomal recessive lysosomal storage disorder Gaucher disease, most often described in patients with the chronic neuronopathic form (type 3). We evaluated whether these ophthalmological findings correlated with other manifestations of type 3 Gaucher disease. Reviewing the records of 40 patients with type 3 Gaucher disease, we identified five with white vitreous opacities and reviewed their clinical course in depth. Each of the patients described decreased visual acuity and “floaters” obstructing their vision. The development and/or progression of these fluffy‐appearing white opacities in each patient were tracked longitudinally in the context of their neurological and other clinical findings. It was noted that all five patients shared genotype p.L483P/p.L483P (L444P/L444P) and had significant neurological, oculomotor and bone involvement and two had undergone splenectomy. Enzyme replacement therapy with recombinant glucocerebrosidase did not prevent the development or progression of these ocular opacities. Since preretinal findings, in addition to other neuro‐ophthalmological findings, can be a feature of Gaucher disease, it is recommended that patients be monitored by regular eye examinations.

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Ophthalmological findings in Gaucher disease

Cited by 11 publications

References 39 publications

Ocular phenotypes in a mouse model of impaired glucocerebrosidase activity

Ocular phenotypes in a mouse model of impaired glucocerebrosidase activity

Ganglion Cell Complex Thinning in Young Gaucher Patients: Relation to Prodromal Parkinsonian Markers

White vitreous opacities in five patients with Gaucher disease type 3

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