Exfoliation syndrome: assembling the puzzle pieces

Abstract

ABSTRACT.Purpose: To summarize various topics and the cutting edge approaches to refine XFS pathogenesis that were discussed at the 21st annual Glaucoma Foundation Think Tank meeting in New York City, Sept. 19-20, 2014. Methods: The highlights of three categories of talks on cutting edge research in the field were summarized. Results: Exfoliation syndrome (XFS) is a systemic disorder with a substantial ocular burden, including high rates of cataract, cataract surgery complications, glaucoma and retinal vein occlusion. New information about XFS is akin to puzzle pieces that do not quite join together to reveal a clear picture regarding how exfoliation material (XFM) forms. Conclusion: Meeting participants concluded that it is unclear how the mild homocysteinemia seen in XFS might contribute to the disarrayed extracellular aggregates characteristic of this syndrome. Lysyl oxidase-like 1 (LOXL1) variants are unequivocally genetic risk factors for XFS but exactly how these variants contribute to the assembly of exfoliation material (XFM) remains unclear. Variants in a new genomic region, CACNA1A associated with XFS, may alter calcium concentrations at the cell surface and facilitate XFM formation but much more work is needed before we can place this new finding in proper context. It is hoped that various animal model and ex vivo systems will emerge that will allow for proper assembly of the puzzle pieces into a coherent picture of XFS pathogenesis. A clear understanding of XFS pathogenesis may lead to 'upstream solutions' to reduce the ocular morbidity produced by XFS.

Nailfold capillary morphology in exfoliation syndrome

“…Number of hemorrhages per 100 capillaries 0.0 and plasma compared with controls. 17,40 Serum Hcy may also be elevated in XFS/XFG compared with POAG, [41][42][43] although this remains controversial. 44,45 Hcy is a nonproteinogenic amino acid that is an intermediate molecule generated during the conversion of methionine to cysteine.…”

“…15 Fingertip cutaneous capillary blood flow measured by laser Doppler flowmetry is lower in XFG compared with POAG and controls and the duration of cold-induced blood flow reduction as well as recovery periods are longer in XFG compared with POAG and controls. 16 However, reports of systemic vascular comorbidities in XFS/ XFG remain inconsistent 17,18 and further study is necessary to describe vascular changes in XFS/XFG. Nailfold capillary videomicroscopy allows convenient in vivo visualization of the microvasculature at the junction of the fingernail and skin.…”

The Incidence of Retinal Vein Occlusion in Patients with Pseudoexfoliation Glaucoma: A Retrospective Cohort Study

“…Of note, the different populations in our study compared to the study by Jonas et al may possibly point to a different genetic as well as environmental predisposition to RVO in our PXF group. Supporting this supposition, a recent study by Pasquale et al [12] emphasized that environmental and genetic factors have an effect on PXF.…”

Genetics, Diagnosis, and Monitoring of Pseudoexfoliation Glaucoma

“…Elevated plasma and aqueous homocysteine has been observed in pseudoexfoliation patients in a number of studies (6). It is unclear whether homocysteine plays a causative role in pseudoexfoliation, with one proposed mechanism by Pasquale et al being the disruption of disulfide bonds of cysteine residues in extracellular matrix proteins (6).…”