Education Committee Highlights WGC-2021 | part 2.2

Pseudo-exfoliation – latest updates

Exfoliation Glaucoma: How to diagnose and treat?
At the beginning Dr. Gabor Hollo described the physiopathology of the exfoliation. He also showed some example of different clinical presentation. He introduced the genetic aspects of the disease: common sequence variants in the LOXL1 gene confer susceptibility to exfoliation syndrome.

Changes in aqueous humour in Exfoliation Glaucoma is also presented. Increased TGFB1, decreased MMP2 and other oxidative stress parameters were found.

Several diagnostic problems in exfoliation syndrome may be detected: poorly dilating pupil, single IOP measurement instead of diurnal IOP curve, early forms of exfoliation syndrome are not recognized and lastly exfoliation syndrome cannot diagnose with genetic test.

He reviewed the treatment for glaucoma syndrome. Medical, laser therapy and also surgery possibilities (MMC trabeculectomy as the gold standard). In conclusion, exfoliation glaucoma is still a challenging disease.

Genetics of PXF
Prof. Chiea Chuen Khor introduced the definition of exfoliation syndrome. He presented some genetics aspects of the syndrome. They changed the approach trying to find a better association between different genes involved and the syndrome and then he cited his study using evaluation of proteins. Briefly, they applied exome sequencing to study exfoliation syndrome. When they analyzed the results, they found that the LOXL1 and CYP39A1 (new gene) have a high risk of developing the syndrome. Later, in a metanalysis they also found that patients who carry mutation in the CYP39A1 have more chance to have exfoliation syndrome.

Finally, they should how in the future doctors may look the for-glaucoma genetics. Artificial intelligence may use this to calculate the increased risk to develop the syndrome.

Challenges of cataract surgery
Dr. Ahmad Khalil explained that first description of exfoliation syndrome in 1927. Then, in 1928 Busacca declared it is not a true exfoliation, but rather, deposits of unknow substance. In 1954 the term pseudo-exfoliation was suggested, which it is still used until nowadays.

He described the exfoliation pupil that is found in the syndrome. He also explained why we also find zonular dehiscence in these patients.

Therefore, in the preoperative evaluation we have to check pupil dilatability, zonular stability (iridodonesis, lens subluxation, zonule dialysis, phacodonesis) and anterior chamber depth. In the intraoperative period we can find further traumatic forces placed on the zonular apparatus, difficulty in extracting nuclear material from the capsular bag, increased risk for anterior capsule tear and increased risk for postoperative capsule phimosis.

Some suggestions may help us during the extrapolatory course: stripping of pupillary synechia ring, single or double hook pupil stretch, mini-sphincterotomies with microscissors, highly cohesive OVD or iris retractors. The devices to address zonular instability are controversial but can helps prevent vitreous prolapse through weakened zonules. During the capsulorhexis, if you performed too small, you may have more chances of complications, however too large may be find difficult in suing capsule rings or retractors and you may find IOL instability. He suggested ideal size of 5 to 5.5 mm. He emphasized that the hydrodissection is really important in these cases.

During the post-operatory period, IOP spikes are more common in exfoliation eyes and more so in eyes with preexisting glaucoma. He also cited other interesting complications that may happen after cataract surgery in exfoliation patients.

Pathophysiology of PXF
Dr. Ursula Schlötzer-Schrehardt explained that the pathophysiology of exfoliation syndrome involves abnormal systemic fibrotic process involving various intra- and extraocular tissues. The body produce excessive production and aggregation of elastic microfibrils into cross-linked fibrillar aggregates.

In terms of genetic different studies identified 7 different genes associated with this syndrome. One of these gene LOXL1 is one of the stronger effects in the disease. She also gave details about the functional significance of LOXL1. This gene is associated with fibrosis of ocular tissues in exfoliation syndrome. It is also associated with elastosis of connective tissues in the syndrome.

She explained that Singapore group re-sequencing the LOXL1 locus and they found that only rs7173049A>G downstream of LOXL1 showed significant and consistent association with exfoliation syndrome.

The Singapore group also found that apart LOXL1 only CYP39P1 gene is associated with the syndrome. CYP39P1 is envolved in the cholesterol metabolism.

In summary, LOXL1 still represents the major genetic effect locus for exfoliation syndrome, and its dysregulated expression causes fibrotic and elastotic tissue alterations, underlying all clinical complications in exfoliation patients. In addition, genetics analyses have identified additional exfoliation genes, disclosing novel metabolic pathways which likely influence disease risk, and which can be potentially targeted to treat fibrotic alterations in exfoliation patients.

Challenges of glaucoma surgery
Dr. Toshihiro Inoue explained some treatment strategies for exfoliation syndrome. He said that we have different options for glaucoma treatment for this type of patient: selective laser trabeculoplasty, trabeculotomy/MIGS, trabeculectomy or Baerveldt glaucoma implant. All of them for open angle cases.

Regarding laser therapy, some previous results showed that SLT may obtain greater IOP reduction and possibly greater success in exfoliation syndrome. However, there also some controversial results. Until nowadays, it remains arguable wheter the surgical results in exfoliation eyes are better than those in primary open angle glaucoma.

For trabeculotomy ab externo for exfoliation glaucoma the success probability is better than in eyes with primary open angle glaucoma. And for cases in which the target IOP level is in the low teens, or for patients who may not tolerate postoperative fluctuations in IOP, we do not recommend trabeculotomy ab externo. He emphasized that this tecnique is faster, easier, and less invasive compared to ab interno.

A prospective study also showed that trabectome surgery presents similar results compared to trabeculotomy ab externo. Trabectome showed to be effective and safe however it is not enough when target IOP level is quite low.

Trabeculectomy presents similar results in comparison with primary open angle glaucoma when lens status are similar.

In conclusion, exfoliation glaucoma takes more aggressive course, set the target IOP lower and needs attention to characteristic complications.

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