The Education Committee carefully selects presentations from the World Glaucoma Congress 2017 in Helsinki for your benefit. This month C. Gustavo De Moraes, MD, MPH introduces the following sessions: Exfoliation syndrome: from the laboratory to the clinic, Finnish glaucoma society 20th anniversary symposium and Glaucoma genomics.
Exfoliation syndrome: from the laboratory to the clinic
This session addressed how basic and clinical sciences have been integrated to translate into enhanced management of exfoliation syndrome (XFS).
First, Mineo Ozaki, MD, PhD, described the history behind the seven main genes reported to be associated with XFS. He started with the first description of the association between LOXL1 common sequence variants and XFS in the Icelandic population. He then mentioned the unexpected results of the study by the Japanese group when trying to replicate the previous one, mainly showing the protective role of certain variants in the Japanese population. He also spoke about risk assessment using a score based upon genetic factors. Based upon the seven loci surpassing GWAS significance for XFS, he presented the results of a risk model the diagnosis of XFS. However, the model had poor utility. He ended by proposing the mechanism of the next generation of genetic associations with XFS: the protesome maturation protein. Downregulation of these genes may be associated with accumulation of XFS material and subclinical forms of the disease.
Terete Borras, PhD, the spoke about possibilities for altering gene expression in XFS. She spoke about the success of gene transferring in animal models for different diseases, including glaucoma. She described the generation of LOXL1 vectors to treat XFS which have shown success in experimental models of the disease.
John Fingert, MD, PhD, spoke about animal models and what they can teach us. He discussed LOLX1 knock-out mice models and how they can be helpful despite its limitations (such as lack of XFS material and no IOP elevation). He described the Lyst mouse and how its phenotype – mainly iris defects – resembles what is seen clinically in XFS. He ended by describing future directions on how to generate better models (e.g.: crosses of known models and environmental exposure, such as UV light) that may help basic scientists better understand the disease and try new therapies.
Robert Fechner, MD, discussed the challenges of cataract surgery in eyes with XFS. Some of the features of XFS that make cataract extraction challenging include small pupils, zonular weakness, difficulty to control IOP, and other post-operative complications (e.g. IOL dislocation). He showed a series of videos illustrating techniques to overcome each of the above challenges. He stressed the importance of going to the operating room aware of the diagnosis of XFS and prepared to deal with its most feared complications.
Richard Lee, MD, PhD spoke about laser and surgical treatment of exfoliation glaucoma. He started by highlighting the high frequency of IOP peaks in this type of glaucoma and how medical treatment may be insufficient to prevent these peaks. He described the success rates of trabeculoplasty (SLT and ALT) in these patients but brought up that many may still need filtering surgery at some points. Both trabeculectomy and tube implants seem to be effective in controlling IOP in XFG, although surgeons should be aware and prepared to treat post-operative complications, particularly excessive inflammation.
Deepak Edward, MD, ended the session talking about the pathology of exfoliation syndrome from a clinician’s perspective. He described the clinical feature of XFS and the importance of looking for them during a complete ophthalmic examination. The focused on the clinical-pathological correlations between slit-lamp findings (including reasons why XFG eyes are more challenging during cataract extraction) and histological characteristics.
Finnish glaucoma society 20th anniversary symposium
The Finnish Glaucoma Society hosted the WGC during its 20th anniversary and presented this symposium with focus on achieving personalized glaucoma care.
Hannu Uusitalo, MD started by describing the history of the Finnish Glaucoma Society, founded in 1997, in addition to its growth and outreach in the past decades. He described the demographic characteristics of the glaucoma population in Finland and how rates of visual impairment have decreased between 1980 and 2000. With increased longevity, the glaucoma population in Finland is expected to grow from 80,000 in 2012 to 120,000 in 20140. He ended his talk by comparing medicine practiced today with what is expected in the near future, that is, a more personalized, patient-driven approach to diagnose and treat diseases, particularly glaucoma.
Ting Aung, FRCS, FRCOphth, PhD, spoke about glaucoma genetics, its recent advances and future directions. He emphasized the important role of GWAS in the understanding of genetic causes of ocular diseases in terms of its presence (yes vs. no) as well as its quantitative traits. He provided an update on GWAS studies in primary open-angle (POAG), angle-closure (ACG), and XF glaucoma. Regarding the latter, he discussed the roles of LOLX1 and CACNA1A. He addressed some limitations of GWAS and concluded his talk by addressing future directions, which included the novel for better technologies, better understanding of pathways, novel targets for therapy, and better phenotyping of glaucoma and its subtypes.
Robert Ritch, MD addressed whether XFS can it be prevented or reversed. He stressed the importance of the Glaucoma Think tank of XFS to recent discoveries in the pathogenesis and potential treatments for XFS/XFG. He called attention to the fact that many cases of XFS are undiagnosed due to inadequate ophthalmic examination and suggested that physician education plays a crucial role in preventing visual impairment from this disease. He concluded that a wide range of treatment options is now becoming available and more is on the way as new developments in the genetics and molecular mechanisms of XFS are unfolded.
This session addressed recent advances in genetic markers for different glaucoma phenotypes.
First, Calvin pang, BSc, DPhil, addressed the implications of genome-wide association studies (GWAS) in glaucoma research. He started by describing the prevalence of glaucoma and the relationship between race and different phenotypes. He described the rapidly evolving field of genetics, which ultimately resulted in GWAS and its application in glaucoma. He reviewed the number of GWAS published studies in primary open-angle glaucoma (POAG), angle-closure glaucoma (ACG), and exfoliation syndrome (XFS). He discussed new discoveries in genetic common variants and their association with intraocular pressure (IOP) and susceptibility for glaucoma. He concluded by discussing the importance of more and larger GWAS and exome/genome sequencing studies to better understand underlying genetic basis for glaucoma phenotypes as well as the need to better characterize these phenotypes for future analyses. These studies may have profound implication on personalized medicine, including new knowledge on the relationship between pharmacologic therapies and response to treatment.
Janey Wiggs, MD, PhD, discussed genotype-phenotype correlations in glaucoma. She emphasized the importance of better understanding such correlations in order to develop clinically-meaningful gene-based diagnostic tests. Of note, there is an important relationship between genetic effect size and frequency of certain glaucoma phenotypes. She described the relationships between different genes associated with glaucoma and the biologic mechanisms underlying these relationships. For instance, some of these mechanisms are related to IOP, cup-to-disc ratio, and normal-tension glaucoma (NTG). She described recent attempts to identify genetic associations in NTG and the chromosomes yet potentially associated with this phenotype. In particular, her recent studies have described specific associations between patterns of visual field defects (e.g.: paracentral scotomas) and common variants. She then discussed that for genetic testing of adult-onset glaucomas, gene-score tests may become a more valuable to approach for risk assessment. She concluded by stressing the importance of deep-phenotyping to enhance the usefulness of genetic data.
Michael Hauser, PhD, addressed the genomics of XFS by first discussing the discovery of LOXL1 as common variant associated with this phenotype. He mentioned the limitation of this association given the influence of race on whether these are protective or risk relationships. He discussed RNA analysis and the recent findings that have helped better understand biologic pathways associated with XFS. He described the worldwide XFS consortium to identify new genetic variants associated with this condition. He then discussed proteasome maturation proteins (POMP) that can be involved in the development of XFS. Of interest, there is an association between POMP and latitude, suggesting significant environmental interactions. He concluded by suggesting potential associations based upon calcium transporters and transmembrane proteins and signaling which warrant further investigation.
Subhabrata Chakrabarti, PhD, concluded the session by discussing genomics of congenital and development glaucoma. He described a set of genes associated with primary congenital glaucoma (PCG) although the majority explains very few cases. In an Indian cohort, he reported that about 60% of cases have unknown mutations. He then described an approach to search for new genes based upon targeted sequencing, exome sequencing, and transcriptome analysis. He described recent findings in animal models that may help explain specific phenotypes of PCGs. He concluded with new insights on the relationship between CYP1B1 and other genes as modifiers under different clinical conditions, as well as cilia-related genes identified through exome sequencing which may help in future understanding of genetic basis of congenital and development glaucomas.