Unraveling the mysteries of macular telangiectasia 2: the intersection of philanthropy, multimodal imaging and molecular genetics. The 2022 founders lecture of the pan American vitreoretinal society.

PURPOSE: Offer a personal perspective on the scientific advances on macular telangiectasia type 2 (MacTel2) since the launch of the MacTel Project in 2005.

DESIGN

Literature review and personal perspective.

METHODS

Critical review of the peer-reviewed literature and personal perspective.

RESULTS

Generous financial support from the Lowy Medical Research Institute laid the foundations of the MacTel Project. MacTel Project investigators used state of the art multimodal retinal imaging and advanced modern biological methods to unravel many of the mysteries surrounding MacTel2. Major accomplishments includes elucidation of the pathogenic role that low serine levels, elevated 1-deoxysphingolipids and other mechanisms induce mitochondrial dysfunction which lead to Müller cell and photoreceptor degeneration; the use of objective measures of retinal structures such as the area of ellipsoid zone disruption as an outcome measure in clinical trials; the demonstration that the ciliary neurotrophic factor slows down retinal degeneration and the development of a new severity scale classification based on multimodal imaging findings.

CONCLUSIONS

MacTel2 is a predominantly metabolic disease characterized by defects in energy metabolism. Despite relatively good visual acuities, MacTel2 patients experience significant visual disability. The Mac Tel Project has been instrumental in advancing MacTel2 knowledge in the past two decades.