The pathophysiology of age-related macular degeneration (AMD) is complex, and the underlying mechanisms are not yet fully understood. In recent years, an infectious hypothesis in the pathogenesis of AMD has emerged, suggesting a link between various infectious agents and AMD. Findings from a group of French researchers, which were published in Ophthalmology Science, determined that the currently available data do not clearly speak in favor of or against the implication of infectious agents in AMD.

This study suggests avenues of research to enrich the data currently available, which still does not provide an insufficient level of evidence to conclude whether or not infectious agents are involved in AMD. Photo: Larsen PP, et al. Ophthalmol Sci. November 30, 2024. Click image to enlarge.

All types of study design, infectious agents, AMD diagnostic methods and AMD stages were considered. Articles dealing with the oral and gut microbiota were not included. Two investigators independently screened the 868 articles obtained by the researchers’ algorithm and the reference lists of selected studies. In total, 40 articles were included, among which 30 were on human data, nine were animal studies, six were in vitro experiments and one was a hypothesis paper (sometimes with several data types in the same article). Of these, 27 studies were published after 2010, which highlighted a growing interest in recent years.

A wide range of infectious agents has been investigated, including various microbiota (nasal, pharyngeal), eight bacteria, six viral species and one yeast. Among them, most have been investigated anecdotally.

The researchers found that only Chlamydia pneumoniae, cytomegalovirus and hepatitis B virus received more attention, with 17, six and four studies, respectively. Numerous potential pathophysiological mechanisms have been discussed, including 1) an indirect role of infectious agents (i.e., a role of infections located distant from the eye, mainly through their interactions with the immune system) and 2) a direct role of some infectious agents implying potential infection of various cell types within AMD-related tissues.

“Despite these numerous hypotheses, the level of evidence remains low even for the three most studied pathogens,” the study authors wrote in their paper.

The team suggested that future studies combining human, animal and in vitro experiments for the same pathogen are needed to improve our understanding. “Experimental studies will be decisive to decipher potential underlying mechanisms and could help to guide the choice of AMD stage to investigate for each suspected pathogen,” they noted. “Overall, an intensification of research efforts on the infectious hypothesis and AMD seems essential given the potential repercussions in terms of diagnosis, prevention and treatment.”