Age-related macular degeneration is a common disorder resulting in loss of vision. At one time, the neovascular manifestations were the most feared, but with availability of treatments for neovascularization, and with the increasing lifespan of people in developed countries, geographic atrophy is becoming a larger problem. Indeed, atrophy is a common outcome for patients treated for neovascular disease. In atrophy, there is loss of the retinal pigment epithelium (RPE), and in histologic specimens, there is loss of the underlying choriocapillaris.1,2
The relationship between the choriocapillaris and the RPE seems to be complex. The RPE secretes trophic factors such as vascular endothelial growth factor to maintain the choriocapillaris. However, loss of the choriocapillaris potentially could adversely affect the health of the overlying RPE and thus affect secretion of trophic factors. We and others have documented loss of choriocapillary segments in older patients, particularly with basal linear deposits and subretinal drusenoid deposits.3,4 This same class of patients has demonstrable defects in optical coherence tomography angiography imaging of choriocapillaris flow.5 However, these patients also have drusen, subretinal drusenoid deposits, and pigmentary changes, which may variably affect the imaging of the choriocapillaris. It is possible that in geographic atrophy in age-related macular degeneration, there can be artifacts that compromise imaging of the choriocapillaris caused by structures such as drusen.6 In addition, older patients often have media opacities, such as cataracts, that can affect imaging.
To help understand if flow abnormalities in the choriocapillaris can occur without the confounding effects of media opacity, RPE pigmentary abnormalities, or thick accumulations of extracellular deposit, we could look at conditions that are associated with RPE atrophy before atrophy actually being present.7 Flow abnormalities in these eyes may offer clues the relationship between the choriocapillaris and the RPE. Two such diseases are maternally inherited diabetes and deafness (MIDD) and pseudoxanthoma elasticum. In a small study examining these conditions, widespread abnormalities in choriocapillaris flow were detected while similar changes were not seen in 55 control normal eyes.7 This is an interesting finding. Both maternally inherited diabetes and deafness and pseudoxanthoma elasticum are believed to develop a “pattern dystrophy.” However, it is possible that the pattern dystrophy appearance may be the result of poor choriocapillaris flow. In addition, a mechanism of disease was outlined in which abnormalities of the RPE leading to less secretion of trophic factors could be linked to choriocapillaris flow, which in turn could damage the overlying RPE cells. It is easy to propose that a self-reinforcing cycle could be set up, ultimately resulting in atrophy and tissue loss. Thus, there are many interesting lines of research that could be undertaken as a consequence of the new findings in this study.
Drs. Finsterer and Zarrouk-Mahjoub wrote a letter that is difficult to parse through. They seem to miss the much of the intent of my article. Instead they want to state that MIDD is not only due to m.3243A > G mutation but to other mutations, which while interesting has no relevance to the focus of the article. A second point they want to establish is that MIDD can affect organs other than the eyes, which is widely known and already is mentioned in my article. They stated that choriocapillary perfusion defects could be due to a primary metabolic vasculopathy, which certainly is a possibility and is inherent in the discussion of choriocapillaris-RPE interactions as mentioned above. Finally, they stated in their summary that heteroplasmy rates and severity of phenotype are usually poor. It is not evident how this statement is germane to the focus of my article.
Fleshing out the letter by Drs.