To the Editor:
We are grateful to Dr Sheth for his interest on this review article and his postulations.
A deeper understanding of how the choroid is involved within the pachychoroid spectrum disorders (PCD) is essential. The choroidal thickening associated with pachydrusen can be diffused or localized under pachydrusen [1]. The retinal pigment epithelium (RPE) is thought to be the primary contributor of the dysfunction of Bruch membrane-RPE-choroid complex and drusen is an early sign of age-related macular degeneration [2]. However, the origin and the initial pathological changes of pachychoroid spectrum disorders is dissimilar. Impairments of choroidal microvasculature and dysregulated choroidal blood flow have been interpreted as the initiator of PCD [3]. The difference of the initiating pathological factor can also explain the difference of the phenotype and genotype of soft drusen and pachydrusen [4]. However, as we indicated in the review, there is comparatively very scanty literature on histopathology of pachydrusen compared to drusen, especially a lack of animal models to systematically investigate the pathological process. More clinical and underlying histopathological evidence are warranted. Moreover, central serous choroidal retinopathy (CSC) or polypoidal choroidal vasculopathy (PCV) do not always co-exist with pachydrusen. The correlation of the distribution of pachydrusen and the leakage on fluorescent angiography of CSC, location of PCV lesions and choroidal neovascularization (CNV) is even weaker. More epigenetics and genetic studies are required to validate the hypothesis that PCV is a gene-mediated disorder, although some genes such as ARMS2 A69S and CFH [4] have been found to be linked to it. Further clinical, molecular and pathological studies are required to understand whether pachydrusen and PCD have a common signalling pathway in the pathological process.
References
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Zhang X, Sivaprasad S. Drusen and pachydrusen: the definition, pathogenesis, and clinical significance. Eye. 2021;35:121–33.
Funding
This work is supported by the National Natural Science Foundation of China [Grant 81570850; Grant 81170859, Grant 82070988] and the Ministry of Science and Technology Foundation of China [Grant 2016YFC1305604].
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XZ—prepared the manuscript. SS—revised the manuscript, approved the final version and agreed to be accountable for all aspects of the work in ensuring that questions relating to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
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Zhang, X., Sivaprasad, S. Response to ‘Comment on ‘Drusen and pachydrusen: the definition, pathogenesis and clinical significance’’. Eye 36, 228 (2022). https://doi.org/10.1038/s41433-021-01577-z
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DOI: https://doi.org/10.1038/s41433-021-01577-z
