Getting serious with retinopathy: approaching an integrated hypothesis for central serous chorioretinopathy

Development of the prefrontal cortex is believed to play an important role in the maturation of higher cognitive functions such as decision making, cognition and control of part of the neural element of the stress response. The prefrontal cortex undergoes considerable maturation during childhood, including a reduction of synaptic and neural density, a growth of dendrites, and an increase in white matter volume, thereby forming distributed neural networks appropriate for complex cognitive processing, but maturation is not complete until approximately 25 years of age. Serotonin and its receptors (HTRs) play critical roles in brain development and in the regulation of cognition, mood, and anxiety. HTRs are highly expressed in the human prefrontal cortex and exert control over prefrontal excitability. Studies of post-mortem prefrontal brain tissue found distinct developmental patterns of expression of these receptors occurring in early postnatal development and also into adulthood. The general pattern of improved cognitive control and emotion regulation with maturation of the prefrontal cortex, suggests a linear increase in development from childhood to adulthood. Animal studies have shown that dopamine is crucial for communication between the accumbens, amygdala, and prefrontal cortex. Dopamine projections to the prefrontal cortex continue to develop into early adulthood. Central Serous Chorioretinopathy (CSC) is an eye disease affecting people of working age, commonly resulting in repeated unpredictable visually disabling serous retinal detachments and occasionally leading to irreversible reduction in central vision. The disease has been closely linked to the stress response. Despite a concerted effort to understand aetiopathogenesis, disease mechanisms are still largely unclear. This paper, supported by evidence in the literature, proposes a systemic approach to CSC and explains how interactions of the eye with the cerebral cortex could lead to disease. We propose that the lack of development of the neural element of the stress response and in particular the prefrontal cortex is the reason for the absence of CSC in childhood and adolescence. Additionally, we attempt to explain why excess stress hormones do not always result in CSC and why acute attacks occur only once in over half of cases. Finally, we summarise the implications that an integrated systemic hypothesis has for future CSC research and the requirement of a holistic management practice for the identification and treatment of patients with CSC.