AL and age were well-established factors that can lead to visible changes in the fundus. Regarding the AL, elongated eyeballs could cause a decrease in microvasculature density in the macula,
20 visible fundus tessellations,
21 and deep learning detectable changes in choroidal thickness.
22 In addition, various structural abnormalities involving the optic disc were found associated with elongated AL, including PPA,
23 tilted disc, and enlarged optic disc crescent.
24,25 On the other hand, aging could affect the appearance of the fundus captured by CFP with multiple means, which include influencing the color presented in the photos, altering the retinal microvasculature, increasing the visibility of large choroidal vessels due to tessellation,
11,26 and even causing age-related macular degeneration.
27 In addition to AL and age, Korot et al.
8 demonstrated that CFP could be used to predict sex via deep learning models, suggesting the presence of sex-related differences in the appearance of the fundus. Ilanchezian et al.
28 found that the optic disc and the macula were most relevant in fundus-based prediction of sex, with the former providing information on predicting the male sex and the latter on predicting the female sex. Therefore, to more accurately predict AL using CFP, we investigated the effects of adding age and sex as input parameters to the deep learning models and found an improved accuracy mainly attributed to the addition of age as the predictor. This finding suggests that AL and age may share some common characteristics regarding the fundus appearance. Analytical capabilities of CNNs have been proven to extend beyond current human capability, and these CNN models could pick up on both nonhuman-interpretable features and are indicative of meaningful medical information contained in CFP.
29 The incorporation of age as an additional predictor, while being proved to be advantageous, pointed to the inherent challenge of distinguishing certain specific features solely from the available data, hinting at the potential necessity for supplemental external information. It is crucial to emphasize that the finding needs further substantiation through additional pathologic evidence; nevertheless, it uncovered a noteworthy morphologic observation and provided a clear trajectory for prospective research endeavors.