The accuracy and the overall performances of ophthalmic instrumentation, where specific analysis of eye images is involved, can be negatively influenced by invalid or incorrect frames acquired during everyday measurements of unaware or non-collaborative human patients and non-technical operators. Therefore, in this paper, we investigate and compare the adoption of several vision-based classification algorithms belonging to different fields, i.e., Machine Learning, Deep Learning, and Expert Systems, in order to improve the performance of an ophthalmic instrument designed for the Pupillary Light Reflex measurement. To test the implemented solutions, we collected and publicly released PopEYE as one of the first datasets consisting of 15 k eye images belonging to 22 different subjects acquired through the aforementioned specialized ophthalmic device. Finally, we discuss the experimental results in terms of classification accuracy of the eye status, as well as computational load analysis, since the proposed solution is designed to be implemented in embedded boards, which have limited hardware resources in computational power and memory size.