To explore the impact of different image registration algorithms on the diagnosis of visual path damage in patients with primary open angle glaucoma (POAG), 60 cases of suspected POAG patients were selected as the research objects. Shape-preserving scale invariant feature transform (SP-SIFT) algorithm, scale invariant feature transform (SIFT) algorithm, and Kanade-Lucas-Tomasi (KLT) algorithm were compared and applied to MRI images of 60 POAG patients. It was found that the SP-SIFT algorithm converged after 33 iterations, which had a higher registration speed than the SIFT algorithm and the KLT algorithm. The mean errors of the SP-SIFT algorithm in the rotation angle, X-direction translation, and Y-direction translation were 2.11%, 4.56%, and 4.31%, respectively. Those of the SIFT algorithm were 5.55%, 9.98%, and 7.01%, respectively. Those of the KLT algorithm were 7.45%, 11.31%, and 8.56%, respectively, and the difference among algorithms was significant ( P < 0.05 ). The diagnostic sensitivity and accuracy of the SP-SIFT algorithm for POAG were 96.15% and 94.34%, respectively. Those of the SIFT algorithm were 94.68% and 90.74%, respectively. Those of the KLT algorithm were 94.21% and 90.57%, respectively, and the three algorithms had significant differences ( P < 0.05 ). The results of MRI images based on the SP-SIFT algorithm showed that the average thickness of the cortex of the patient’s left talar sulcus, right talar sulcus, left middle temporal gyrus, and left fusiform gyrus were 2.49 ± 0.15 mm, 2.62 ± 0.13 mm, 3.00 ± 0.10 mm, and 2.99 ± 0.17 mm, respectively. Those of the SIFT algorithm were 2.51 ± 0.17 mm, 2.69 ± 0.12 mm, 3.11 ± 0.13 mm, and 3.09 ± 0.14 mm, respectively. Those of the KLT algorithm were 2.35 ± 0.12 mm, 2.52 ± 0.16 mm, 2.77 ± 0.11 mm, and 2.87 ± 0.17 mm, respectively, and the three algorithms had significant differences ( P < 0.05 ). In summary, the SP-SIFT algorithm was ideal for POAG visual pathway diagnosis and was of great adoption potential in clinical diagnosis.