Background Screening of early hydroxychloroquine (HCQ) maculopathy is important to prevent permanent structural and functional retinal damage. Spectral domain optical coherence tomography (SD-OCT) ultra-high-resolution imaging and speed allows better visualization of retinal architecture and measurement of the thickness of the retinal layers.Objective The aim of this study was to evaluate the macular ganglion cell complex (GCC) thickness by using SD-OCT for screening of early HCQ maculopathy.Patients and methods A total of 128 patients were included in the present study. They were divided into two groups: HCQ group, comprising 128 eyes of 64 patients treated with HCQ, and a control group, comprising 128 eyes of 64 healthy individuals. Average, minimum, and sectorial macular GCC thickness and photoreceptor layer (PL) integrity were compared between the two study groups. Correlations between GCC thickness and duration of HCQ use, PL integrity, uncorrected visual acuity, and best-corrected visual acuity in the HCQ group were analyzed.Results There were no statistically significant differences between the two groups regarding the average, minimum, and sectorial macular GCC thickness. However, a statistically significant difference between the two groups was found regarding the PL integrity. In addition, the PL integrity was found to have the highest independent correlation with the average macular GCC thickness, followed by the duration of treatment with HCQ, and lastly, the uncorrected visual acuity.Conclusion Unique SD-OCT findings in the retina can identify early HCQ retinopathy and may play a role as a complementary objective tool in HCQ maculopathy screening.