Background Hydroxychloroquine (HCQ) is an antimalarial drug, recently used in COVID-19 treatment. Also it is considered over many years the cornerstone in treating systemic lupus erythematosus (SLE) in adults and children. The incidence of retinal affection and retinal toxicity from hydroxychloroquine is rare, but even after the HCQ is stopped, loss of vision may not be reversible and may continue to progress. Fundus autofluorescence (FAF) is one of the screening methods recommended by AAO used for the diagnosis of hydroxychloroquine retinopathy. Our aim is to detect early HCQ-induced retinopathy among SLE patients and the risk factors for its development by using fundus autofluorescence. Results In the present study, 11.3% of the studied patients had significant visual field changes upon testing. Of those, 6.3% had abnormal fundus autofluorescence. We found a significant statistical relation between hydroxychloroquine retinopathy and the duration and cumulative dose of hydroxychloroquine therapy (p value = 0.003) and decreased best-corrected visual acuity of both eyes (p value = 0.000). There was no relationship between HCQ retinopathy detected by fundus autofluorescence and daily dose of HCQ/kg, age, sex, and SLEDAI score. Conclusion Frequency of SLE patients who had confirmed HCQ-induced retinopathy was 6.3%. Hydroxychloroquine could be safely used in all SLE patients regardless of age, sex, and SLE activity. Routine ophthalmological assessment is recommended for SLE patients who received HCQ especially for those who received HCQ longer than 7 years. Fundus autofluorescence is a modern objective tool which is specific for the early detection of HCQ retinopathy.