Background: Dry eye disease [DED] results in symptoms of discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface. Biological tear substitutes, a blood derivative, demonstrated good efficacy in improvement of symptoms and ocular surface staining reduction in patients with moderate-to-severe dry eye disease.  
Aim of the work: To evaluate the efficacy of autologous serum [AS] eye drops [20%], platelet rich plasma [PRP] eye drops [20%], for treatment of severe DED and comparing their results with each other.
Patients and methods: A prospective comparative study included 120 eyes of 60 patients with severe DED aged 18 - 67 years. Patients divided into 2 groups according to treatment protocol: Group I:  60 eyes of 30 patients treated with autologous serum eye drops, Group II: 60 eyes of 30 patients treated with autologous platelet rich plasma eye drops. They underwent a comprehensive ophthalmic examination, evaluation of best corrected visual acuity [BCVA], tear break-up time [TBUT], Schirmer's test, corneal fluorescein staining [CFS; oxford grading scale], and level of Conjunctival hyperaemia [Efron grading scale] during 6 weeks of treatment. Conjunctival impression cytology [CIC] studied before and after treatment.
Results: Statistically significant larger improvement in BUT [p=0.001], Schirmer's test [p < 0.001] and significantly larger reduction of CFS [p < 0.001] in Group II compared to Group I at six weeks after treatment. Likewise, a significant improvement of Nelson grading of CIC [p =0.04] was found in Group II. Greater reduction of conjunctival hyperaemia but not statistically significant [p = 0.275], also the improvement in BCVA [log MAR], [p=0.242], in Group II compared to Group I at six weeks after treatment.
Conclusion: PRP eye drops induces a more significant improvement in different DED signs than AS in treatment of severe dry eye disease.