Aim: This study investigates whether the post intravitreal injection intraocular pressure (IOP) spike is modifiable with the use of prophylactic apraclonidine and dorzolomide. Methods: The study design was a prospective, randomised controlled trial. 80 eyes undergoing intravitreal injection of anti-VEGF agent were studied. A control group (n = 42) received no IOP lowering drops, and a study group (n = 38) received guttae apraclonidine and dorzolamide 30 to 40 minutes before the intravitreal injection. IOP measurements were taken in both groups using the Perkins tonometer at baseline, immediately before and after the injection, 5 minutes post-injection, and 15 minutes post-injection. Results: Mean IOP immediately post injection in the study group was 26.71 mmHg, and in the control group was 32.73. The main outcome measure was the area under the curve (AUC)—reflecting the trend of IOP post injection. The AUC was lower in the study group compared to the control group (Mann-Whitney U test, p = 0.046). Conclusions: The use of prophylactic apraclonidine and dorzolamide is effective in modifying the post-injection IOP spike. IOP lowering prophylaxis may be considered in patients with a high baseline IOP.