7. Adverse effects.

Study	Follow‐up	Number of people followed up	Adverse effects
Almeida 2008	1 month	74	Quote: "There were 3 dropouts in the treatment group related to ketorolac corneal toxicity, most notably pain attributed to the drops."
Almeida 2012	1 month	162	Quote: “One patient in the ketorolac group was hospitalized with a cardiovascular event and could not complete the follow‐up. Finally, 1 patient on nepafenac had side effects of ocular redness and irritation and could not continue with the study.”
Asano 2008	8 weeks	142	2 "complications" not specified.
Brown 1996	1 month	NR	Adverse effects not reported.
Cervantes‐Coste 2009	6 weeks	60	Quote: "There were no serious treatment‐related adverse events or toxicity related to the use of nepafenac 0.1%."
Chatziralli 2011	6 weeks	138	Quote: "All patients reported pain and ocular discomfort lower than 1/10 on the visual analog scale at all time points."
Donnenfeld 2006	2 weeks	100	Quote: "Use of ketorolac 0.4% for 1 or 3 days provided decreased levels of patient discomfort intraoperatively and postoperatively. Intraoperatively, 3 days of ketorolac 0.4% provided significantly lower discomfort scores than with 1‐hour and placebo dosing (P < 0.001). One day of ketorolac 0.4% also provided significantly reduced intraoperative discomfort scores than with 1‐hour dosing (P = 0.001) and placebo dosing (P < 0.001). Postoperatively, 3 days of ketorolac 0.4% provided significantly lower discomfort scores than 1‐hour dosing or control dosing (P < 0.001) (Figure 5). In addition, patients randomised to 1 or 3 days of ketorolac 0.4% were significantly less likely to require additional intravenous anesthesia (8% in each group) than patients in the control group (40%) (P = 0.008). Twenty percent of patients in the 1‐hour group required additional anesthesia for pain control."
Elsawy 2013	12 weeks	86	Adverse effects not reported.
Endo 2010	6 weeks	62	Quote: "No adverse events were noted in either group."
Italian Diclofenac Study Group 1997	140 days	229	Quote: "No major adverse effects were noted in either group." "Subjective tolerance of the two treatments was good and remained similar throughout the study, although a trend towards increased burning was seen in the diclofenac group."
Jung 2015	1 month	91	Quote: "There were no adverse events except for a mild burning sensation in one patient in the ketorolac group; the symptom was tolerable and did not lead to discontinuation of the medication."
Kraff 1982	between 2.5 and 12 months	492	Quote: "There were no complications that could be ascribed to the use of topical indomethacin other than minor stinging and burning noted by the patients."
Li 2011	1 month	217	Adverse effects not reported.
Mathys 2010	2 months	79	Quote: "There were no adverse events reported by patients using nepafenac."
Miyake 2007	5 weeks	50	Adverse effects not reported.
Miyake 2011	5 weeks	55	NSAIDs: 6 adverse effects: decreased lacrimation, conjunctivitis allergic, abnormal sensation in eye, vomiting (2), constipation. Steroid group: 9 adverse effects: decreased lacrimation, conjunctivitis allergic, retinal haemorrhage, keratoconjunctivitis sicca, chorioretinopathy, influenza, insomnia, diarrhoea, humeral fracture.
Miyanaga 2009	2 months	72	Adverse effects not reported.
Moschos 2012	1 month	79	Adverse effects not reported.
Quentin 1989	180 days	112	Quote: "Diclofenac group: two patients were feeling burning after application of eye drops during the stationary care, for placebo: none. In both groups burning was reported later on in the examinations."
Rossetti 1996	6 months	88	Quote: "Treatment regimens were well tolerated with no evidence of relevant side effects."
Singh 2012	90 days	251	Quote: "No patient deaths were reported during the study. Overall, 13 patients reported other serious adverse events, none of which were related to treatment. Three of the serious adverse events reported in the vehicle group (cardiac failure congestive, coronary artery occlusion, and pancreatitis) led to patient discontinuation; no other serious adverse events led to discontinuation in either treatment group. Separate from the three patients who discontinued due to serious adverse events, four other patients discontinued study participation due to nonserious adverse events. Of these nonserious events, two reported instances of punctate keratitis (one in each treatment group) were assessed as being related to the study drugs. No instances of targeted adverse events (defined as corneal erosions) were reported during the study. Two reports of punctate keratitis and a single report of corneal epithelium defect were assessed as being related to treatment with nepafenac. A single report of punctate keratitis was assessed as being related to treatment with vehicle. No other ocular or nonocular adverse events reported in the study were assessed as being related to the study drugs. In both treatment groups, corneal staining and intraocular pressure were each generally similar at the presurgical baseline and at the day 90 visit (or early exit). Additionally, no safety issues or trends were identified based upon changes from baseline in fundus parameters (retina/macula/choroid and optic nerve) and ocular signs (inflammatory cells, aqueous flare, corneal oedema, and bulbar conjunctival injection). The study results indicate no new clinically relevant risks associated with increasing the dosing of nepafenac from 14 days to 90 days, even in the higher‐risk diabetic patient population."
Solomon 1995	6 months	364	Quote: "During the study, the mean severity of foreign‐body sensation, pain, photophobia, and tearing did not become more than mild (1 +) in any treatment group. This was also true of burning and stinging following treatment instillation (Figure 4). The severity of burning and stinging was significantly greater in the flurbiprofen group on days 4‐20 and 21‐60 and in the indomethacin group on days 1‐3, 4‐20, 21‐60, and 61‐120 than in the vehicle group. At day 1‐3, moderate to severe burning and stinging were reported by 7.0% (16/230) of the patients treated with flurbiprofen, 9.7% (23/237) of the patients treated with indomethacin, and 3.1% (7/224) of the patients treated with vehicle."
Tauber 2006	30 days (3 months mentioned but not reported)	32	Adverse effects not reported.
Ticly 2014	5 weeks	81	One patient withdrew because of burning.
Tunc 1999	2 months	75	Adverse effects not reported.
Tzelikis 2015	1 month	126	Quote: "There were no adverse side effects in either group."
Umer‐Bloch 1983	12 weeks	73	Quote from translation: "40% reported a short burning after using indomethacin eye drops, only rare in patients of the placebo group. One patient had 6 weeks after treatment an allergic blepharitis due to indomethacin. Long‐term: 52 patients were followed for 6 months and 34 patients one year. 4 patients with indomethacin had visual acuity reduction because of a clinically new cystoid edema; 2 of these patients had spontaneous healing after 4‐6 weeks, the other 2 edema cases did not resolve. 2 patients had a new senile macula pathology, and 2 patients had a retinal detachment due to aphakia. Placebo: 2 patients still had an edema after 12 weeks, while one patient developed a new edema later."
Wang 2013	2 months	167	Quote: "No drug‐related adverse events were identified."
Wittpenn 2008	4 weeks	478	Quote: "The most commonly reported adverse events (investigator self‐report) in the ketorolac/steroid group were burning/stinging/tearing (4/268). Transient elevations in intraocular pressure (IOP) were the most commonly reported adverse event in the steroid group (3/278). There were two serious adverse events, both in the steroid group: one patient developed endophthalmitis and one patient died (cause determined to be unrelated to the study medication)."
Yannuzzi 1981	1 year	231	Adverse effects not reported.
Yavas 2007	3 months	179	Adverse effects not reported.
Yung 2007	12 weeks	37	Adverse effects not reported.
Zaczek 2014	6 weeks	152	Quote: "Mild to moderate punctuate epithelial defects of the cornea were found in both groups 3 weeks after treatment.Statistically significantly more patients in the nepafenac group than in the control group had corneal fluorescein staining (20 [26.7%] versus 8 [10.4%]) (PZ.0119). Headache was reported by 3 patients (4.0%) in the nepafenac group and 2 patients (2.6%) in the control group (PZ.9750). No other systemic or local untoward effects were recorded during 3 weeks of treatment in either study group."
Zhang 2008	1 month	220	Adverse effects not reported.