The recommendations for the wear and hygiene of ocular prostheses can vary among practitioners, and it is still a controversial theme in the literature. This clinical trial evaluated the microbial load, tissue health of the socket, and the participants’ opinions before and after the use of two hygiene protocols. Thirty ocular prosthesis wearers used either a Daily Protocol (DPt: hygiene once a day) or Weekly Protocol (WPt: hygiene once a week) for 5 weeks with a washout of 7 days. The microbial load was quantified by the colony-forming unit count of the aerobic bacteria,
Candida spp.,
Staphylococcus spp., and Gram-negative bacteria. The tissue health of the socket was evaluated by scores, and patients’ opinion of the protocols was evaluated using the analogic visual scale (VAS). Data were analyzed by ANOVA Repeated Measures, Friedman, Cochran’s Q Test, Wilcoxon, Fisher, and Pearson’s chi-square tests considering
p < 0.05. There was no difference in the microbial load of the microorganisms (
p > 0.05). Both protocols improved socket inflammation (
p = 0.005) and discharge (
p < 0.001); DPt improved edema (
p = 0.021) and crusting (
p = 0.020). There was no difference in patients’ rating responses (VAS) for all the questions of patients’ opinion (Q1:
p = 1.0; Q2:
p = 1.0; Q3:
p = 1.0; Q4:
p = 1.0; Q5:
p = 1.0; Q6:
p = 0.317; Q7:
p = 1.0; Q8:
p = 0.159). There was a correlation between eye drops/edema (
p = 0.030), eye drops/pain (
p = 0.016), microbial load with discharge, inflammation, eyelid edema, and pain. Inflammation was correlated with edema at baseline (
p < 0.001) and after DPt (
p = 0.018), and with crusting at baseline (
p = 0.003); edema was correlated with crusting at baseline (
p < 0.001); crusting was correlated with discharge after WPt (
p < 0.001). The protocols showed no effects on the microbial load of the anophthalmic socket and ocular prosthesis. However, better tissue health and patient acceptance were observed after both regimens.
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