The analgestic efffect of Diclofenac Sodium 0.1% Eye Drops and a combination of Diclofenac Sodium 0.1% Eye Drops and oral Diclofenac Sodium sustained-release 75mg tablets on pain related to intravitreal injections will be evalutated.

Pain perception will be assessed by the Short Form of the McGill Pain Questionnaire.

Intravitreal injection (IVI) is a preferred route of administration of drugs in the posterior segment of the eye. Intravitreal injection of anti-VEGFs constitutes the mainstay for the treatment of various retinal diseases such as AMD, RVO, DME etc.

The procedure of the IVI is, however, associated with a level of discomfort for the patient.

Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit the activity of cyclooxygenase-1 and cyclooxygenase-2, and thereby, the synthesis of prostaglandins and thromboxanes. Cyclooxygenase-2 inhibition leads to the anti-inflammatory, analgesic and antipyretic effects of NSAIDs.

Ophthalmic NSAIDs constitute an established and effective treatment option for the management of inflammation and pain associated with cataract surgery and of pain associated with corneal refractive surgery, for inhibition of intraoperative miosis and for the treatment of seasonal allergic conjunctivitis.

The primary goal of this study is to assess the analgesic effect of DIclofenac 0.1% Eye Drops a topical NSAID, as well as a combination of Diclofenac 0.1% Eye Drops and oral Diclofenac Sodium sustained-release (SR) 75mg tablets on pain related to intravitreal injections immediately after and up to six hours post-IVI.

A number of patients scheduled to undergo IVIs of anti-VEGFs will be randomized and divided in three groups. All patients must have already undergone at least one IVI. In patients receiving IVIs in both eyes only one eye will be included in the study.

The patients of the first group will receive placebo pill 4 hours before the IVI and Diclofenac 0.1 % Eye Drops 45 minutes prior to the injection.

The patients of the second group will recieve oral Diclofenac Sodium SR 75mg/tb 4 hours prior to the injection and Diclofenac 0.1% Eye Drops 45 minutes prior to the injection.

The patients of the third group will receive placebo pill 4 hours and Artificial Tears 45 minutes prior to the injection.

Patients will be required to complete the greek version of the short form McGill Pain Questionnaire (SF-MPQ) comprising of the Visual Analogue Scale, the main component of the SF-MPQ and the Present Pain Intensity Scale immediately after the injection and 6 hours post-IVI.

Inclusion Criteria:

• All participants will be patients of the Medical Retina Department of our Clinic, who are scheduled to receive IVIs of ranibizumab (Lucentis; Novartis Pharma S.A.S., Huningue, France) or aflibercept (Eylea; Bayer Healthcare Pharmaceuticals, Berlin, Germany) in one eye and had already undergone at least one IVI of an anti-VEGF agent.

Exclusion Criteria:

• History of previous eye surgery other than cataract extraction surgery, herpetic eye disease, uncontrolled glaucoma, uveitis, active conjunctivitis, keratitis and bullous keratopathy, a previously known allergic response to diclofenac or other NSAIDs and salicylates, any contraindication to NSAIDs administration such as cardiovascular disease, gastrointenstinal disease with risk of GI ulceration,bleeding and perforation, renal and hepatic disease and any systemic or topical use of NSAIDs or any use of sedative medications within 7 days from the visit and during the day of IVI.
• Patients with poor cooperation in understanding and answering the questions of the SF-MPQ, including the visual analogue scale (VAS).
• Unsuccessful blinding