Postmarketing safety surveillance of dexamethasone intravitreal implant in the treatment of visual impairment due to diabetic macular edema in India
Authors: Nair Unnikrishnan , Gupta Vishali , Sharma Mohita , Joshi Shrinivas , Sudhalkar Aditya , Altangerel Undraa , Bai Yan ,   for the India Ozurdex Postmarketing Surveillance Study Group, Agarwal Manisha , Balakrishnan Divya , Banker Alay , Borse Nishikant , Gupta Vishali , Joshi Shrinivas , Khatri Manoj , Myneni Jyotsna , Nagpal Manish , Nair Unnikrishnan , Rajesh R. , Raval Vishal R. , Reddy Rajarami , Salhotra Sudhir , Saswade Manoj , Sharma Mohita , Singh Indu , Sinha Anshuman , Sudhalkar Aditya 
Published: October 2020

Abstract
Background
Diabetic macular edema (DME) is the most common cause of vision loss in diabetic patients. As India has the second largest population of diabetic patients worldwide, availability of various treatment options for DME is essential. This postmarketing surveillance study was conducted to fulfill a commitment to the Regulatory Authority of India to examine the safety of dexamethasone intravitreal (DEX) implant over 1 year in Indian patients with DME receiving ≥1 DEX implant for DME-related visual impairment in clinical practice.

Methods
This observational, prospective, non-interventional study enrolled patients aged ≥18 years scheduled to receive DEX implant for DME-related visual impairment. Baseline demographics, medical history, date of last DEX implant injection, detailed information about adverse events (AEs), AEs of special interest (AESIs), serious AEs (SAEs), and adverse drug reactions (ADRs) reported during postinjection visits and investigator telephone calls were collected. Primary outcome measures were treatment-emergent AE (TEAE), AESI, SAE, and ADR occurrences.

Results
Of the enrolled patients (19 sites throughout India; n = 250), 84 had received DEX implant previously; mean (standard deviation; SD) duration between prior and study entry dose was 199.4 (156.0) days, and 91 (36.4%) had ≥1 prior ophthalmic condition. Over a mean of 182.6 (88.6) follow-up days (min–max: 0–364 days), 22 TEAEs were reported by 7 (2.8%) patients, 6 of whom had previously received DEX. AESIs of increased IOP (n = 3, 6 events) and glaucoma (n = 1, 1 event) were considered non-serious, of mild/moderate severity, and related to DEX treatment. Eyelid ptosis was reported in 1 patient (1 event). Nonocular AEs included cardiac AEs (n = 3, 4 events), pyrexia (n = 1, 2 events), and dyspnea (n = 1, 2 events). Three (1.2%) patients had 12 serious AEs; most were cardiac disorders; all were unrelated to DEX treatment. Two (0.8%) deaths were considered unrelated to treatment.

Conclusions
Based on voluntary reporting of adverse events in this surveillance study, DEX implant for treatment of DME-related visual impairment in the Indian population demonstrated a favorable safety profile with few treatment-related TEAEs (none were considered serious) during the 1-year follow-up. These data supplement previous findings and confirm the safety of DEX implant in this population during usual clinical practice.

Trial registration
World Health Organization Clinical Trials Registry: CTRI/2017/04/008396. Registered 24 April 2017.