Review Article Conjunctivitis: A Systematic Review Amir A. Azari, MD1,2, Amir Arabi, MD, MPH1,2 1Ophthalmic Research Center, Research Institute for Ophthalmology and Vision Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran 2Department of Ophthalmology, Torfeh Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran ORCID: Amir A. Azari: https://orcid.org/0000-0003-2013-3284 Abstract Conjunctivitis is a commonly encountered condition in ophthalmology clinics throughout the world. In the management of suspected cases of conjunctivitis, alarming signs for more serious intraocular conditions, such as severe pain, decreased vision, and painful pupillary reaction, must be considered. Additionally, a thorough medical and ophthalmic history should be obtained and a thorough physical examination should be done in patients with atypical findings and chronic course. Concurrent physical exam findings with relevant history may reveal the presence of a systemic condition with involvement of the conjunctiva. Viral conjunctivitis remains to be the most common overall cause of conjunctivitis. Bacterial conjunctivitis is encountered less frequently and it is the second most common cause of infectious conjunctivitis. Allergic conjunctivitis is encountered in nearly half of the population and the findings include itching, mucoid discharge, chemosis, and eyelid edema. Long-term usage of eye drops with preservatives in a patient with conjunctival irritation and discharge points to the toxic conjunctivitis as the underlying etiology. Effective management of conjunctivitis includes timely diagnosis, appropriate differentiation of the various etiologies, and appropriate treatment. Keywords: Allergic; Bacterial; Conjunctivitis; COVID-19; Coronavirus; Viral; Toxic J Ophthalmic Vis Res 2020; 15 (3): 372–395 INTRODUCTION by engorgement of the blood vessels, ocular discharge, and pain. Many subjects are affected Conjunctivitis is characterized by inflammation and with conjunctivitis worldwide, and it is one of swelling of the conjunctival tissue, accompanied the most frequent reasons for office visits to general medical and ophthalmology clinics. More Correspondence to: than 80% of all acute cases of conjunctivitis are Amir A. Azari, MD. Ophthalmic Research Center, reported to be diagnosed by non-ophthalmologists Research Institute for Ophthalmology and Vision Science, Shahid Beheshti University of Medical including internists, family medicine physicians, Sciences, No. 23, Paidarfdard St., Boostan 9 St., Pasadaran Ave., Tehran 16666, Iran. Email: [email protected] This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which Received: 18-02-2020 Accepted: 25-04-2020 allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms. Access this article online Website: https://knepublishing.com/index.php/JOVR How to cite this article: Azari AA, Arabi A. Conjunctivitis: A Systematic DOI: 10.18502/jovr.v15i3.7456 Review. J Ophthalmic Vis Res 2020;15:372–395. 372 © 2020 JOURNAL OF OPHTHALMIC AND VISION RESEARCH | PUBLISHED BY PUBLISHED BY KNOWLEDGE E Conjunctivitis; Azari and Arabi pediatricians, and nurse practitioners.[1] It is extremely important to differentiate This imposes a great economic burden conjunctivitis from other causes of “red eye” to the healthcare system and occupies a associated with severe sight- or life-threatening great proportion of the office visits in many consequences such as acute angle closure medical specialties. It is estimated that the glaucoma, uveitis, endophthalmitis, carotid- cost of treating bacterial conjunctivitis is cavernous fistula, cellulitis, and anterior segment $857 million annually in the United States tumors. alone.[2] It has been reported that nearly 60% of METHODS all patients with acute conjunctivitis receive antibiotic eye drops; and the vast majority receive The scientific literature published as of their prescription from a non-ophthalmologist February 2020 was thoroughly reviewed by physician. For example, 68% of patients searching PubMed, the ISI web of knowledge who visited a physician at an emergency database, and the Cochrane library using room received antibiotic eye drops while this relevant keywords. The following keywords figure dropped to 36% for those who saw an were used: ”bacterial conjunctivitis”, ”viral ophthalmologist.[1] Interestingly, patients from conjunctivitis,” ”allergic conjunctivitis”, ”treatment a higher socioeconomic status were more of bacterial conjunctivitis”, and ”treatment of likely to receive and fill a prescription for their viral conjunctivitis”. No language restriction was conjunctivitis.[1] applied. There are several ways to categorize Articles published between March 2013 and conjunctivitis; it may be classified based on February 2020 were screened and those that etiology, chronicity, severity, and extend of provided the best evidence-based information involvement of the surrounding tissue. The were included in this review. A total of 167 articles etiology of conjunctivitis may be infectious or were finally included. The first study was published non-infectious. Viral conjunctivitis followed by in 1964 and the last study was published in 2020. bacterial conjunctivitis is the most common cause of infectious conjunctivitis, while allergic History and clinical examination and toxin-induced conjunctivitis are among the most common non-infectious etiologies. How to diagnose conjunctivitis In terms of chronicity, conjunctivitis may be divided into acute with rapid onset and Conjunctival injection or “red eye” is a shared duration of four weeks or less, subacute, and presentation for many ophthalmic diseases, [3] chronic with duration longer than four weeks. and it accounts for up to 1% of all primary Furthermore, conjunctivitis may be labeled care office visits.[6] The clinicians, whether as severe when the affected individuals are ophthalmologist or not, must be aware that “red extremely symptomatic and there is an abundance eye” may be the presenting sign for serious of mucopurulent discharge. Conjunctivitis may eye conditions such as uveitis, keratitis, or be associated with the involvement of the scleritis, or it may be secondary to more benign surrounding tissue such as the eyelid margins conditions that are limited just to the conjunctival and cornea in blepharoconjunctivitis and viral tissue (e.g., conjunctivitis or subconjunctival keratoconjunctivitis, respectively. hemorrhage). Traditionally, it was believed that Additionally, conjunctivitis may be associated more harmful ophthalmic disorders are associated with systemic conditions, including immune- with disturbances in vision, disabling pain, and related diseases [e.g., Reiter’s, Stevens-Johnson photophobia.[6] However, in a recent large meta- syndrome (SJS), and keratoconjunctivitis analysis,[6] anisocoria and mild photophobia sicca in rheumatoid arthritis], nutritional were significantly associated with “serious deprivation (vitamin A deficiency), and eye conditions”; the presence of these two congenital metabolic syndromes (Richner- signs could discover 59% of cases of “serious Hanhart syndrome and porphyria)[4, 5] (Table eye conditions”, including anterior uveitis and 1). keratitis. Table 2 provides a summary of the JOURNAL OF OPHTHALMIC AND VISION RESEARCH VOLUME 15, ISSUE 3, JULY-SEPTEMBER 2020 373 Conjunctivitis; Azari and Arabi Table 1. Guideline to help differentiate the major etiologies in conjunctivitis Clinical history and exam findings Most probable etiologies Alarming signs and symptoms Decreased vision, severe pain, painful pupillary reaction, Uveitis, scleritis, keratitis, glaucoma, orbital, or parasellar anisocoria, orbital signs pathology Chronicity Sudden onset, lasting less than four weeks Infectious conjunctivitis, allergic conjunctivitis, acute systemic reactions (SJS/TEN) Insidious onset, chronic course Conjunctivitis associated with systemic diseases, toxic conjunctivitis, allergic conjunctivitis Recurrent course Allergic conjunctivitis, conjunctivitis associated with systemic diseases Associated symptoms Skin lesions, arthropathy, genito-perineal involvement, Conjunctivitis associated with systemic diseases, infectious oropharyngeal lesions diseases Drug history Long-term eye drop usage Toxic conjunctivitis, allergic conjunctivitis Recent initiation of a systemic medication Acute systemic reactions (SJS/TEN) SJS, Stevens-Johnson syndrome; TEN, toxic epidermal necrolysis main etiologies of “red eye” and their clinical the palpebral conjunctiva for the presence of characteristics. pseudomembranes, symblepharon, papilla or follicles, and the corneal tissue for the presence of How to distinguish infectious conjunctivitis opacities and infiltrates is absolutely essential. from non-infectious conjunctivitis Some of the clinical signs and symptoms that are used to help diagnose infectious conjunctivitis Obtaining history from patients who present include the following: eye discharge, conjunctival with conjunctivitis is crucial in order to arrive injection, presence of red eye(s), eyelashes being at the correct diagnosis. A focused ocular stuck together in the morning, grittiness of the history should include the following: onset and eye(s), eyelid or conjunctival edema, and history of [7] duration of symptoms; laterality; impairment of contact with