What to Do When That Red Eye Will Not Go Away

How to properly identify the many faces of chronic conjunctivitis.

By Nicholas Colatrella, OD, and Jeffrey Varanelli, OD

Chronic conjunctivitis can be one of the most frustrating reasons patients present to our offices. The chronic nature of symptoms can be irritating to patients, and relief is typically not seen with over-the-counter treatment options. Unsuccessful therapeutic remedies may further cloud the clinical picture, and patients can become despondent due to the lack of resolution of symptoms.

We use a definitive algorithm that can help the practitioner accurately diagnose all forms of chronic conjunctivitis, greatly increasing the chance of a successful therapeutic outcome (see Chronic Conjunctivitis Diagnosis Algorithm bellow). It works by classifying conjunctivitis in four distinct categories:

• Time course
• Morphology
• Anatomic localization
• Type of discharge

Proper use of this algorithm has been shown to lead to an accurate diagnosis in 95% of cases.1 After the correct diagnosis is established, treatment is typically straightforward and successful.


Three weeks is the approximate upper limit in which most cases of viral or bacterial conjunctivitis resolve without treatment. Any case of conjunctivitis that has been present for longer than 3 weeks should be considered chronic. Acute conjunctivitis typically resolves, with or without treatment, within 3 weeks. Causative organisms typically include herpes simplex virus, enteroviruses, and adenoviruses. Other causes can include chlamydial infections, ocular surface disease, and all forms of giant papillary conjunctivitis.1-3


Determining the morphologic characteristics correctly is probably the single most important part of the diagnostic process, as it truly helps to identify clinical findings. Morphology can be differentiated into five categories: papillary, giant papillary, follicular, membranous, and cicatrizing.1-3

Papillary (Figure 1)

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Figure 1. Papillary reaction.

Every type of conjunctivitis will have some form of papillary hypertrophy. Papillae can be described as elevations of the conjunctiva with a central core blood vessel. As the infiltration of inflammatory cells thickens the conjunctiva, individual papillae are created by septae. These septae are the fibrous connections between the conjunctival epithelium and the underlying substantia propria. Each papilla is then seen as a red dot, which represents the core blood vessel viewed on end.1,3 Clinical presentations that fall under this category include occult foreign body and floppy eyelid syndrome, mostly affecting the upper tarsal conjunctiva.

Giant Papillary (Figure 2)

© 2017 American Academy of Ophthalmology

Figure 2. Giant papillary reaction.

Giant papillary changes occur as a result of a breakdown of the individual septae that divide the papillae. These multiple individual papillae then merge to form a giant papilla, which is generally greater than 1 mm in size. Giant papillae most commonly occur on the upper tarsal conjunctiva, and they have flat tops that fit together, creating the characteristic “cobblestone” appearance.1,3 Giant papillary conjunctivitis (GPC) presents in two distinct forms: primary and secondary. Primary GPC includes vernal keratoconjunctivitis and atopic keratoconjunctivitis. Secondary GPC is most often mechanical in nature, occurring typically as a result of contact lens wear, ocular prostheses, or exposed sutures.1,3

Follicular (Figure 3)

© 2017 American Academy of Ophthalmology

Figure 3. Follicular reaction.

In contrast to papillae, follicles have a circumferential blood vessel and a clear center. These dome-shaped conjunctival elevations are collections of mononuclear inflammatory cells that are organized in a fashion similar to follicles within lymph nodes. Chronic follicular conjunctivitis can be due to molluscum contagiosum virus or Chlamydia trachomatis infection or as a result of prolonged use of topical medications, creating a toxic reaction.1,3,4

Membranous or Pseudomembranous (Figure 4)

© 2017 American Academy of Ophthalmology

Figure 4. Pseudomembranous reaction.

Membranes and pseudomembranes are sheets composed of networks of fibrin and inflammatory cells that form a layer over the surface of the conjunctiva. True membranes include the growth of capillaries from the conjunctiva into the membrane, but pseudomembranes are avascular. Ligneous conjunctivitis, which most commonly affects the palpebral conjunctiva, is noted for its thick, ligneous lesions. This is the only chronic membranous form of conjunctivitis.1,3,5

Cicatrizing (Figure 5)

© 2017 American Academy of Ophthalmology

Figure 5. Cicatrization.

Cicatrization, or progressive conjunctival scarring, can be seen in some instances of chronic conjunctivitis. Clinical signs typically include subconjunctival scars in a stellate or linear pattern, shortening of the fornices, and formation of symblepharon and eventually ankyloblepharon. If the scarring progresses, cicatricial entropion can occur. In severe cases, this can lead to a loss of conjunctival goblet cells, which in turn causes conjunctival and corneal keratinization. Although rare, cicatrization can result from Stevens-Johnson syndrome, ocular pemphigoid, chemical (alkali) burn, or trachoma.1,6,7


Different forms of conjunctivitis tend to affect different external areas of the eye. Determining the area that is predominantly affected can contribute to an accurate diagnosis. Although in most cases chronic conjunctivitis is bilateral, it is often asymmetric. Causes of unilateral chronic conjunctivitis include lacrimal drainage infections (such as chronic dacryocystitis and canaliculitis), masquerade syndromes, and even factitious conjunctivitis (eg, mucus fishing syndrome).2,3


Chronic conjunctivitis may manifest with a number of morphologies. Relying on a limited differential diagnosis can help eye care providers accurately and efficiently diagnose and initiate treatment for this disease.

In some cases, such as in chronic blepharitis and atopic keratoconjunctivitis, the conjunctivitis involves the eyelids as well as the conjunctiva. Other forms, such as vernal keratoconjunctivitis, trachoma, and superior limbic keratoconjunctivitis, primarily affect the upper palpebral conjunctiva.1,2 Cases that predominantly affect the lower palpebral conjunctiva include inclusion conjunctivitis and toxic conjunctivitis, and those that affect the bulbar conjunctiva are typically cases of keratoconjunctivitis sicca.2,3,8


As part of the inflammatory cascade, blood vessels tend to become more permeable. This subsequently leads to leakage of serum, proteins, and inflammatory cells that create exudate. Grossly purulent exudate is seen mostly in hyperacute conjunctivitis, whereas a watery exudate is seen more often in viral conjunctivitis. The most common exudate is mucopurulent, a combination of both mucus and pus.1,3


Unlike most causes of acute conjunctivitis, the nature of the diseases that cause chronic conjunctivitis are not self-limiting. They include immunologic, traumatic, toxic, and neoplastic etiologies, as well as infectious causes. By accurately identifying the time course, conjunctival morphology, anatomic localization, and type of exudate, individual cases can be analyzed within a limited differential diagnosis, helping to facilitate successful diagnosis and straightforward initiation of a treatment plan.

1. Stern G. Chronic conjunctivitis part I. In: Stern GA, ed. Focal Points: clinical modules for ophthalmologists. San Francisco, CA: American Academy of Ophthalmology. 2012;30 (11):1-14.

2. Stern G. Chronic conjunctivitis part II. In: Stern GA, ed. Focal Points: clinical modules for ophthalmologists. San Francisco, CA: American Academy of Ophthalmology. 2012;30 (12):1-16.

3. Lindquist TD. Conjunctivitis: an overview and classification. In: Krachmer JH, Mannis MJ, Holland EJ, eds. Cornea. St. Louis: CV Mosby; 2011: 509-520.

4. Palioura S, Nikpoor N, Yoo S. Chronic conjunctivitis and warts. JAMA Ophthalmol. 2015;133(9):1083-1084.

5. Schuster V, Seregard S. Ligneous conjunctivitis. Surv Ophthalmol. 2003;48(4):369-388.

6. Dacosta J. Ocular cicatricial pemphigoid masquerading as chronic conjunctivitis: a case report. Clin Ophthalmol. 2012;6:2093-2095.

7. Srikumaran D, Akpek E. Mucous membrane pemphigoid: recent advances. Curr Opin Ophthalmol. 2012;23(6):523-527.

8. Bautista MA, Quan WD, Wang J. A case of chronic conjunctivitis following rituximab therapy. Adv Hematol. 2009;2009:272495.

Nicholas Colatrella, OD, FAAO, Dipl AAO, ABO, ABCMO
• adjunct professor of optometry, Illinois College of Optometry; medical director, PineCone Vision Center, Sartell, Minn.
• financial disclosure: honoraria, Allergan, BioDLogics, Bio-Tissue, Katena, Seed BioTech
• 320-258-3915; ncolatrella@pineconevisioncenter.com

Jeffrey R. Varanelli OD, FAAO, Dipl ABO, ABCMO
• director, optometric services, Simone Eye Center, Warren, Mich.
• financial disclosure: honoraria, Allergan, BioDLogics, Bio-Tissue, Johnson and Johnson, Katena, Seed BioTech, Shire
• 586-558-2981; secjrvod@gmail.com