Conjunctivitis Differential Diagnosis: A Comprehensive Guide for Clinicians

Conjunctivitis, commonly known as pink eye, is a prevalent condition characterized by inflammation of the conjunctiva, the transparent membrane covering the white part of the eye and the inner surface of the eyelids. As a leading cause of red eye complaints in primary care and emergency settings, conjunctivitis presents a significant healthcare burden. While often benign and self-limiting, accurately diagnosing conjunctivitis is crucial to differentiate it from more serious, vision-threatening conditions. This article provides an in-depth guide to the differential diagnosis of conjunctivitis, equipping clinicians with the knowledge to effectively evaluate and manage patients presenting with red eye.

Understanding Conjunctivitis: Types and Etiology

Conjunctivitis is broadly classified based on its etiology and duration. Etiologically, it can be infectious or non-infectious. Infectious conjunctivitis is primarily caused by viruses, bacteria, and less commonly, fungi or parasites. Non-infectious causes include allergies, toxins, and irritants. In terms of duration, conjunctivitis is categorized as acute (lasting less than 4 weeks) or chronic (lasting more than 4 weeks). Viral conjunctivitis is the most common infectious type, with adenovirus being the predominant pathogen. Bacterial conjunctivitis follows in prevalence, particularly in children. Allergic conjunctivitis is the most frequent non-infectious form.

Accurate diagnosis necessitates a comprehensive understanding of the various etiologies and their characteristic presentations. While conjunctivitis is often straightforward, its symptoms can overlap with those of more serious ocular conditions, making differential diagnosis paramount.

Clinical Presentation: Key Features and Symptoms

Patients with conjunctivitis typically present with a constellation of symptoms, including eye redness, discharge, discomfort, and sometimes visual disturbances. However, these symptoms are not exclusive to conjunctivitis and can be indicative of other ocular pathologies. Key signs and symptoms to consider include:

• Redness (Hyperemia): Diffuse redness affecting both bulbar and tarsal conjunctiva is characteristic of conjunctivitis. Localized redness may suggest other conditions.
• Discharge: The nature of discharge varies depending on the cause. Watery discharge is common in viral and allergic conjunctivitis, while purulent or mucopurulent discharge is more suggestive of bacterial infection. Hyperpurulent discharge is a hallmark of gonococcal conjunctivitis.
• Itching: Intense itching is a hallmark of allergic conjunctivitis, although it can also be present in other types.
• Pain: While conjunctivitis is typically associated with discomfort or a gritty sensation, significant eye pain is atypical and should raise suspicion for other diagnoses.
• Visual Acuity: Vision is usually unaffected in simple conjunctivitis. Blurred vision warrants further investigation.
• Photophobia: Mild photophobia can occur in viral conjunctivitis, but severe photophobia is more common in keratitis or iritis.
• Foreign Body Sensation: This is a common complaint in various ocular surface disorders, including conjunctivitis, dry eye, and corneal abrasions.
• Lymphadenopathy: Preauricular lymph node involvement is often associated with viral conjunctivitis.
• Follicles and Papillae: Follicles (small, elevated lesions) are commonly seen in viral and chlamydial conjunctivitis, while papillae (small elevations with central vessels) are less specific and can be present in bacterial, allergic, and other types.

Differentiating conjunctivitis from other causes of red eye relies heavily on careful evaluation of these clinical features, coupled with a detailed patient history.

The Crucial Role of Differential Diagnosis

The primary goal in evaluating a patient with red eye is to differentiate benign conjunctivitis from serious conditions that can lead to vision loss. Misdiagnosis or delayed diagnosis of conditions like keratitis, iritis, or acute glaucoma can have severe consequences. Therefore, a systematic approach to differential diagnosis is essential.

Key reasons why differential diagnosis is critical in conjunctivitis:

• To Rule Out Vision-Threatening Conditions: Several conditions presenting with red eye, such as acute angle-closure glaucoma, infectious keratitis, and scleritis, require urgent ophthalmologic intervention to prevent irreversible vision loss.
• To Guide Appropriate Management: The treatment for conjunctivitis varies significantly depending on the underlying cause. For example, bacterial conjunctivitis may warrant antibiotics, while viral conjunctivitis is typically self-limiting and requires symptomatic treatment. Allergic conjunctivitis necessitates allergen avoidance and anti-allergy medications. Incorrect treatment can be ineffective or even harmful.
• To Prevent Complications: Certain types of conjunctivitis, such as herpes simplex conjunctivitis or gonococcal conjunctivitis, can lead to serious complications if not promptly and appropriately managed. Differential diagnosis helps identify these high-risk cases.
• To Reduce Unnecessary Antibiotic Use: Over-prescription of antibiotics for viral conjunctivitis contributes to antibiotic resistance. Accurate differentiation helps limit antibiotic use to cases of bacterial conjunctivitis.
• To Alleviate Patient Anxiety: Red eye can be alarming for patients. A clear diagnosis and explanation of the condition, along with reassurance when appropriate, can significantly reduce patient anxiety.

Differential Diagnosis of Conjunctivitis: A Step-by-Step Approach

The differential diagnosis of conjunctivitis can be approached by categorizing conditions based on their urgency: emergent (vision-threatening) and non-emergent.

Emergent Conditions Mimicking Conjunctivitis

These conditions require prompt recognition and referral to an ophthalmologist.

1. Acute Angle-Closure Glaucoma: This is an ophthalmic emergency characterized by a sudden increase in intraocular pressure (IOP).

   • Differentiating Features:
     • Severe Eye Pain: Intense, throbbing pain, often radiating to the forehead or brow.
     • Blurred Vision or Halos: Significant vision reduction and seeing halos around lights.
     • Nausea and Vomiting: Systemic symptoms may accompany severe pain.
     • Pupil: Mid-dilated and non-reactive pupil.
     • Cornea: Steamy or hazy cornea.
     • Elevated IOP: Tonometry will reveal markedly elevated IOP.
     • Localized Redness: Circumcorneal redness (ciliary flush) sparing the tarsal conjunctiva.
     • Absence of Discharge: Typically no discharge.

2. Keratitis (Corneal Inflammation): Inflammation of the cornea, often infectious but can be non-infectious.

   • Differentiating Features:

     • Moderate to Severe Eye Pain: Pain is often more significant than in conjunctivitis.
     • Photophobia: Marked sensitivity to light.
     • Blurred Vision: Vision may be affected, especially if central cornea is involved.
     • Foreign Body Sensation: Patients often describe a gritty or scratching sensation.
     • Localized Redness: Ciliary flush is common.
     • Corneal Opacity or Infiltrate: Visible corneal lesion or haze on examination, especially with fluorescein staining.
     • Pupil: Pupil is typically normal, but may be constricted in response to pain.
     • Discharge: May have watery or mucopurulent discharge, but less prominent than in conjunctivitis.

   • Types of Keratitis to Consider in Differential Diagnosis:

     • Bacterial Keratitis: Often associated with contact lens wear, trauma, or corneal surface disease. Rapid onset, purulent discharge, corneal infiltrate.
     • Viral Keratitis (Herpes Simplex Keratitis): May present with dendritic corneal ulcers, decreased corneal sensation.
     • Fungal Keratitis: More insidious onset, often associated with vegetable matter trauma or chronic steroid use. Feathery infiltrates.
     • Acanthamoeba Keratitis: Severe pain out of proportion to clinical findings, associated with contact lens wear and tap water exposure. Ring infiltrate.

3. Iritis (Anterior Uveitis): Inflammation of the iris and anterior chamber.

   • Differentiating Features:
     • Moderate to Severe Eye Pain: Dull, aching pain, often worse with accommodation (reading).
     • Photophobia: Significant light sensitivity.
     • Blurred Vision: Vision may be reduced.
     • Ciliary Flush: Circumcorneal redness.
     • Constricted Pupil: Pupil is often smaller than normal and may be irregular.
     • Sluggish Pupillary Response: Pupil reacts poorly to light.
     • Hypopyon: Layer of white blood cells in the anterior chamber (may be present but not always).
     • No Discharge: Typically no significant discharge.

4. Scleritis: Inflammation of the sclera (white part of the eye).

   • Differentiating Features:
     • Severe, Deep Eye Pain: Excruciating pain that may radiate to the face, jaw, or head. Often described as boring or aching and worsens at night and in the early morning.
     • Pain with Eye Movement: Pain exacerbated by extraocular movements.
     • Tenderness to Palpation: Exquisite tenderness to touch over the sclera.
     • Vision Loss: May occur in severe cases.
     • Photophobia: Present.
     • Scleral Edema and Injection: Deep, violaceous or bluish-red scleral injection, often nodular or diffuse.
     • No Discharge: Typically no discharge.
     • Association with Systemic Diseases: Scleritis is often associated with systemic autoimmune diseases like rheumatoid arthritis, lupus, and vasculitis.

5. Corneal Ulcer: Erosion of the corneal epithelium extending into the stroma.

   • Differentiating Features:
     • Moderate to Severe Pain: Significant pain and foreign body sensation.
     • Photophobia: Marked light sensitivity.
     • Blurred Vision: Vision may be affected depending on ulcer location and size.
     • Corneal Defect: Visible corneal defect, readily apparent with fluorescein staining.
     • Purulent Discharge: May have purulent discharge.
     • Localized or Diffuse Redness: Can have ciliary flush or more diffuse redness.
     • History of Trauma or Contact Lens Wear: Often associated with these factors.

6. Corneal Abrasion: Superficial scratch or injury to the corneal epithelium.

   • Differentiating Features:
     • Sudden Onset of Severe Pain: Sharp, intense pain immediately following injury.
     • Foreign Body Sensation: Prominent gritty feeling.
     • Tearing: Excessive tearing.
     • Photophobia: Light sensitivity.
     • Fluorescein Staining: Linear or irregular corneal epithelial defect visible with fluorescein.
     • History of Trauma: Usually a clear history of recent eye trauma (e.g., finger scratch, foreign body).

7. Corneal Foreign Body: Presence of a foreign object on or embedded in the cornea.

   • Differentiating Features:
     • Foreign Body Sensation: Persistent feeling of something in the eye.
     • Tearing and Reflex Blinking: Increased tearing and blinking.
     • Localized Redness: Redness may be localized around the foreign body.
     • Visible Foreign Body: Foreign body may be visible on slit lamp examination or even with the naked eye.
     • Fluorescein Staining: May show corneal abrasion around the foreign body.
     • History of Exposure: History of working with machinery, dust, or other environments with potential foreign bodies.

8. Traumatic Hyphema: Bleeding into the anterior chamber of the eye, usually due to trauma.

   • Differentiating Features:
     • History of Eye Trauma: Recent blunt or penetrating eye injury.
     • Visible Blood in Anterior Chamber: Layer of red blood cells visible in the anterior chamber, often layering inferiorly.
     • Eye Pain: Pain may be present.
     • Blurred Vision: Vision is often reduced.
     • Elevated IOP: IOP may be elevated.

Non-Emergent Conditions Mimicking Conjunctivitis

These conditions are less immediately sight-threatening but still require accurate diagnosis and management.

1. Episcleritis: Inflammation of the episclera, the tissue layer superficial to the sclera.

   • Differentiating Features:
     • Localized Redness: Sectoral redness, often bright red or salmon-pink. Can be nodular or diffuse.
     • Mild Discomfort: Mild aching or discomfort, less severe than scleritis.
     • No Pain with Eye Movement: Unlike scleritis, pain is not exacerbated by eye movement.
     • No Tenderness to Palpation: No significant tenderness to touch.
     • Vision is Usually Normal: Visual acuity is typically unaffected.
     • Phenylephrine Blanching: Episcleral vessels will blanch with topical 2.5% phenylephrine, while scleral vessels will not.
     • Self-Limiting: Often resolves spontaneously within a few weeks.

2. Pterygium: Fleshy, triangular growth of conjunctival tissue onto the cornea.

   • Differentiating Features:
     • Localized Redness: Redness is typically localized to the pterygium itself.
     • Visible Growth: Characteristic fleshy growth extending onto the cornea, usually from the nasal side.
     • Asymptomatic or Mild Irritation: Often asymptomatic or causes mild irritation, dryness, or foreign body sensation.
     • Chronic Condition: Develops slowly over time.

3. Blepharitis: Inflammation of the eyelids.

   • Differentiating Features:
     • Eyelid Symptoms Predominate: Itching, burning, and irritation of the eyelids are more prominent than conjunctival symptoms.
     • Eyelid Margin Changes: Redness, swelling, crusting, and scaling of the eyelid margins.
     • Lash Changes: Loss of eyelashes (madarosis), misdirected eyelashes (trichiasis).
     • Foreign Body Sensation: May have gritty sensation.
     • Mild Conjunctival Redness: Conjunctival injection may be present, but often less diffuse than in conjunctivitis.
     • Recurrent or Chronic: Blepharitis is often a chronic and relapsing condition.

4. Hordeolum (Stye): Acute infection of an eyelid gland (usually sebaceous gland of Zeis or sweat gland of Moll).

   • Differentiating Features:
     • Localized Eyelid Swelling and Redness: Tender, localized bump or swelling on the eyelid.
     • Pain and Tenderness: Painful to touch.
     • No Significant Conjunctival Involvement: Conjunctival redness may be minimal and localized near the hordeolum.
     • Eyelid Margin Focus: Lesion is centered on the eyelid margin.

5. Chalazion: Chronic, non-infectious inflammation of a meibomian gland in the eyelid.

   • Differentiating Features:
     • Painless Eyelid Nodule: Painless lump or nodule in the eyelid.
     • Minimal Redness: Little or no redness of the eyelid or conjunctiva.
     • Chronic Condition: Develops gradually and persists.
     • May Follow Hordeolum: Can develop after a hordeolum resolves.

6. Dry Eye Disease (Keratoconjunctivitis Sicca): Chronic condition characterized by insufficient tear production or poor tear quality.

   • Differentiating Features:
     • Dryness Symptoms Predominate: Burning, stinging, dryness, gritty sensation, paradoxically, sometimes excessive tearing.
     • Fluctuating Vision: Vision may fluctuate throughout the day, often worse later in the day.
     • Lack of Discharge: Typically no significant discharge, or watery discharge.
     • Conjunctival Redness: May have mild conjunctival injection, but often less pronounced than in conjunctivitis.
     • Punctate Epithelial Erosions (PEE): Visible on fluorescein staining.
     • History of Systemic Conditions or Medications: Associated with autoimmune diseases (Sjögren’s syndrome), hormonal changes, and certain medications.

7. Subconjunctival Hemorrhage: Rupture of small blood vessels beneath the conjunctiva, causing blood to pool between the conjunctiva and sclera.

   • Differentiating Features:
     • Sudden Onset of Bright Red Patch: Abrupt appearance of a sharply demarcated, bright red area on the white of the eye.
     • No Pain or Minimal Irritation: Usually painless or minimally irritating.
     • No Discharge: No discharge.
     • Normal Vision: Vision is unaffected.
     • History of Coughing, Straining, Trauma, or Spontaneous: May be associated with these triggers, or can be spontaneous.
     • Blood Confined to Subconjunctival Space: Blood is located beneath the conjunctiva and does not extend onto the cornea.

8. Contact Lens Overwear: Inflammation and irritation due to prolonged or improper contact lens wear.

   • Differentiating Features:
     • History of Contact Lens Wear: Recent extended contact lens wear or improper lens hygiene.
     • Discomfort Worsens with Lens Wear: Symptoms are exacerbated by contact lens use and improve with lens removal.
     • Corneal Findings: May have corneal edema, punctate epithelial erosions, or corneal neovascularization in chronic cases.
     • Mild Conjunctival Redness: Conjunctival injection may be present.

9. Allergic Conjunctivitis: Inflammation of the conjunctiva due to an allergic reaction.

   • Differentiating Features:
     • Intense Itching: Primary symptom is often severe itching.
     • Watery Discharge: Watery or stringy discharge.
     • Chemosis: Conjunctival swelling.
     • Bilateral Involvement: Typically affects both eyes.
     • Seasonal Pattern: Often seasonal, associated with pollen or other airborne allergens.
     • History of Allergies or Atopy: Personal or family history of allergies, asthma, or eczema.
     • Papillae: Conjunctival papillae are common, especially on the tarsal conjunctiva.
     • No Follicles: Follicles are typically absent.

Diagnostic Evaluation for Differential Diagnosis

While clinical examination is often sufficient for diagnosing simple conjunctivitis, certain situations warrant further diagnostic testing to aid in differential diagnosis and confirm the etiology.

• Visual Acuity Testing: Always assess visual acuity to rule out vision-threatening conditions.
• Pupillary Examination: Evaluate pupil size, shape, and reactivity to light. Unequal or poorly reactive pupils suggest conditions other than simple conjunctivitis.
• Intraocular Pressure (IOP) Measurement: Tonometry is crucial to rule out acute angle-closure glaucoma in patients with pain, blurred vision, or suspicious findings.
• Slit Lamp Biomicroscopy: Essential for detailed examination of the conjunctiva, cornea, iris, and anterior chamber. Allows for visualization of corneal lesions, anterior chamber cells and flare, hypopyon, and other subtle findings.
• Fluorescein Staining: Highlights corneal epithelial defects, such as abrasions, ulcers, and dendritic lesions of herpes keratitis.
• Eyelid Eversion: Examine the tarsal conjunctiva for follicles, papillae, and foreign bodies.
• Preauricular Lymph Node Examination: Palpate for preauricular lymphadenopathy, which is suggestive of viral conjunctivitis.
• Conjunctival Scrapings and Cultures: Reserved for specific situations:
  • Severe Purulent Discharge: To rule out gonococcal or chlamydial conjunctivitis.
  • Neonatal Conjunctivitis: To identify the causative organism and guide treatment.
  • Treatment-Resistant Conjunctivitis: To identify unusual pathogens or antibiotic resistance.
  • Recurrent Conjunctivitis: To investigate underlying causes.
  • Giemsa Stain: To detect chlamydial inclusions.
  • Gram Stain and Bacterial Culture: To identify bacterial pathogens.
  • Viral Culture or PCR: To confirm viral etiology, particularly adenovirus or herpes simplex virus (less commonly performed in routine practice).
• Rapid Antigen Tests for Adenovirus: Commercially available point-of-care tests for adenovirus can help confirm viral conjunctivitis and reduce unnecessary antibiotic prescriptions.
• Allergy Testing: Skin prick tests or serum IgE testing may be considered in cases of suspected allergic conjunctivitis, especially if seasonal or perennial allergic conjunctivitis is suspected and allergen identification is desired.
• Imaging Studies: Rarely indicated for routine conjunctivitis. May be considered in cases with suspected orbital cellulitis or cavernous sinus thrombosis.

Management Strategies Based on Differential Diagnosis

Appropriate management of red eye depends entirely on accurate differential diagnosis.

• Conjunctivitis (Viral, Bacterial, Allergic): Management is tailored to the specific type of conjunctivitis, ranging from symptomatic relief with artificial tears and cool compresses to topical antibiotics or anti-allergy medications.
• Emergent Conditions (Glaucoma, Keratitis, Iritis, Scleritis, Corneal Ulcer): Require immediate ophthalmologic referral and specialized management, often including topical or systemic medications, laser treatment, or surgery.
• Non-Emergent Conditions (Episcleritis, Pterygium, Blepharitis, Dry Eye): Managed according to the specific diagnosis, with treatments ranging from topical lubricants and anti-inflammatories to eyelid hygiene measures.

Conclusion

Conjunctivitis is a common and often benign condition, but its differential diagnosis is crucial to identify and manage potentially sight-threatening ocular diseases. A thorough history, careful clinical examination, and selective use of diagnostic testing are essential for accurate differentiation. Clinicians must be vigilant in recognizing red eye presentations that deviate from typical conjunctivitis and warrant prompt ophthalmologic referral. By mastering the differential diagnosis of conjunctivitis, healthcare professionals can ensure optimal patient care, prevent vision loss, and promote appropriate and targeted management strategies.

This comprehensive guide serves as a valuable resource for clinicians to enhance their understanding of Conjunctivitis Differential Diagnosis, ultimately improving patient outcomes and reducing the burden of red eye complaints in clinical practice.