What is the differential diagnosis for an 86-year-old male with a history of glaucoma, bilateral cataract surgery, and current symptoms of ocular watering, intermittent ocular redness, and 3+ keratic precipitates (KPs), with a past medical history of hypertension, hyperlipidemia, prostate cancer, benign prostatic hyperplasia (BPH), sleep apnea, and pleural plaque due to asbestos exposure?

Differential Diagnosis and Laboratory Testing for Anterior Uveitis with Keratic Precipitates

Primary Diagnosis

This patient has anterior uveitis with 3+ keratic precipitates, conjunctival injection, and ocular watering—the most critical immediate consideration is distinguishing between infectious (particularly viral) and non-infectious causes, as this fundamentally changes management and prognosis. 1, 2

Key Differential Diagnoses

Infectious Causes (Priority Given Clinical Presentation)

Cytomegalovirus (CMV) Anterior Uveitis

• Most likely viral etiology given unilateral or bilateral presentation with keratic precipitates, elevated IOP (18 mmHg bilaterally), and absence of posterior synechiae 3
• Classic features include mild anterior chamber inflammation, granulomatous KPs, elevated IOP, and iris atrophy—all present in this patient 3
• Geographic consideration: In Asian populations, CMV presents with diffuse stellate KPs; in European/Western populations, brown KPs located inferiorly are more common 3
• Absence of synechiae, macular edema, and retinitis supports CMV over other viral causes 3

Herpes Simplex Virus (HSV) Anterior Uveitis

• Consider if KPs extend beyond midline or if fresh pigmented KPs are present 2
• Typically unilateral with elevated IOP and sectoral iris atrophy 1
• Critical distinction: HSV more commonly causes corneal involvement and dendritic keratitis 1

Varicella Zoster Virus (VZV) Anterior Uveitis

• Less likely without history of dermatomal rash or pain 1
• Would expect more pronounced sectoral iris atrophy if present 1

Non-Infectious Causes

Medication-Induced Keratoconjunctivitis

• Highly relevant given patient's chronic use of multiple glaucoma medications (Simbrinza, Lumigan) 4
• Glaucoma medications are the most common cause of medication-induced conjunctivitis, especially with multiple medications and frequent dosing 4
• Presents with conjunctival injection, punctal edema, and inferior fornix follicles 4
• However, presence of 3+ KPs makes pure medication toxicity less likely as primary diagnosis 4

Sarcoidosis-Associated Uveitis

• Consider given patient's age and bilateral presentation 4
• Would expect granulomatous KPs, conjunctival nodules, and potential systemic involvement (lungs, lymph nodes) 4
• Bimodal age distribution with peak between 20-39 years makes this less likely in 86-year-old 4

Fuchs Uveitis Syndrome

• Chronic unilateral anterior uveitis with stellate KPs and iris atrophy 3
• CMV has been implicated in many cases of Fuchs syndrome, particularly in Asian populations 3
• Typically minimal inflammation with few symptoms 3

HLA-B27-Associated Anterior Uveitis

• Less likely given absence of acute pain, photophobia, and fibrinous reaction 1
• Patient lacks history of spondyloarthropathy 5

Other Considerations

Posner-Schlossman Syndrome (Glaucomatocyclitic Crisis)

• Recurrent hypertensive anterior uveitis with few granulomatous KPs 3
• Now recognized as CMV-associated in most cases 3
• IOP of 18 mmHg is not markedly elevated, making acute crisis less likely 3

Chronic Anterior Uveitis with Glaucoma Medication Confounding

• Presence of KPs, synechiae (if present), and bilateral disease predict reduced remission incidence 5
• Prior cataract surgery (>10 years ago) is associated with reduced remission incidence (aHR 0.70) 5

Essential Laboratory Testing

First-Line Aqueous Humor Analysis (Gold Standard)

Anterior Chamber Paracentesis for PCR Testing

• CMV PCR: Most critical test given clinical presentation 3
• HSV-1/HSV-2 PCR: Rule out herpes simplex 1
• VZV PCR: Rule out varicella zoster 1
• Toxoplasma PCR: If any posterior segment involvement develops 1

Serum Testing (Less Specific but Non-Invasive)

Viral Serology

• CMV IgG and IgM: Limited utility as most adults are seropositive; cannot distinguish active from latent infection 3
• HSV IgG and IgM: Similarly limited diagnostic value 1
• Note: Serology alone cannot confirm ocular CMV disease; aqueous PCR is required 3

Inflammatory/Autoimmune Markers

• ACE (Angiotensin-Converting Enzyme): Screen for sarcoidosis 4
• Lysozyme: Additional sarcoidosis marker 4
• ANA (Antinuclear Antibody): Screen for systemic autoimmune disease 4
• HLA-B27: If clinical suspicion for spondyloarthropathy 5
• Rheumatoid Factor: Given patient's age and potential for rheumatoid arthritis 4

Complete Blood Count with Differential

• Patient already has mildly elevated monocytes (1.13 K/uL) and low lymphocyte percent (15.9%) [@patient data@]
• Elevated monocytes may suggest chronic inflammation or infection 4
• Low lymphocytes could indicate immunosenescence in elderly or chronic viral infection 4

Imaging Studies

Chest X-ray or CT Chest

• Essential if sarcoidosis suspected to evaluate for hilar lymphadenopathy or pulmonary involvement 4
• Patient already has annual CT scans for pleural plaques; review most recent study [@patient data@]

Optical Coherence Tomography (OCT) of Macula

• Rule out cystoid macular edema, which would suggest more severe inflammation 3
• Baseline documentation for monitoring 3

Additional Ocular Testing

Corneal Endothelial Cell Count (Specular Microscopy)

• Critical for CMV anterior uveitis, which can cause corneal endotheliitis with reduced endothelial cell count 3
• Important given patient's age and prior cataract surgery 3

Gonioscopy

• Already performed; document any peripheral anterior synechiae or trabecular meshwork changes 4
• Important for glaucoma management given IOP of 18 mmHg on two medications 4

In Vivo Confocal Microscopy (IVCM) of KPs (if available)

• Can differentiate dendritiform/infiltrative KPs (non-granulomatous) from smooth-rounded/globular KPs (granulomatous) 2
• Helps distinguish infectious from non-infectious causes 2

Clinical Pitfalls and Caveats

Do Not Assume Medication Toxicity Alone

• While glaucoma medications can cause conjunctival injection, 3+ KPs indicate true anterior uveitis requiring different management 4, 2

Do Not Start Topical Corticosteroids Without Ruling Out Infection

• Corticosteroids may mask infection, enhance existing infection, and exacerbate viral infections (especially herpes simplex) 6
• Prolonged corticosteroid use causes glaucoma with optic nerve damage—particularly concerning in this patient already on two glaucoma medications 6

Do Not Rely on Serology Alone

• Aqueous humor PCR is required for definitive diagnosis of viral anterior uveitis 3
• Most adults are CMV seropositive; serology cannot distinguish active from latent infection 3

Monitor for Glaucoma Progression

• CMV anterior uveitis causes long-term glaucomatous optic neuropathy 3
• Patient's IOP of 18 mmHg on two medications requires close monitoring 4
• Structural optic nerve damage often precedes detectable visual field defects 7

Consider Age-Related Factors

• Older age (≥40 years) is associated with higher remission incidence in chronic anterior uveitis (aHR 1.29) 5
• However, presence of KPs predicts reduced remission (aHR 0.36) 5
• Prior cataract surgery predicts reduced remission (aHR 0.70) 5

Recommended Testing Algorithm

1. Immediate: Anterior chamber paracentesis for CMV, HSV, VZV PCR 3, 1
2. Same visit: Corneal endothelial cell count, OCT macula, detailed gonioscopy 3
3. Within 1 week: Serum ACE, lysozyme, ANA, HLA-B27, RF, review recent CBC 4
4. Within 2 weeks: Chest imaging if sarcoidosis suspected 4
5. Ongoing: Close IOP monitoring and visual field testing given glaucoma risk 4, 7