What are the differential diagnoses and appropriate management for a white lesion on the eye?

White Lesion in the Eye: Differential Diagnosis and Management

A white lesion on the eye requires immediate systematic evaluation to distinguish between benign conditions, inflammatory disorders, infectious etiologies, and potentially life-threatening malignancies, with management ranging from observation to urgent systemic immunosuppression or oncologic referral depending on the specific diagnosis.

Critical Initial Assessment

Location-Based Differential Diagnosis

Conjunctival white lesions:

• Ocular surface squamous neoplasia presents as conjunctival hyperemia with papillomatous or sessile nodules that may be leukoplakic or gelatinous, associated with HPV infection and significant UV exposure 1
• Sebaceous carcinoma appears as a hard nodular, nonmobile mass with yellowish discoloration, often mimicking chronic unresponsive blepharoconjunctivitis 1
• Conjunctival lymphoma manifests as a painless, pink-to-white "salmon patch" fleshy swelling, most commonly on superior or inferior conjunctiva 1
• Amelanotic melanoma can present as a white-pink lesion on bulbar or palpebral conjunctiva, with enlargement and vascular thickening 1

Intraocular white lesions:

• Retinoblastoma shows white retinal masses with potential vitreous seeding and retinal detachment 1
• White dot syndromes including multifocal choroiditis present as yellow-white punched-out round spots deep to the retina 1
• Vitelliform lesions appear as yellow-white subretinal material with characteristic hyperautofluorescence on fundus autofluorescence imaging 1
• Melanocytoma of the optic disc can have a white plaque over the surface indicating fibrous metaplasia of overlying retinal pigment epithelium 1, 2

Diagnostic Workup Algorithm

Step 1: Determine Anatomic Location

• Examine whether the lesion is on the conjunctival surface, within the iris/ciliary body, or in the posterior segment 1
• Document laterality (unilateral vs bilateral), as bilateral presentation suggests inflammatory or hereditary conditions 1, 3

Step 2: Multimodal Imaging (for intraocular lesions)

• Optical coherence tomography (OCT) identifies subretinal fluid, outer retinal disruption, and lesion depth 4, 3
• Fluorescein angiography (FA) demonstrates focal leakage points and neovascularization 4, 3
• Indocyanine green angiography (ICGA) shows hypofluorescent changes characteristic of choroidal pathology 4, 3
• OCT-angiography excludes neovascular networks and differentiates pachychoroid neovasculopathy 4, 3
• Fundus autofluorescence (FAF) characterizes inflammatory versus degenerative processes 4, 3

Step 3: Rule Out Masqueraders

Common pitfall: Widespread grayish-white outer retinal spots with hyperautofluorescence are NOT pathognomonic for benign white dot syndromes 5

Critical masqueraders requiring urgent workup:

• Syphilis - obtain RPR/VDRL and treponemal antibody testing 5
• Lymphoma - consider systemic evaluation and biopsy 5
• Tuberculosis - obtain QuantiFERON-TB Gold or PPD 5
• Sarcoidosis - check ACE level, chest imaging, and consider biopsy 6, 5
• Candidal endophthalmitis - classic 3-dimensional white retinal lesions with vitreal extension in candidemic patients 7

Management by Diagnosis

Neoplastic Lesions (Conjunctival)

Ocular surface squamous neoplasia:

• Surgical excision with assessment of invasion into episclera or corneal stroma 1
• Document tumor at all resection margins including deep and lateral margins 1
• Consider topical chemotherapy or immunotherapy for extensive disease 1

Sebaceous carcinoma:

• Urgent referral to ocular oncology given risk of orbital invasion and metastases 1
• Multiple biopsies may be needed as it often mimics chronic blepharoconjunctivitis 1

Amelanotic melanoma:

• Immediate referral to ocular oncology for staging and treatment planning 1
• Document thickness in millimeters and assess for invasion into underlying tissues 1

Inflammatory White Lesions (Choroiditis/White Dot Syndromes)

For multifocal choroiditis with panuveitis:

• Systemic corticosteroids combined with immunosuppressive agents - NEVER corticosteroids as monotherapy 4, 3
• Start high-dose oral prednisolone at 1 mg/kg/day (maximum 60 mg/day) immediately without waiting for complete diagnostic workup 4, 6
• Add steroid-sparing immunosuppressive therapy early: mycophenolate mofetil, azathioprine, or methotrexate 4, 6
• Regular ophthalmologic surveillance for at least 3 years after achieving remission 4, 3

For central serous chorioretinopathy with single focal leak:

• Observation is recommended for the first 4 months given high rate of spontaneous resolution 4
• Half-dose photodynamic therapy indicated if rapid visual recovery needed, recurrent episode, or bilateral disease 4

Infectious White Lesions

Candidal endophthalmitis:

• Classic 3-dimensional white retinal lesions with vitreal extension are virtually diagnostic 7
• Initiate systemic antifungal therapy immediately 7
• Serial ophthalmoscopic examinations to monitor response (lesions resolve in mean of 33 days) 7

Syphilitic chorioretinitis:

• High-dose intravenous penicillin G per CDC guidelines 5
• Outer retinal lesions and imaging findings resolve with treatment 5

Retinoblastoma (Pediatric Emergency)

Immediate enucleation or globe-sparing therapy based on:

• Number and size of lesions 1
• Presence of vitreous seeding 1
• Evidence of choroidal invasion or extraocular extension 1
• Optic nerve involvement (prelaminar, laminar, retrolaminar, or to resection margin) 1

Common Pitfalls to Avoid

1. Do not assume all white lesions are benign - sebaceous carcinoma and amelanotic melanoma can masquerade as chronic inflammation 1

2. Do not use corticosteroids as monotherapy for inflammatory choroiditis - always combine with immunosuppressive agents 4, 3

3. Do not dismiss nonspecific retinal findings in bacteremic/candidemic patients - cotton wool spots and retinal hemorrhages occur in 11-20% but are often due to underlying systemic disease rather than infection 7

4. Do not delay systemic workup for inflammatory white lesions - syphilis, tuberculosis, sarcoidosis, and lymphoma require specific systemic treatment 6, 5

5. Do not rely on fundoscopy alone - multimodal imaging is essential to characterize lesion depth, activity, and associated complications 4, 3, 8