What are the possible causes and recommended management for a gray‑tinted peripheral sclera?

Gray-Tinted Peripheral Sclera: Causes and Management

Primary Differential Diagnosis

The most critical consideration for gray-tinted peripheral sclera is scleral thinning, which requires urgent evaluation to prevent potential perforation and vision loss. 1

Life-Threatening and Vision-Threatening Causes

• Necrotizing scleritis presents with muddy or discolored scleral appearance and represents a medical emergency requiring immediate ophthalmology consultation, as it can rapidly destroy scleral structural components and lead to perforation 2, 3
• Surgically-induced necrotizing scleritis occurs in approximately 1 in 4,000 cases following strabismus or other ocular surgery, is more common in adults, and manifests as progressive scleral thinning with gray discoloration 4
• Scleral thinning from any cause allows visualization of underlying uveal tissue, creating a gray, blue, or slate-colored appearance where the dark choroid shows through the attenuated sclera 1, 5

Medication-Induced Causes

• Chlorpromazine-induced ocular pigmentation can cause slate-gray discoloration of exposed ocular tissues, typically occurring after prolonged use (2+ years) at dosages of 300 mg daily or higher, with pigment deposition in both the cornea and sclera 6
• Hydroquinone-containing skin-lightening creams cause exogenous ochronosis with black-blue pigmentation, scleral thinning, and plaques—this presents with a characteristic triad of posterior corneal striae, scleral thinning/plaques, and linear brown epithelial pigmentation in the lower cornea 5

Congenital and Degenerative Causes

• Oculodermal melanocytosis (ODM) presents with hyperpigmentation of the sclera, conjunctiva, and other ocular structures, predominantly affecting Asian females, and carries increased risk for glaucoma and uveal melanoma 7
• Post-surgical or post-traumatic scleral thinning creates areas where the underlying uveal pigment becomes visible, appearing as gray or dark patches 4, 1

Diagnostic Approach

Essential Examination Components

• Slit-lamp biomicroscopy using sclerotic scatter, specular reflection, and indirect illumination to identify scleral thinning, document areas of thinning, and assess for associated inflammation 8
• Indirect ophthalmoscopy to evaluate the extent of scleral involvement and rule out posterior segment complications 9
• Intraocular pressure measurement to screen for glaucoma, particularly in cases of ODM or inflammatory scleritis 2, 7
• Gonioscopy before dilation when neovascularization is suspected or IOP is elevated, as angle abnormalities can occur with ODM 9, 7

Advanced Imaging When Indicated

• B-scan ultrasonography if media opacity precludes adequate examination or to assess posterior scleral involvement 9, 8
• Optical coherence tomography (OCT) can help characterize scleral thickness and detect associated retinal pathology 9

Critical History Elements

• Medication history: Specifically inquire about phenothiazines (chlorpromazine), corticosteroids, and topical skin-lightening products containing hydroquinone 6, 5
• Surgical history: Previous strabismus surgery, glaucoma surgery, or other ocular procedures increase risk for surgically-induced necrotizing scleritis 4
• Systemic disease: Screen for rheumatoid arthritis and other autoimmune conditions associated with scleritis 2, 3
• Ethnic background: ODM predominantly affects Asian populations; exogenous ochronosis from hydroquinone affects individuals of West African origin 7, 5

Management Algorithm

Immediate Actions for Inflammatory/Necrotizing Scleritis

If necrotizing scleritis is suspected (muddy/discolored sclera with inflammation), initiate immediate systemic corticosteroids plus disease-modifying anti-rheumatic drugs (DMARDs), with high-dose oral prednisone (1 mg/kg/day) or IV methylprednisolone for severe cases. 2

• Concurrent initiation of steroid-sparing immunomodulatory therapy such as methotrexate, mycophenolate mofetil, or azathioprine is required 2
• Anti-TNF agents (infliximab 5 mg/kg IV at weeks 0,2,6, then every 8 weeks, or adalimumab 40 mg subcutaneously every 2 weeks) are indicated when conventional DMARDs fail 2
• Close coordination between ophthalmology and rheumatology is mandatory, with follow-up every 1-2 weeks during acute phase 2

Non-Inflammatory Scleral Thinning

• Conservative management includes monitoring for progression and avoiding trauma to the affected area 1
• Surgical reinforcement options include scleral transplantation, amniotic membrane transplantation, conjunctival flaps, or alternative biological grafts when thinning is severe or progressive 1

Medication-Related Pigmentation

• Discontinue offending agent: Stop chlorpromazine or hydroquinone-containing products immediately 6, 5
• Monitor for regression: Chlorpromazine-induced pigmentation may fade following discontinuation, though this is not guaranteed 6
• Long-term surveillance: Patients on chlorpromazine requiring continued therapy should have periodic ocular examinations 6

Oculodermal Melanocytosis

• Routine ophthalmological monitoring for glaucoma development and malignant transformation to uveal melanoma 7
• Careful iris examination for mammillations (dome-shaped protuberances), which indicate higher risk of malignant transformation 7

Critical Pitfalls to Avoid

• Do not delay ophthalmology referral when gray scleral discoloration is accompanied by pain, redness, or vision changes—this may represent necrotizing scleritis requiring emergency treatment 2
• Do not assume benign etiology without thorough examination, as scleral thinning can progress to perforation 1
• Do not overlook medication history, particularly in patients using skin-lightening products or long-term psychotropic medications 6, 5
• Do not perform dilation before gonioscopy when neovascularization is suspected, as this can obscure angle assessment 9