Ophthalmological manifestations in autoimmune diseases: Overcoming diagnostic and therapeutic challenges

Table 1 Frequently encountered ocular diseases and manifestations associated with autoimmune diseases, their clinical symptoms, their differential diagnoses, and the most common complications

Condition/manifestation	Primary location	Clinical features	Common autoimmune diseases	Non-autoimmune/differential diagnoses	Complications	Ref.
Uveitis	Uvea (iris, ciliary body, choroid)	Redness, pain, photophobia, blurred vision, floaters	RA, SS, BD, CD, UC, MS, celiac, sarcoidosis	HSV, VZV, CMV, toxoplasmosis, TB, trauma, leukemia, Lyme disease	Macular edema, glaucoma, cataracts, Horner’s syndrome	[7,9,12-27,60-63]
Keratitis	Cornea	Redness, photophobia, blurred vision, pain, FB sensation	RA, SS, SLE, celiac, Hashimoto’s, vasculitis	HSV, HHV-6, fungi, bacteria, trichiasis, trauma	Ulceration, perforation, corneal thickening	[9,17,21,30-38,61,62,64]
Optic neuritis	Optic nerve	Visual impairment (unilateral or bilateral), pain with eye movement	MS, NMO, MOG-AD, sarcoidosis, SLE, SS	Syphilis, TB, Lyme disease, compressive lesions, toxins	Blindness, demyelination, optic atrophy	[40-42,46-53,65]
Episcleritis	Episcleral tissue	Mild pain, redness, irritation	RA, SS, CD, UC, dermatomyositis	Syphilis, Lyme disease, TB, HZV, hypersensitivity reactions	Generally self-limiting	[16,54,56,66-70]
Scleritis	Sclera	Severe pain, photophobia, possible vision loss	RA, SS, CD, UC, GPA, PAN, BD	Monkeypox, TB, HZV, syphilis, post-op, bisphosphonates	Necrotizing inflammation, retinal vasculitis, vision loss	[10,16,54-59,62,66,67,71]
Keratoconjunctivitis sicca	Cornea/Conjunctiva	Dryness, photophobia, gritty sensation	RA, SS, CD, celiac, GBS, MG, GD, Hashimoto’s, psoriasis, SSc	Medications, meibomian gland dysfunction, environment, HIV/AIDS	Corneal damage, infection risk	[72,73]
Conjunctivitis	Conjunctiva	Redness, edema, lacrimation, discomfort	RA, CD, psoriasis, celiac	Allergens, irritants, viruses (e.g., SARS-CoV-2, flavivirus)	Persistent inflammation, scarring	[61,62,74,75]
Blepharitis	Eyelids	Burning, photophobia, irritation, redness	RA, CD, MG, psoriasis	Staph, VZV, meibomian dysfunction, rosacea	Chronic discomfort, eyelid scarring	[76,77]
Retinal vasculitis	Retina	Floaters, scotoma, color vision changes	RA, SS, BD, CD	CMV, TB, syphilis, Lyme disease, flavivirus	Vision loss, retinal ischemia	[60,61,78]
Macular edema	Macula	Blurry vision, micro/macropsia, color impairment	RA, BD, GBS, DM1	RVO, tumors, trauma, radiation	Vision loss, distortion	[79,80]
Choroiditis	Choroid	Floaters, metamorphopsia, central vision loss	RA	TB, vector-borne infections	Vision distortion, scarring	[60,81]
Photophobia	Nonspecific	Light intolerance	SS, GBS, Hashimoto’s	Migraine, TBI, optic/chiasmal pathology	Underlying diagnosis-dependent	[82,83]
Retinal detachment	Retina	Flashes, floaters, shadow over vision	RA, BD, UC, MS, SSc	Trauma, tumors, medications	Vision loss	[84]
Vitreal/retinal hemorrhage	Vitreous/retina	Floaters, cobwebs, haziness	BD, MS, GBS, dermatomyositis	Endocarditis, trauma, PCV, flavivirus	Vision loss	[62,72,77,85]
Retinal vein occlusion	Retina	Vision loss, RAPD	BD, UC, celiac, dermatomyositis	Polycythemia vera, thrombophilia, drugs	Edema, hemorrhage, ischemia	[86]
Glaucoma	Optic nerve	Progressive vision loss, dark adaptation delay	BD, MS, GD, DM1	Ocular HTN, steroids, surgery, trauma	Irreversible blindness	[87]
Corneal ulcers	Cornea	Pain, redness, photophobia, discharge	SS, CD, celiac	Bacteria, HHV-6, trauma	Vision loss, perforation	[71,72]
Diplopia	EOMs/CNS	Double vision	GBS, MG, GD, Hashimoto’s, SSc, dermatomyositis	Orbital mass, refractive error, neuromuscular issues	Falls, impaired depth perception	[88,89]
Optic atrophy	Optic nerve	Vision loss, field defects	BD	Ischemic, infectious, compressive, toxic	Permanent vision loss	[65]
Cataracts	Lens	Blurry vision, glare, color desaturation	CD, Celiac, MS, DM1, psoriasis, SSc, dermatomyositis	Corticosteroids, trauma, radiation	Progressive vision loss	[90]

RA: Rheumatoid arthritis; SS: Sjögren’s syndrome; BD: Behçet’s disease; CD: Crohn’s disease; UC: Ulcerative colitis; MS: Multiple sclerosis; SLE: Systemic lupus erythematosus; NMO: Neuromyelitis optica; MOG-AD: Myelin oligodendrocyte glycoprotein antibody-associated disease; GPA: Granulomatosis with polyangiitis; PAN: Polyarteritis nodosa; GBS: Guillain–Barré syndrome; MG: Myasthenia gravis; GD: Gaucher disease; SSc: Systemic sclerosis; DM1: Diabetes mellitus 1; HSV: Herpes simplex virus; VZV: Varicella zoster virus; CMV: Cytomegalovirus, TB: Tuberculosis; HHV-6: Human herpesvirus 6; HZV: Herpes zoster virus; AIDS: Acquired immunodeficiency syndrome; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; RVO: Retinal vein occlusion; TBI: Traumatic brain injury; PCV: Polypoidal choroidal vasculopathy; HTN: Hypertension; FB: Foreign body; RAPD: Relative afferent pupillary defect; EOM: Extraocular movements; CNS: Central nervous system.

Table 2 Ocular symptoms, severity, and treatment strategies in autoimmune diseases

Ocular symptoms	Sever characteristics	Treatment options	Details	Ref.
Uveitis	Mild/moderate	Topical CS	Initial management for anterior uveitis; reduces redness and photophobia	[111-114]
	Severe	Systemic CS, systemic immunosuppressants	High-dose prednisone (> 60 mg daily); IV CS for acute cases (1000 mg/day for 3 days)	[113,115,125-127]
	Recurrent	Gradual CS taper	Reduce to 7.5 mg/day maintenance to prevent complications like cataracts	[113,116]
Keratitis	Mild	Environmental modifications	Avoid dry/windy conditions; avoid activities with reduced blinking	[117-119]
	Severe	Topical CS, lubricating drops, systemic immunosuppressants	Controls dryness, reduces inflammation	[117-119,125-128]
ON	Acute	High-dose IV CS	IV methylprednisolone 1 g/day for 3-7 days; followed by oral CS	[121,122]
Episcleritis	Mild	Low-dose CS or NSAIDs	Often self-resolving	[105]
Scleritis	Severe	Systemic CS, immunosuppressants	Controls inflammation	[105,123,125-128]
Chronic ocular inflammation	Chronic cases	Immunosuppressive agents	Methotrexate (first line for non-infectious cases), mycophenolate mofetil (chronic use), azathioprine, and cyclosporine	[129-133]
Refractory cases	Resistant to initial treatments	Alkylating agents (e.g., cyclophosphamide)	Reserved for severe, non-responsive cases due to toxicity	[134,135]

This table outlines the ocular symptoms associated with autoimmunity, categorizing them by severity and clinical characteristics. It highlights corresponding treatment options and provides additional details to guide clinical decision-making. The table includes both acute and chronic ocular conditions with specific therapeutic approaches for each. CS: Corticosteroids; IV: Intravenous; NSAIDs: Non-steroidal anti-inflammatory drugs; ON: Optical neuritis.

Table 3 Comparative biomarker table for ocular autoimmune and infectious disorders

Condition	Key biomarkers	Sensitivity (%)	Specificity (%)	Comments	Ref.
NMOSD	AQP4-IgG (live cell-based assay)	80%	100%	Highly specific; distinguishes NMOSD from MS-related optic neuritis	[148]
MS-related optic neuritis	No specific serological marker			Diagnosis is clinical and radiological; CSF oligoclonal bands may assist	[149]
MOG-AD	MOG-IgG (cell-based assay)	89.1%	93.3%	Important for recurrent optic neuritis with optic disc edema; often in children/young adults	[150]
Sarcoidosis-associated uveitis	ACE, lysozyme	ACE: 38.2%-84.0%; lysozyme: 60.0%-78.0%	ACE: 83.0%-97.8%; lysozyme: 76.0%-95.0%	Elevated levels support diagnosis; imaging often essential	[151]
TB-associated uveitis	QuantiFERON-TB gold	62%-95%	92%-100%	Latent TB testing critical in endemic areas or atypical uveitis	[152]
Behçet’s disease	HLA-B51			HLA-B51 is the strongest genetic association; supportive rather than diagnostic	[153]

NMOSD: Neuromyelitis optica spectrum disorders; AQP4: Aquaporin-4; MOG-AD: Myelin oligodendrocyte glycoprotein antibody disease antibody; ACE: Angiotensin converting enzyme; TB: Tuberculosis; CSF: Cerebrospinal fluid; MS: Multiple sclerosis; HLA: Human leukocyte antigen.