Differential Diagnosis of Ocular Signs

ANTERIOR CHAMBER/ANTERIOR CHAMBER ANGLE

Hyphema

Traumatic, iatrogenic (e.g., intraocular surgery or laser), iris neovascularization, herpes simplex or zoster iridocyclitis, blood dyscrasia or clotting disorder (e.g., hemophilia), anticoagulation, Fuchs heterochromic iridocyclitis, intraocular tumor (e.g., juvenile xanthogranuloma, retinoblastoma, angioma).

Hypopyon

Infectious corneal ulcer, endophthalmitis, severe iridocyclitis (e.g., HLA-B27 associated, Behcet disease), reaction to an intraocular lens (sterile hypopyon), retained lens particle, device contaminant after cataract surgery (toxic anterior segment syndrome), intraocular tumor necrosis (e.g., pseudohypopyon from retinoblastoma), retained intraocular foreign body, tight contact lens, chronic corneal edema with ruptured bullae, severe inflammatory reaction from a recurrent corneal erosion, drugs (e.g., rifampin).

Blood in Schlemm Canal on Gonioscopy

Compression of episcleral vessels by a gonioprism (iatrogenic), Sturge–Weber syndrome, arteriovenous fistula [e.g., carotid–cavernous sinus fistula (c-c fistula)], superior vena cava obstruction, hypotony.

CORNEA/CONJUNCTIVAL FINDINGS

Conjunctival Swelling (Chemosis)

Allergy, any ocular or periocular inflammation, postoperative, drugs, venous congestion (e.g., c-c fistula), angioneurotic edema, myxedema.

Conjunctival Dryness (Xerosis)

Vitamin A deficiency, postcicatricial conjunctivitis, Stevens–Johnson syndrome, ocular cicatricial pemphigoid, exposure (e.g., lagophthalmos, absent blink reflex, proptosis), radiation, chronic dacryoadenitis, Sjogren syndrome.

Corneal Crystals

See 4.14, Crystalline Keratopathy.

Corneal Edema

1. Congenital: Congenital glaucoma, congenital hereditary endothelial dystrophy (autosomal recessive form is present at birth, autosomal dominant form has later onset), posterior polymorphous dystrophy (PPMD), birth trauma (forceps injury).

2. Acquired: Postoperative edema, aphakic or pseudophakic bullous keratopathy, Fuchs endothelial dystrophy, contact lens overwear, traumatic, exposure, chemical injuries, acute increase in intraocular pressure (e.g. angle-closure glaucoma), corneal hydrops (decompensated keratoconus), herpes simplex or zoster keratitis, iritis, failed corneal graft, iridocorneal endothelial (ICE) syndrome, PPMD.

Dilated Episcleral Vessels (Without Ocular Irritation or Pain)

Underlying uveal neoplasm, arteriovenous fistula (e.g., c-c fistula), polycythemia vera, leukemia, ophthalmic vein or cavernous sinus thrombosis, extravascular blockage of ophthalmic/orbital venous outflow.

Enlarged Corneal Nerves

Most Important. Multiple endocrine neoplasia type IIb (medullary carcinoma of the thyroid gland, pheochromocytoma, mucosal neuromas; may have marfanoid habitus).

Others. Acanthamoeba keratitis, chronic keratitis, keratoconus, neurofibromatosis, Fuchs endothelial dystrophy, Refsum syndrome, trauma, congenital glaucoma, failed corneal graft, leprosy, ichthyosis, idiopathic, normal variant.

Follicles on the Conjunctiva

See 5.1, Acute Conjunctivitis, and 5.2, Chronic Conjunctivitis.

Membranous Conjunctivitis

(Removal of the membrane is difficult and causes bleeding). Streptococci, pneumococci, chemical burn, ligneous conjunctivitis, Corynebacterium diphtheriae, adenovirus, herpes simplex virus, ocular vaccinia. (Compare with “Pseudomembranous Conjunctivitis”.)

Pseudomembranous Conjunctivitis

(Removal of the pseudomembrane is easy without bleeding). See earlier for causes of membranous conjunctivitis, as well as ocular cicatricial pemphigoid, Stevens–Johnson syndrome, superior limbic keratoconjunctivitis, gonococci, staphylococci, chlamydia in newborns, and others.

Opacification of the Cornea in Infancy

Congenital glaucoma, birth trauma (forceps injury), congenital hereditary endothelial or stromal dystrophy (bilateral), PPMD, developmental abnormality of the anterior segment (e.g., Peters anomaly), metabolic abnormalities (bilateral; e.g., mucopolysaccharidoses, mucolipidoses), interstitial keratitis, herpes simplex virus, corneal ulcer, corneal dermoid, sclerocornea.

Pannus (Superficial Vascular Invasion of the Cornea)

Ocular rosacea, tight contact lens or contact lens overwear, phlyctenule, chlamydia (trachoma and inclusion conjunctivitis), superior limbic keratoconjunctivitis (micropannus only), staphylococcal hypersensitivity, vernal keratoconjunctivitis, herpes simplex or zoster virus, chemical burn, ocular cicatricial pemphigoid, aniridia, molluscum contagiosum, leprosy.

Papillae on the Conjunctiva

See 5.1, Acute Conjunctivitis, and 5.2, Chronic Conjunctivitis.

Pigmentation/Discoloration of the Conjunctiva

Racial melanosis (perilimbal), nevus, primary acquired melanosis, melanoma, ocular and oculodermal melanocytosis (congenital, blue-gray, not conjunctival but episcleral), Addison disease, pregnancy, radiation, jaundice, resolving subconjunctival hemorrhage, mascara, conjunctival or subconjunctival foreign body, pharmacologic (e.g., chlorpromazine, topical epinephrine).

Symblepharon (Fusion of the Palpebral Conjunctiva with the Bulbar Conjunctiva)

Ocular cicatricial pemphigoid, Stevens–Johnson syndrome, chemical burn, trauma, drugs, long-standing conjunctival or episcleral inflammation, epidemic keratoconjunctivitis, atopic conjunctivitis, radiation, congenital, iatrogenic (postsurgical).

Whorl-Like Opacity in the Corneal Epithelium (Verticillata)

Amiodarone, chloroquine, Fabry disease and carrier state, phenothiazines, indomethacin.

EYELID ABNORMALITIES

Eyelid Edema

See “Eyelid Swelling” in Chapter 1, Differential Diagnosis of Ocular Symptoms.

Eyelid Lesion

See 6.11, Malignant Tumors of the Eyelid.

Ptosis and Pseudoptosis

See 6.1, Ptosis.

FUNDUS FINDINGS

Bone Spicules (Widespread Pigment Clumping)

See 11.28, Retinitis Pigmentosa and Inherited Chorioretinal Dystrophies.

Bull’s-Eye Macular Lesion

Age-related macular degeneration (ARMD), Stargardt disease or fundus flavimaculatus, albinism, cone dystrophy, chloroquine or hydroxychloroquine retinopathy, Spielmeyer–Vogt syndrome, central areolar choroidal dystrophy. See 11.32, Chloroquine/Hydroxychloroquine Toxicity.

Choroidal Folds

Orbital or choroidal tumor, idiopathic orbital inflammatory syndrome, thyroid eye disease, posterior scleritis, hypotony, retinal detachment, marked hyperopia, scleral laceration, papilledema, postoperative.

Choroidal Neovascularization (Gray-Green Membrane or Blood Seen Deep to the Retina)

More Common. ARMD, ocular histoplasmosis syndrome, high myopia, idiopathic polypoidal choroidal vasculopathy, angioid streaks, choroidal rupture (trauma).

Less Common. Drusen of the optic nerve head, tumors, retinal scarring after laser photocoagulation, idiopathic.

Cotton–Wool Spots

See 11.5, Cotton–Wool Spot.

Embolus

See 10.22, Transient Visual Loss/Amaurosis Fugax; 11.6, Central Retinal Artery Occlusion; 11.7, Branch Retinal Artery Occlusion; 11.33, Crystalline Retinopathy.

Platelet–fibrin (dull gray and elongated): Carotid disease, less common cardiac.

Cholesterol (sparkling yellow, usually at an arterial bifurcation): Carotid disease.

Calcium (dull white, typically around or on the disc): Cardiac disease.

Cardiac myxoma (common in young patients, particularly in the left eye; often occludes the ophthalmic or central retinal artery behind the globe and is not seen).

Talc and cornstarch (small yellow-white glistening particles in macular arterioles; may produce peripheral retinal neovascularization): Intravenous (i.v.) drug abuse.

Lipid or air (cotton–wool spots, not emboli, are often seen): Results from chest trauma (Purtscher retinopathy) and fracture of long bones.

Others (tumors, parasites, other foreign bodies).

Macular Exudates

More Common. Diabetes, choroidal (subretinal) neovascular membrane, hypertension.

Less Common. Macroaneurysm, Coats disease (children), peripheral retinal capillary hemangioma, retinal vein occlusion, papilledema, radiation retinopathy.

Normal Fundus in the Presence of Decreased Vision

Retrobulbar optic neuritis, cone degeneration, Stargardt disease or fundus flavimaculatus, other optic neuropathy (e.g., Leber hereditary optic neuropathy, tumor, alcohol or tobacco), rod monochromatism, amblyopia, nonphysiologic visual loss.

Optociliary Shunt Vessels on the Disc

Orbital or intracranial tumor (especially meningioma), previous central retinal vein occlusion, chronic papilledema (e.g., pseudotumor cerebri), chronic open-angle glaucoma, optic nerve glioma.

Retinal Neovascularization

1. Posterior pole: Diabetes, after central retinal vein occlusion.

2. Peripheral: Sickle cell retinopathy, after branch retinal vein occlusion, diabetes, sarcoidosis, syphilis, ocular ischemic syndrome (carotid occlusive disease), pars planitis, Coats disease, retinopathy of prematurity, embolization from i.v. drug abuse (talc retinopathy), chronic uveitis, others (e.g., leukemia, anemia, Eales disease, familial exudative vitreoretinopathy).

Roth Spots (Retinal Hemorrhages with White Centers)

More Common. Diabetes, leukemia, septic chorioretinitis (e.g., secondary to bacterial endocarditis).

Less Common. Pernicious anemia (and rarely other forms of anemia), sickle cell disease, scurvy, systemic lupus erythematosus, other connective tissue diseases.

Sheathing of Retinal Veins (Periphlebitis)

More Common. Syphilis, sarcoidosis, pars planitis, sickle cell disease.

Less Common. Tuberculosis, multiple sclerosis, Eales disease, viral retinitis (e.g., human immunodeficiency virus, herpes), Behçet disease, fungal retinitis, bacteremia.

Tumor

See 11.36, Choroidal Nevus and Malignant Melanoma of the Choroid.

INTRAOCULAR PRESSURE

Acute Increase in Intraocular Pressure

Acute angle-closure glaucoma, glaucomatocyclitic crisis (Posner–Schlossman syndrome), inflammatory open-angle glaucoma, malignant glaucoma, postoperative (see “Postoperative Problems,” this chapter), suprachoroidal hemorrhage, hyphema, c-c fistula, retrobulbar hemorrhage, or other orbital disease.

Chronic Increase in Intraocular Pressure

See 9.1, Primary Open-Angle Glaucoma.

Decreased Intraocular Pressure (Hypotony)

Ruptured globe, phthisis bulbi, retinal/choroidal detachment, iridocyclitis, severe dehydration, cyclodialysis cleft, ocular ischemia, drugs (e.g., glaucoma medications), postoperative (see “Postoperative Problems,” this chapter), traumatic ciliary body shutdown.

IRIS

Iris Heterochromia (Irides of Different Colors)

1. Involved iris is lighter than normal: Congenital Horner syndrome, most cases of Fuchs heterochromic iridocyclitis, chronic uveitis, juvenile xanthogranuloma, metastatic carcinoma, Waardenburg syndrome.

2. Involved iris is darker than normal: Ocular melanocytosis or oculodermal melanocytosis, hemosiderosis, siderosis, retained intraocular foreign body, ocular malignant melanoma, diffuse iris nevus, retinoblastoma, leukemia, lymphoma, ICE syndrome, some cases of Fuchs heterochromic iridocyclitis.

Iris Lesion

1. Melanotic (brown): Nevus, melanoma, adenoma, or adenocarcinoma of the iris pigment epithelium.

NOTE: Cysts, foreign bodies, neurofibromas, and other lesions may appear pigmented in heavily pigmented irides.

2. Amelanotic (white, yellow, or orange): Amelanotic melanoma, inflammatory nodule or granuloma (e.g., sarcoidosis, tuberculosis, leprosy, other granulomatous disease), neurofibroma, patchy hyperemia of syphilis, juvenile xanthogranuloma, foreign body, cyst, leiomyoma, seeding from a posterior segment tumor.

Neovascularization of the Iris

Diabetic retinopathy, ocular ischemic syndrome, after central or branch retinal vein or artery occlusion, chronic uveitis, chronic retinal detachment, intraocular tumor (e.g., retinoblastoma, melanoma), other retinal vascular disease.

Lens (See Also 13.1, Acquired Cataract)

Dislocated Lens (Ectopia Lentis)

See 13.10, Subluxed or Dislocated Crystalline Lens.

Iridescent Lens Particles

Drugs, hypocalcemia, myotonic dystrophy, hypothyroidism, familial, idiopathic.

Lenticonus

1. Anterior (marked convexity of the anterior lens): Alport syndrome (hereditary nephritis).

2. Posterior (marked concavity of the posterior lens surface): Usually idiopathic, may be associated with persistent fetal vasculature.

NEUROOPHTHALMIC ABNORMALITIES

Afferent Pupillary Defect

1. Severe (2+ to 3+): Optic nerve disease (e.g., ischemic optic neuropathy, optic neuritis, tumor, glaucoma); central retinal artery or vein occlusion; less commonly, a lesion of the optic chiasm or tract.

2. Mild (1+): Any of the preceding, amblyopia, dense vitreous hemorrhage, advanced macular degeneration, branch retinal vein or artery occlusion, retinal detachment, or other retinal disease.

Anisocoria (Pupils of Different Sizes)

See 10.1, Anisocoria.

Limitation of Ocular Motility

1. With exophthalmos and resistance to retropulsion: See 7.1, Orbital Disease.

2. Without exophthalmos and resistance to retropulsion: Isolated third, fourth, or sixth cranial nerve palsy; multiple ocular motor nerve palsies [see 10.10, Cavernous Sinus and Associated Syndromes (Multiple Ocular Motor Nerve Palsies)], myasthenia gravis, chronic progressive external ophthalmoplegia and associated syndromes, orbital blow-out fracture with muscle entrapment, ophthalmoplegic migraine, Duane syndrome, other central nervous system (CNS) disorders.

Optic Disc Atrophy

More Common. Glaucoma; after central retinal vein or artery occlusion; previous ischemic optic neuropathy; chronic optic neuritis; chronic papilledema; compression of the optic nerve, chiasm, or tract by a tumor or aneurysm; previous traumatic optic neuropathy.

Less Common. Syphilis, retinal degeneration (e.g., retinitis pigmentosa), toxic or metabolic optic neuropathy, Leber hereditary optic atrophy, Leber congenital amaurosis, lysosomal storage disease (e.g., Tay–Sachs), radiation neuropathy, other forms of congenital or hereditary optic atrophy (nystagmus almost always present in congenital forms).

Optic Disc Swelling (Edema)

See 10.15, Papilledema.

Optociliary Shunt Vessels

See “Fundus Findings” in this chapter.

Pardoxical Pupillary Reaction (Pupil Dilates in Light and Constricts in Darkness)

Congenital stationary night blindness, congenital achromatopsia, optic nerve hypoplasia, Leber congenital amaurosis, Best disease, optic neuritis, dominant optic atrophy, albinism, retinitis pigmentosa. Rarely amblyopia.

ORBIT

Extraocular Muscle Thickening on Imaging

More Common. Thyroid orbitopathy (often spares tendon), idiopathic orbital inflammatory syndrome.

Less Common. Tumor (e.g., lymphoma, metastasis, or spread of lacrimal gland tumor to muscle), c-c fistula, superior ophthalmic vein thrombosis, cavernous hemangioma (usually appears in the muscle cone without muscle thickening), rhabdomyosarcoma (children).

Lacrimal Gland Lesions

See 7.6, Lacrimal Gland Mass/Chronic Dacryoadenitis.

Optic Nerve Lesion (Isolated)

More Common. Optic nerve glioma (especially children), optic nerve meningioma (especially adults).

Less Common. Metastasis, leukemia, idiopathic orbital inflammatory syndrome, sarcoidosis, increased intracranial pressure with secondary optic nerve swelling.

Orbital Lesions/Proptosis

See 7.1, Orbital Disease.

PEDIATRICS

Leukocoria (White Pupillary Reflex)

See 8.1, Leukocoria.

Nystagmus In Infancy (See Also 10.21, Nystagmus)

Congenital nystagmus, albinism, Leber congenital amaurosis, CNS (thalamic) injury, spasmus nutans, optic nerve or chiasmal glioma, optic nerve hypoplasia, congenital cataracts, aniridia, congenital corneal opacities.

POSTOPERATIVE COMPLICATIONS

Shallow Anterior Chamber

1. Accompanied by increased intraocular pressure: Pupillary block glaucoma, suprachoroidal hemorrhage, malignant glaucoma.

2. Accompanied by decreased intraocular pressure: Wound leak, choroidal detachment, over filtration after glaucoma filtering procedure.

Hypotony

Wound leak, choroidal detachment, cyclodialysis cleft, retinal detachment, ciliary body shutdown, pharmacologic aqueous suppression.

REFRACTIVE PROBLEMS

Progressive Hyperopia

Orbital tumor pressing on the posterior surface of the eye, serous elevation of the retina (e.g., central serous chorioretinopathy), posterior scleritis, presbyopia, hypoglycemia, cataracts, after radial keratotomy, or other refractive surgery.

Progressive Myopia

High (pathologic) myopia, diabetes, cataract, staphyloma and elongation of the globe, corneal ectasia (keratoconus or after corneal refractive surgery), medications (e.g., miotic drops, sulfa drugs, tetracycline), childhood (physiologic).

VISUAL FIELD ABNORMALITIES

Altitudinal Field Defect

More Common. Ischemic optic neuropathy, hemi or branch retinal artery or vein occlusion, optic neuritis.

Less Common. Glaucoma, optic nerve or chiasmal lesion, optic nerve coloboma.

Arcuate Scotoma

More Common. Glaucoma.

Less Common. Ischemic optic neuropathy (especially nonarteritic), optic disc drusen, high myopia, optic neuritis.

Binasal Field Defect

More Common. Glaucoma, bitemporal retinal disease (e.g., retinitis pigmentosa).

Rare. Bilateral occipital disease, tumor or aneurysm compressing both optic nerves or chiasm, chiasmatic arachnoiditis, nonphysiologic.

Bitemporal Hemianopsia

More Common. Chiasmal lesion (e.g., pituitary adenoma, meningioma, craniopharyngioma, aneurysm, glioma).

Less Common. Tilted optic discs.

Rare. Nasal retinitis pigmentosa.

Blind Spot Enlargement

Papilledema, glaucoma, optic nerve drusen, optic nerve coloboma, myelinated (medullated) nerve fibers off the disc, drugs, myopic disc with a crescent, multiple evanescent white dot syndrome (MEWDS), acute idiopathic blind spot enlargement syndrome [(AIBSE) may be on spectrum with MEWDS].

Central Scotoma

Macular disease; optic neuritis; ischemic optic neuropathy (more typically produces an altitudinal field defect); optic atrophy (e.g., from tumor compressing the nerve, toxic or metabolic disease); rarely, an occipital cortex lesion.

Constriction of the Peripheral Fields Leaving a Small Residual Central Field (Tunnel Vision)

Glaucoma; retinitis pigmentosa, or other peripheral retinal disorders (e.g., gyrate atrophy); chronic papilledema; status-
post panretinal photocoagulation or cryotherapy, central retinal artery occlusion with cilioretinal artery sparing; bilateral occipital lobe infarction with macular sparing; nonphysiologic visual loss; carcinoma, melanoma, and autoimmune-associated retinopathy; rarely, medications (e.g., phenothiazines); vitamin A deficiency.

Homonymous Hemianopsia

Optic tract or lateral geniculate body lesion; temporal, parietal, or occipital lobe lesion of the brain (stroke and tumor more common; aneurysm and trauma less common). Migraine may cause a transient homonymous hemianopsia.

VITREOUS

Vitreous Opacities

Asteroid hyalosis; synchysis scintillans; vitreous hemorrhage; inflammatory cells from vitritis or posterior uveitis; snowball opacities of pars planitis or sarcoidosis; normal vitreous strands from age-related vitreous degeneration; tumor cells; foreign body; hyaloid remnants; rarely, amyloidosis or Whipple disease.

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