(From Zangwill L, de Souza K, Weinrob RN: Confocal scanning laser ophthalmoscopy to detect glaucomatous optic neuropathy. In Shuman JS [ed]: Imaging in Glaucoma. Thorofare, NJ, Slack, 1997.)

Optical coherence tomography (OCT)

measures optical backscattering of light to produce high-resolution, cross-sectional image of the NFL (Figure 9-8)

Figure 9-8 Optical coherence tomography.

(From Pedut-Kloizman TP, Schuman JS: Disc analysis. In Yanoff M, Duker JS [eds]: Ophthalmology, London, Mosby, 1999.)

Scanning laser polarimetry (SLP; Nerve Fiber Analyzer, GDx)

uses a confocal scanning laser ophthalmoscope with an integrated polarimeter to detect changes in light polarization from axons to measure the NFL thickness; quantitative analysis of NFL thickness to detect early glaucomatous damage (Figure 9-9)

Figure 9-9 Printout from the GDx software of the Nerve Fiber Analyzer; normal eye.

(From Chopin NT: Retinal nerve fiber layer analysis. In Yanoff M, Duker JS [eds]: Ophthalmology, London, Mosby, 1999.)

Optic nerve blood flow measurement

color Doppler imaging and laser Doppler flowmetry (Figure 9-10)

Figure 9-10 Color Doppler imaging of the ophthalmic artery.

(From O’Brien C, Harris A: Optic nerve blood flow measurement. In Yanoff M, Duker JS [eds]: Ophthalmology, London, Mosby, 1999.)

Pathology

Glaucoma

Dropout of ganglion cells, replacement of NFL with dense gliotic tissue and some glial cell nuclei; partial preservation of inner nuclear layer with loss of Müller’s and amacrine cells (normal 8–9 cells high; in glaucoma, 4–5 cells high); earliest histologic changes occur at level of lamina cribrosa; advanced cases may show backward bowing of lamina or ‘beanpot’ appearance (Figures 9-11, 9-12)

Figure 9-11 POAG demonstrating cupping of the optic nerve head.

(From Yanoff M, Fine BS: Ocular Pathology, 5th edn. St Louis, Mosby, 2002.)

Figure 9-12 POAG demonstrating atrophy of the inner retinal layers. A, low power, B, higher magnification.

(From Yanoff M, Fine BS: Ocular Pathology, 5th edn, St Louis, Mosby, 2002.)

Schnabel’s Cavernous Optic Atrophy

Histologic finding in eyes with increased IOP or atherosclerosis and normal IOP; hyaluronic acid infiltration of nerve from vitreous due to imbalance between perfusion pressure in the posterior ciliary arteries and IOP; also occurs in eyes with ischemic optic neuropathy

Pathology

atrophy of neural elements with cystic spaces containing hyaluronic acid (mucopolysaccharides derived from vitreous), which stains with colloidal iron (Figure 9-13)

Figure 9-13 Schnabel’s cavernous optic atrophy demonstrating cystic spaces in optic nerve parenchyma. A, H&E stain, B, colloidal iron stain.

(From Yanoff M, Fine BS: Ocular Pathology, 5th edn. St Louis, Mosby, 2002.)

Gliosis of the Optic Nerve

With optic atrophy, glial cells replace nerve cells and assume a random distribution throughout the optic nerve

Disorders

Childhood Glaucoma

(See Ch. 5, Pediatrics/Strabismus)

Primary Open-Angle Glaucoma (POAG)

Progressive, bilateral, optic neuropathy with open angles, typical pattern of nerve fiber bundle visual field loss, and increased intraocular pressure (IOP >21 mmHg) not caused by another systemic or local disease

Epidemiology

second leading cause of blindness in US; most common form of glaucoma (60–70%); 7% of population has ocular hypertension; 3% of population in Baltimore Eye Study had glaucomatous VF defects. If damage in one eye, untreated fellow eye has 29% risk over 5 years. Steroid responders have 31% risk of developing glaucoma within 5 years

Genetics

juvenile-onset POAG has been mapped to chromosome 1q21-q31 (GLC1A, MYOC/TIGR). Adult POAG has been mapped to chromosomes 2qcen-q13 (GLC1B), 2p15-p16 (GLC1H), 3q21-q24 (GLC1C), 8q23 (GLC1D), 10p14 (GLC1E, OPTN [optineurin]). A mutation in the OPTN gene accounts for ∼17% of POAG

Risk factors

increased IOP, increased cup-to-disc ratio, thinner central corneal thickness (less than ∼550 µm), positive family history (6× increase in first-degree relatives), age (increased in patients >60 years old; 15% of those >80 years old have glaucoma), race (6× increase in African Americans vs Caucasians); other possible risk factors include DM, myopia, hypertension, migraines

Pathogenesis

unknown

Theories of optic nerve damage:

Mechanical: resistance to outflow, trabecular meshwork dysfunction

Vascular: poor optic nerve perfusion; ischemia occurs with systemic hypotension; possible contribution of vasospasm; increased IOP reduces blood flow to optic nerve

Ganglion cell necrosis or apoptosis: excitotoxicity (glutamate), neurotrophin starvation, autoimmunity, abnormal glial-neuronal interactions (tumor necrosis factor [TNF]), defects in endogenous protective mechanisms (heat shock proteins)

Findings

increased IOP, large cup-to-disc ratio (especially vertical elongation of optic cup; notching of rim; asymmetry of C/D ratio), nerve fiber layer loss (evaluate with red-free light), disc splinter hemorrhage (often followed by notching in region of hemorrhage), characteristic visual field defects. Peripapillary atrophy is not a sign of glaucoma damage

With optic nerve damage, loss of yellow-blue color axis occurs first

Combined sensitivity of tonometry and disc exam = 67%

Visual fields

sensitivity (% of diseased properly identified) = 85%; specificity (% of normals properly identified) = 85%. Risk of initial field loss is 1–2%/year for ocular hypertensive patients, risk of field loss increases with increasing IOP

Secondary Open-Angle Glaucoma

Mechanism/Etiology

Clogging of TM: RBCs (hyphema, sickle cell, ghost cells), macrophages (hemolytic, phacolytic, melanocytic, melanomalytic), neoplastic cells (malignant tumors, neurofibromatosis, juvenile xanthogranuloma), pigment (pigmentary glaucoma, pseudoexfoliation, chronic uveitis, malignant melanoma), lens protein (lens-particle glaucoma), photoreceptor segments (Schwartz’s syndrome), zonular fragments (α-chymotrypsin induced), viscoelastic

Toxic/medication: steroid-induced, siderosis, chalcosis

Inflammation: uveitis, IK

Increased episcleral venous pressure

Trauma: angle recession, chemical injury, hemorrhage, postoperative

Hyphema

27% risk of glaucoma if hyphema >50% of AC volume; 52% risk with total hyphema

Surgical intervention for uncontrolled IOP, corneal blood staining, prolonged presence of clot (>15 days), rebleed, 8-ball hyphema (see Ch. 10, Anterior Segment)

Sickle cell

Sickled cells are rigid; therefore, even small hyphemas can obstruct TM and raise IOP; acetazolamide (Diamox) contraindicated (increases ascorbic acid in AC causing greater sickling, also causes hemoconcentration and systemic acidosis, both of which favor sickling)

Ghost cells

Weeks to months after vitreous hemorrhage, degenerated RBCs pass through hyaloid face. These khaki-colored, spherical cells are less pliable than RBCs and do not pass through trabecular meshwork; layer of cells forms a pseudohypopyon

Tumor cells

Deposition of tumor cells, inflammatory cells, and cellular debris; also macrophages laden with melanin from melanomas, direct infiltration of trabecular meshwork, or neovascularization with subsequent intraocular hemorrhage or neovascular glaucoma (NVG). 45% of anterior uveal melanomas and 15% of choroidal melanomas are associated with glaucoma. Retinoblastoma causes glaucoma in 25–50% from NVG, pupillary block, or tumor material; also lymphoma

Pigmentary glaucoma (PG) (AD)

Mapped to chromosome 7q35-q36 (GLC1F)

Typically young myopic males; up to 50% of patients with pigment dispersion syndrome (PDS) develop glaucoma

Mechanism

reverse pupillary block bows iris against zonules, and iris movement results in pigment liberation; pigment obstructs TM

Findings

halos and blurry vision with IOP spikes (pigment may be released with exercise); Krukenberg spindle (melanin phagocytized by corneal endothelium); heavy TM pigmentation; iridodonesis; iris transillumination defects (radial midperipheral spoke-like appearance); associated with lattice degeneration (20%) and retinal detachment (5%) (Figure 9-14)

Figure 9-14 Gonioscopic view of pigmentary glaucoma.

(From Ball SF: Pigmentary glaucoma. In Yanoff M, Duker JS [eds]: Ophthalmology, London, Mosby, 1999.)

Treatment

miotics minimize iris-zonule touch; very good response to laser trabeculoplasty; laser peripheral iridotomy may help reduce posterior bowing of iris

Pseudoexfoliation glaucoma (PXG)

Mapped to chromosome 15q24 (LOXL1).

High incidence (up to 50%) of secondary open-angle glaucoma in patients with pseudoexfoliation syndrome (PXS); more common among Scandinavians. Amyloid-like substance deposits in eye and clogs TM, also found in other organs (Figure 9-15)

Figure 9-15 Pseudoexfoliative syndrome demonstrating exfoliative material on lens capsule.

(From Samuelson TW, Shah G: Pseudoexfoliative glaucoma. In: Yanoff M, Duker JS [eds]: Ophthalmology, London, Mosby, 1999.)

Findings

iridopathy (blood-aqueous barrier defect, pseudouveitis, iris rigidity, posterior synechiae, poor pupillary dilation), keratopathy (reduced endothelial cell count, endothelial decompensation, corneal endothelial proliferation over trabecular meshwork), Sampaolesi’s line (scalloped band of pigmentation anterior to Schwalbe’s line), weak zonules (phacodonesis, risk of lens dislocation during cataract surgery, and angle closure from anterior movement of lens), lens capsule (white fibrillar material)

High IOP associated with rhegmatogenous RD. Photoreceptor outer segments migrate transvitreally into aqueous and block trabecular meshwork; outflow obstruction is also due to pigment released from RPE and glycosaminoglycans released from photoreceptors. Usually resolves after repair of RD

Alpha-chymotrypsin induced

Zonular fragments accumulate in trabecular meshwork after intracapsular cataract extraction (ICCE) with enzymatic zonulysis. Alpha-chymotrypsin itself does not cause damage

Corticosteroid-induced

Risk factors include open-angle glaucoma, family history of glaucoma, increasing age, diabetes, and high myopia. Topical steroids have greater pressure-raising effects than do systemic steroids:

In response to topical dexamethasone 0.1% qid for 6 weeks, 65% had IOP rise of <5 mmHg, 30% had a rise of 5–14 mmHg, and 5% had a rise of at least 15 mmHg

Fluoromethalone, rimexolone (Vexol), and loteprednol (Lotemax, Alrex) are less likely to increase IOP

Siderosis (iron) or chalcosis (copper)

TM toxicity and scarring from intraocular foreign body

Uveitic

Normally, a decrease in aqueous production by the ciliary body occurs due to inflammation (trabeculitis); however, aqueous outflow is acutely impaired by the disruption of the blood-aqueous barrier and inflammatory cells. Chronic inflammation may cause TM scarring

carotid-cavernous sinus fistula, cavernous sinus thrombosis, Sturge-Weber syndrome, neurofibromatosis, orbital mass (tumor, varices), thyroid-related ophthalmopathy (false elevation of IOP can be caused by IR fibrosis with increased resistance in upgaze), superior vena cava obstruction, mediastinal tumors and syndromes, idiopathic. May see blood in Schlemm’s canal

Primary Angle-Closure Glaucoma

Glaucoma caused by peripheral iris obstructing the trabecular meshwork, most commonly due to pupillary block; classified as acute, intermittent, or chronic. Plateau iris syndrome is a form of primary angle-closure without pupillary block

Mechanism of pupillary block

in susceptible patients, iridolenticular touch causes resistance of aqueous flow from posterior to anterior chamber, causing increased posterior pressure. When the pupil is mid-dilated (i.e. stress, low ambient light levels, sympathomimetic or anticholinergic medications), the elevated posterior chamber pressure causes peripheral iris tissue to bow forward and occlude the TM

Epidemiology

acute form is most common in Eskimos and Asians, followed by Caucasians, then African Americans; highest risk is between age 55 and 65 years old; more common in women only among Caucasians. Chronic form is more common in African Americans than Asians, who have a higher risk than Caucasians. 5% of population older than 60 years of age have angles that can be occluded; 0.5% of these individuals develop angle closure. Usually bilateral (75% risk in untreated fellow eye within 5 years)

high IOP, corneal epithelial edema, conjunctival injection, mid-dilated pupil, shallow anterior chamber, mild AC cell and flare, closed angle (perform indentation gonioscopy to differentiate between appositional and synechial angle closure; glycerin can be used to clear corneal edema; evaluate angle in other eye), ON swelling and hyperemia; with rapid rise in IOP, may see arterial pulsations (retinal ischemia can occur)

α-adrenergic antagonist used to distinguish angle closure from glaucoma with narrow angles; thymoxamine blocks iris dilator muscle producing miosis; however, it does not affect trabecular meshwork and normally does not decrease IOP; therefore, decrease in IOP suggests miosis has removed iris from the outflow channel reversing angle closure

Treatment of acute angle-closure glaucoma

peripheral iridotomy or iridectomy (PI, definitive treatment); compression gonioscopy (may force aqueous through block and open angle); pilocarpine (may not be effective at IOP >40 mmHg due to sphincter ischemia; may also cause lens–iris diaphragm to move forward, worsening pupillary block); reduce IOP with β-blocker, α₂-agonist, topical or oral CAI, or hyperosmotic agent (isosorbide, glycerin [contraindicated in diabetics], or IV mannitol [risk of cardiovascular adverse effects]); topical steroids for inflammation; laser PI in fellow eye (75% chance of attack in untreated fellow eye; pilocarpine lowers risk to 40% but may lead to chronic angle closure)

If attack of angle closure is broken medically, consider waiting a few days before performing laser PI because corneal edema, iridocorneal touch, and iris congestion make the procedure more difficult

Persistently increased IOP following laser PI may be due to PAS, incomplete iridotomy, underlying open-angle glaucoma, or secondary angle closure

Intermittent angle closure

2 : 1 ratio of nonacute-to-acute presentations; may be asymptomatic or have similar presentation as acute angle closure but less severe, and occurs over days to weeks; often complain of headaches, episodes resolve spontaneously, especially by entering a well-lit area (induces miosis); IOP may be normal, glaukomflecken and PAS are evidence of previous attack. Treat with laser PI

Chronic angle closure

Gradual closure of angle by apposition or development of PAS leads to slow rise in IOP; variable IOP, but less than with acute angle closure. Often asymptomatic; cornea usually clear due to gradual rise in IOP, but can have extensive visual field loss

may present with acute or chronic angle closure; anteriorly positioned ciliary processes force the peripheral iris more anteriorly than normal; deep chamber centrally; flat iris contour with sharp dropoff peripherally; with dilation, peripheral iris folds into the angle and occludes TM; with compression gonioscopy, angle is more difficult to open and does not open as widely as in primary angle closure

With pupillary block: phacomorphic (lens enlargement in elderly; urgent surgery needed to remove lens); dislocated lens; seclusio pupillae; nanophthalmos; aphakic and pseudophakic pupillary block; silicone oil (prevent by performing an inferior PI because oil is lighter than water)

Without pupillary block:

POSTERIOR ‘PUSHING’ MECHANISM (mechanical/anterior displacement of lens–iris diaphragm)

ANTERIOR ROTATION OF CILIARY BODY: inflammation (scleritis, uveitis, after scleral buckle or panretinal photocoagulation [PRP]), congestion (postscleral buckling, nanophthalmos), choroidal effusion (hypotony; uveal effusion), suprachoroidal hemorrhage

AQUEOUS MISDIRECTION (MALIGNANT GLAUCOMA)

PRESSURE FROM POSTERIOR SEGMENT: tumor, expanding gas, exudative retinal detachment (RD)

CONTRACTION OF RETROLENTAL TISSUE: persistent hyperplastic primary vitreous (PHPV), retinopathy of prematurity (ROP)

ANTERIOR ‘PULLING’ MECHANISM (adherence of iris to trabecular meshwork/membranes over TM)

EPITHELIAL: epithelial downgrowth, fibrous ingrowth

ENDOTHELIAL: iridocorneal endothelial (ICE) syndrome, posterior polymorphous dystrophy (PPMD)

NEOVASCULAR: neovascular glaucoma (NVG)

PERIPHERAL ANTERIOR SYNECHIAE (PS)

ADHESION FROM TRAUMA

>10 D hyperopia; small eye (<20 mm) with small cornea (mean diameter = 10.5 mm), shallow AC, narrow angle, and high lens/eye volume. Pupillary block or uveal effusion produces angle-closure glaucoma. Thick sclera (about 2× thicker than normal) may impede vortex venous drainage, as well as decrease uveoscleral outflow, and can also result in spontaneous uveal effusion with anterior rotation of CB leading to angle closure

Treatment

weak miotics, cycloplegics (if no angle crowding), laser PI, laser iridoplasty, trabeculectomy after prophylactic sclerotomy. Because there is a high complication rate with surgery (uveal effusion), first use medical therapy, then laser

Increased risk of complications with cataract surgery (RD, choroidal effusion, angle-closure glaucoma, flat AC, CME, corneal decompensation, malignant glaucoma, IOL miscalculations). If shallow AC and thickened choroid preoperatively, perform prophylactic anterior sclerotomies with surgery

uveitis, angle closure, nanophthalmos, hyperopia; occurs postoperatively (usually 5 days) following a variety of laser or incisional surgeries; usually in patients with PAS or chronic angle closure following intraocular surgery if the hyaloid face has not been broken (follows 2% of surgical cases for angle closure); can also occur in unoperated eye when mydriatics are stopped or miotics are added

Medical: cycloplegic (relaxes ciliary muscle and pulls lens-iris diaphragm posteriorly; continued indefinitely to prevent recurrence), aqueous suppressants, peripheral iridotomy in both eyes (eliminate any component of pupillary block); miotics are contraindicated

50% resolve within 5 days with medical therapy alone

Surgical: argon laser photocoagulation of ciliary processes (requires shrinkage of at least 2–4 ciliary processes), Nd : YAG laser rupture of hyaloid face (for pseudophakic and aphakic patients; 4–6 mJ; best to perform peripherally [through PI]), vitrectomy (for phakic patients; debulk vitreous and overdeepen AC with air)

Intraocular tumors

Can push angle closed from posteriorly

Malignant melanoma of the anterior uveal tract can cause glaucoma by direct extension of tumor into trabecular meshwork, inducing neovascularization of the angle, obstructing TM with melanin-laden macrophages (melanomalytic), or seeding of tumor cells in outflow channels; other mechanisms include pigment dispersion, inflammation, and hemorrhage

proliferative retinopathy (diabetes [33% of all forms of NVG], ischemic CRVO [33%], carotid occlusive disease [13%], ciliary artery occlusion, sickle cell, Norrie’s disease, ROP); intraocular inflammation (uveitis, postoperative); neoplasms (retinoblastoma [50% develop NVG], malignant melanoma, large cell lymphoma [reticulum cell sarcoma], metastatic); chronic retinal detachment

Treatment

aqueous suppressants and hyperosmotics; increase uveoscleral outflow (atropine; avoid miotics); panretinal photocoagulation; peripheral retinal cryotherapy (if poor visualization of retina; 50% develop phthisis with cyclocryotherapy); glaucoma drainage implant (70% success rate)

Normal Tension Glaucoma (NTG)

Glaucoma with open angles and IOP <22 mmHg

Proposed mechanisms

Nocturnal systemic hypotension: diurnal curve of BP similar to IOP. 66% of patients will have a BP drop of greater than 10% during early morning hours (’dippers’); patients with HTN have an even greater swing in BP (26% average drop); patients with HTN treated with β-blockers can have diastolic BP <50 mmHg, which may compromise blood supply to optic nerve

Autoimmune: increased incidence of proteinemia and autoantibodies in patients with NTG

Vasospasm

Previous hemodynamic crisis: excessive blood loss or shock

Findings

VF defects in NTG have steeper slopes, greater depths, and closer proximity to fixation than in POAG; splinter hemorrhages are more common

DDx

POAG with large diurnal variation, ‘burned-out’ secondary open-angle glaucoma, chronic angle closure. Must rule out intracranial processes and other causes of optic neuropathy

Cupping can occur with neurologic disease: AION (arteritic 50%; nonarteritic 10%), chiasmal compressive lesions (5%), optic neuritis (<5%), methanol toxicity. These entities are more likely to have early loss of central vision and color vision; pallor may be worse than cupping

Diagnosis

diurnal curve, neurologic workup (CBC, ESR, ANA, VDRL and FTA-ABS, carotid evaluation, brain neuroimaging)

Prognosis

more difficult to treat than POAG

Treatment

Generally, medications are tried first, followed by laser treatment, and then surgery; however, the choice and timing of various treatment modalities are dependent on the type of glaucoma, severity of optic nerve damage, level of control, and many other factors. Therapy must also be directed to any preexisting or underlying process

(From Schwartz AL: Argon Laser Trabeculoplasty in Glaucoma: What’s Happening (Survey Results of American Glaucoma Society Members), J Glaucoma 2:329-336, 1993.)

Iopidine immediately postoperatively to avoid pressure spike, and treat with steroids for 1 week. Assess efficacy of treatment at 6 weeks postoperatively

Anterior burns have poor effect; posterior burns more likely to develop PAS