SIGNS AND SYMPTOMS

IOP, ON cupping (11% of normals have a cup to disk ratio > 0.5), or VF defect. Visual function tests show decreased magnocellular function (M-type ganglion cells) as the body ‘‘sacrifices’’ peripheral fibers first. Neuronal cell death (ganglion axon loss) is the end result of glaucoma despite disputed mechanism (mechanical, vascular, etc.). Pathology shows retinal atrophy of ganglion cell and nerve fiber layers (has an intact inner nuclear layer as opposed to ischemic retinopathy, which shows dropout of retinal inner third). Etiology may be from

Ischemia: fluorescein angiogram shows hypoperfusion in glaucoma.

Mechanical: axonal compression with decreased axoplasmic flow.

Apoptosis: programmed cell death with no inflammatory response or trace of the original cell. Theories of apoptosis include excessive glutamate that excessively binds to the ganglion cell and opens calcium channels, leading to cell death (also found in high concentration in the vitreous of glaucoma patients).

Neuroprotection: IOP reduction is the only proven form of neuroprotection. Calcium channel blockers may benefit the 10% of normal tension glaucoma (NTG) patients who progress despite maximum treatment. In animal models, Alphagan may preserve ganglion cells after crush injury to the ON.

EPIDEMIOLOGY Glaucoma is the second leading cause of blindness in the United States (first among African-Americans). Types of glaucoma in the United States: POAG (80%), secondary open-angle glaucoma (3%), angle closure (5%), congenital (< 1%), and glaucoma suspects (11%). Prevalence: Caucasians (1%), African-Americans (5%). Fifty percent of patients are undiagnosed, and 50% have IOP < 22 mmHg on first visit. About 4% of Caucasian patients and 8% of African-American patients are blind in both eyes (OU) from glaucoma, defined as VA < 20/200 in the better eye or VF < 20 degrees by Goldmann III4e.

Signs and Symptoms

BLOOD IN SCHLEMM’S CANAL ON GONIOSCOPY (See red line just posterior to the pigmented posterior TM.) Caused by increased EVP (Sturge-Weber syndrome, arteriovenous fistula, carotid–cavernous sinus fistula, pressure from large gonioscopy prism such as Goldmann, superior vena cava obstruction), hypotony, and thyroid eye disease.

CASE PRESENTATIONS Glaucoma in a young myopic athletic male: pigment dispersion syndrome (PDS). Elderly white female (or Asian patient) hyperope with cataract and high eye pressure: relative pupillary

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block (RPB). Glaucoma in an elderly Norweigan male with hairy ears: pseudoexfoliative glaucoma (PXG).

HYPOTONY Resulting from either decreased aqueous production (pthisis, beta-blockers, carbonic anhydrase inhibitors, postoperative, ocular ischemic syndrome, etc.) or increased outflow (rhegmatogenous retinal detachment, cyclodialysis cleft, wound leak, filtering bleb, etc.).

INFERIOR ANGLE PECULARITIES Most metabolically active, most open, most pigmented (posterior TM more active than anterior), and has the most iris processes.

IRIDODONESIS (excessive iris movement) Seen with zonular dialysis, lens dislocation, trauma, pseudoexfoliation syndrome (PXS), and myopia.

IRIS PIGMENT ABNORMALITY Seen with iris nevus, Fuchs’ HIC, glaucomatocyclitic crisis, hemangioma, neurofibroma, and siderosis or chalcosis.

IRREGULAR ANGLE NARROWING Seen with subacute angle closure or RPB, lens dislocation, iris cysts, and PAS (angle narrowing at 12 o’clock is normal).

IRREGULAR ANGLE WIDENING Seen with angle recession, lens dislocation, and cyclodialysis.

IRREGULAR IRIS Seen with lens dislocation, iris cyst or tumor, and segmental atrophy (HZV, surgical trauma, or previous episodes of acute glaucoma).

‘‘LYTIC’’ GLAUCOMAS All involve macrophages that ingest a product and obstruct the TM, such as phacolytic (high-molecular-weight lens protein), melanolytic (pigment breakdown from melanoma), and hemolytic glaucoma (red blood cells [RBCs]).

PIGMENT SPRINKLING Seen with PDS, PXS, melanoma, iris or CB cysts, uveitis, trauma, and IOLs.

SAMPAOLESIS’S LINE (pigment deposition along Schwalbe’s ring or peripheral cornea) Seen classically with PXS, PDS, and other pigment sprinkling syndromes.

SCLERAL SPUR CHARACTERISTICS Visible (angle open), hidden (uveal meshwork commonly seen nasally, narrow angle, angle closure or synechia, inflammatory precipitates or exudates commonly seen inferiorly), prominent, and white (torn uveal meshwork, torn ciliary muscle, cyclodialysis cleft).

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TM PIGMENTATION Increases with age and seen with PDS (‘‘black crayon’’ appearance), PXS (‘‘brown sugar’’ appearance), uveitis, trauma (including post-LPI or surgery), hyphema (pigment ‘‘balls’’ inferiorly), melanoma, and Sampaolesis’s line.

Exam and Imaging

EXAM, ANTERIOR CHAMBER EVALUATION Van Herick grading measures peripheral AC depth compared with corneal thickness at the temporal limbus, with a slit lamp beam slightly off-center. If AC depth is equivalent to corneal thickness, then the angle is likely to be open (usually equivalent to Shaffer grade IV); if AC depth is one-quarter cornea thickness, then the angle is most likely occludable (grade II and consider a LPI). Risks of a persistent shallow chamber include increased AC inflammation, increased fibrin, and PAS (can form within 7 to 10 days).

EXAM, GONIOSCOPY Gonio prisms are needed to see into the angle because of total internal reflection. May give either a direct view (e.g., Koeppe) or an indirect view, which gives an inverted image of the opposite angle (e.g., Zeiss, Posner, Sussman, and Goldmann).

Iris contour and width: open 45 degrees, narrow 10–20 degrees (hyperopes). Can also grade as 1þ convex (normal), 3þ convex (hyperopia, angle closure, or RPB), flat (myopia, aphakia, pseudophakia, or plateau iris), or concave (pigment dispersion, cyclitic membrane, PAS in aphakia, or pseudophakia).

Ciliary band (anterior face of ciliary body): look for widened ciliary body, indicating angle recession with broken iris processes.

Scleral spur: an extension of the sclera where the longitudinal ciliary muscle inserts. The angle is open if the spur is visible. May be pathologically dehisced with trauma, called a cyclodialysis cleft, seen as a white band or ‘‘fish mouth’’ behind the scleral spur (looking at the white sclera into the suprachoroidal space); may have hypotony and a retrodisplaced iris root.

Corneoscleral TM: from scleral spur to Schwalbe’s ring, posterior three fifths more pigmented and active; look for synechiae (uveal meshwork).

Angle blood vessels: normal vessels include circumferential loops of the major arterial arcade up to the scleral spur (if cross, scleral spur is most likely abnormal) and short vertical vessels from the anterior ciliary or radial vessel from the iris. Abnormal vessels include vertical vessels that cross the scleral spur and arborize over the TM. Neovascularization shows a flat table-top iris surface and fibrovascular membrane with a red hue, from aqueous VEGF draining through the TM.

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EXAM, GONIOSCOPY GRADING SYSTEMS

Becker goniogram: two concentric circles are drawn, representing Schwalbe’s ring and the scleral spur; angle pathology can be illustrated easily on the diagram.

Shaffer: most commonly used grading system; grades the angle of iris insertion with the plane of TM: grade IV, wide-open 45 degree angle, CB is seen, closure not possible; grade III, open angle up to 35 degrees, scleral spur is seen; grade II, 20 degree angle, only TM is seen and angle closure is possible; grade I, 10 degree angle, only Schwalbe’s ring

or bare TM is seen and closure is probable; and grade 0, the angle is closed. Iris insertion is graded A–D, from posterior to anterior. In reality, most people use a modified Shaffer system.

Scheie: grade I–IV, opposite of Shaffer grading system (grade IV is closed, and grade I is open to the scleral spur).

Spaeth: four variables. 1. Iris insertion: A (anterior insertion, equal to

Shaffer grade D), B, C, D (equal to Shaffer grade A), or E (posterior insertion, angle recession). 2. Estimated angle degree from 0 to 50%. 3. Iris configuration graded Q , R, or S (Queer ¼ concave, as in reverse pupillary block; Regular ¼ flat; or Steep ¼ 3þ convex). 4. TM pigmentation graded from 0 to 4þ. For example, D30R is normal.

IMAGING Stereo photographs are able to provide reliable documentation of glaucomatous optic neuropathy.

GDx: a scanning laser polarimeter that estimates retinal nerve fiber layer thickness through measurement of a polarized laser light passing through the naturally birefringent nerve fiber layer and cornea. The orderly arrangement of microtubules within the axons and the arcuate bundles of nerve fibers separated by Mu¨ller’s cells creates birefringence and thus polarizes light in phase and retards light that is out of phase.

The GDx machine plots the NFL retardation along two rings 10 degrees apart around the ON. The graphical printout divides the nerve into four quadrants and averages 1500 points in each quadrant (excluding NFL overlying retinal blood vessels). Colors indicate NFL thickness, and red-orange warm colors represent more retardation and thus a thicker NFL (usually superior and inferior); the cool blue colors indicate less retardation and a thinner NFL.

One problem is confounding birefringence from the corneal stroma and lens. Corneal polarization is usually 20 degrees down and nasal, which is adjusted for by the GDx machine. However, some people have different corneal orientation and thus may have false negative reading, with usually a nasal or temporally shifted red colors.

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Optical coherence tomography (OCT) and retinal thickness analyzer (RTA) are able to image the optic nerve with high resolution. They are analogous to an ultrasound but use light instead of sound, and may be used as adjuncts for glaucoma diagnosis.

INTRAOCULAR PRESSURE (IOP) SCREENING IOP screening has very low sensitivity and specificity for POAG. Mean pressure is 16 mmHg and is nongaussian and skewed toward higher IOPs.

Schiotz: tests ocular rigidity. High rigidity gives a falsely high IOP, as seen with high hyperopia, long-standing glaucoma, age-related macular degeneration, and vasoconstrictors. Low rigidity gives a falsely low IOP, as seen with high myopia, miotics, RD or any ocular surgery, intravitreal gas, and thyroid disease. Problems include increased IOP from the instrument indentation. The principle behind the Schiotz test assumes that all eyes respond in the same way.

Goldmann applanation: based on the Imbert-Fick principle (Ppressure ¼

Fforce / Aarea) and is equivalent to the force required to overcome the resistance of the capillary action of tears and flatten a 3.06 mm2 area of cornea (the area of the applanation tip; could have been 2–4 mm2, but 3.06 allows the scale reading in grams 10 ¼ IOP). Biprism splits image, allowing Vernier acuity to estimate IOP. Astigmatism (4 D ¼ 1 mmHg) has average horizontal and vertical readings.

IOP is overestimated by thick semicircles and corneas (except corneal edema underestimates) and globe pressue (squeezing, thyroid restrictive >6 mmHg increase in upgaze). A significant percentage of ocular hypertension (OHT) patients have thick corneas.

IOP is underestimated by thin corneas (e.g., following PRK) or fluid under a LASIK flap.

Perkins: applanation like Goldmann.

Tonopen: applanation and indentation; overestimates low IOP, underestimates high IOP. Similar to MacKay-Marg tonometry.

Others: manometry only true measure of IOP. Pneumotonometer is least affected by corneal thinning (good after refractive surgery). Noncontact air-jet is unreliable with glaucoma. Tonography measures facility by Schiotz over 4 minutes.

OPTIC NERVE EVALUATION ON assessment is the most important factor in glaucoma diagnosis; it is objective, unlike VF testing.

Most important diagnostic signs: vertical elongation of cup (in only 10% of normals; usually horizontal) or asymmetric cupping (difference in cup to disk ratio < 0.2 is seen in only 1% of normal individuals), rim notching or thinning, disk hemorrhage, and no rim pallor.

Axonal loss: with modest damage, usually NFL loss is at the inferotemporal rim (leading site of most damage; thus, a superior

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nasal step or arcuate VF defect is the most common specific VF finding). With moderate damage, the temporal rim may show prominent loss, and advanced damage may leave only a remnant of the nasal rim. No axons cross the horizontal midline; thus, glaucomatous defects respect the horizontal visual field.

Drance hemorrhage (splinter hemorrhage of the NFL on or near the disk): most frequently seen with NTG and is a strong risk factor for progression of glaucoma (4–5 increased risk of VF loss when present; glaucoma progresses in 71% of patients vs. 33% without hemorrhage; POAG patients are 14 more likely to progress during the year after hemorrhage diagnosed than are patients without Drance hemorrhage). Prevalent in one third of

NTG patients, one tenth of POAG, and one hundredth of normals (usually from posterior vitreous detachment, diabetes, hypertension, papillitis, or AION). Prevalence increases with severity of glaucoma but decreases with very advanced disease. Usually inferotemporal location and transient (average resolution in 10 weeks) but recurrent in two thirds of patients. Mechanism: microinfarcts, microvenous occlusion, and mechanical rupture.

Less specific signs: peripapillary atrophy (PPA), baring of a circumlinear disk vessel, angulated vessel at disk margin (bayoneting), laminar dots of the cribriform plate, focal arteriolar narrowing in severely damaged eyes, overpass phenomenon, NFL defects, acquired ON pit, and saucerization (difficult to distinguish where the cup starts and the rim ends).

Cupping: not as important as the health of the neural rim. Can lose up to 50% of axons before clinical glaucomatous changes are seen. Sixty-six percent of normal patients have a C:D <0.3, and only 6% of normal patients are >0.5 (this latter group is disproportionately referred to ophthalmology). C:D ratio is larger in African-American patients. Cupping may be reversible in children, increases with age, and is larger when seen in stereo.

PPA: beta zone atrophy is more prevalent in glaucoma and shows marked RPE and choriocapillaris atrophy closer to the disk (present in only 20% of normal patients); alpha zone atrophy is seen in almost all normal eyes and shows irregular hypoor hyperpigmentation.

Nerve fiber layer analysis: best seen with high magnification, high illumination, and a red-free filter. Light is normally reflected by the NFL and RPE; however, red-free light eliminates the RPE reflection and allows better NFL visualization. Often see a grainy appearance from Mu¨ller cell processes. Brighter and whiter reflection indicates a thicker NFL obscuring the underlying vessels. A

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NFL defect may precede a glaucomatous VF defect; may see diffuse atrophy versus wedge-shaped defect.

Other presentations: young patients with high IOP may show diffuse cupping with regular thinning. Focal glaucoma, usually in females with vasospastic risk factors (migraine, Raynaud’s phenomenon, etc.), may show very localized rim loss usually inferiorly. Senile sclerotic glaucoma is often seen in older patients with hypertension or ischemic coronary artery disease and may show marked PPA, sloped cup, and pale rim (saucerization).

PERIMETRY, NORMAL AND ABNORMAL VISUAL FIELDS The visual field can be pictured as ‘‘a hill of vision in a sea of darkness.’’

Normal VF: 50 to 60 degrees superiorly, 60 degrees nasally, 70 to 75 degrees inferiorly, and 90 to 100 degrees temporally. The normal blind spot is 15 degrees temporal to fixation and is 6 degrees wide 8 degrees high. The temporal VF does not necessarily respect the horizontal meridian.

Glaucomatous VF defects: represent nerve fiber bundle defects. The ganglion cell layer and glaucomatous damage respect the horizontal meridian (vs. chiasm and posterior defects, which respect the vertical midline; thus, if VF defect respects the vertical midline, consider neuroimaging). Ninety percent of early glaucomatous damage is in the central 30 degrees.

Arcuate defect: within 10 to 20 degrees of fixation; most common and earliest finding in glaucoma.

Bjerrum’s scotoma: complete arc from blind spot to the horizontal meridian

Seidel’s scotoma: proximal small comma-like arcuate scotoma off the blind spot

Central island: superior and inferior Bjerrum’s scotoma

Nasal step: relative depression of a horizontal hemifield; may be generalized nasal or binasal depression

Paracentral scotoma: <10 degrees of fixation; for example, a Derringer scotoma connects a paracentral scotoma with the blind spot.

Temporal wedge: from the blind spot extending temporally, wedge shape pointing toward blind spot; represents nasal disk loss (uncommon).

Altitudinal defect: advanced glaucoma

PERIMETRY, MEASUREMENT A decibel is a relative log unit of scale. By convention, the brightest light generated by the perimeter machine is 0 dB; thus, a light that is 1 log order of magnitude dimmer than the brightest light is 10 dB.

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Frequency-doubling technology (FDT): beneficial in glaucoma diagnosis, as it differentiates selective magnocellular axon loss based on testing modulation. Looks at temporal modulation, spatial frequency, and contrast sensitivity.

Goldmann perimetry: kinetic perimetry (stimulus size and intensity are constant and moved in the field until seen). The stimuli used to plot an

isopter are identified by a roman numeral, a number, and a letter.

each size increment equals a 2 increase in diameter and a 4 increase in area.

Stimulus intensity is noted by a number from 1 to 4 and a letter from a to e. A change of one number represents a 5 dB (0.5 log unit) change in intensity, and each letter represents a 1 dB (0.1 log unit) change in intensity. Thus, 4e ¼ 1000 apostilbs (brightest); each number below 4 indicates 5 dB decrease, and each letter before e is a 1 dB decrease.

Humphrey visual field (HVF): automated threshold (stimulus seen and missed 50% of the time, suprathreshold 95% chance that stimulus is seen). When reading the printout, ensure correct patient and prescription, then look at gray scale, glaucoma hemifield test (GHT), and global indices. Next, look at the pattern deviation, and check that three

nonedge points >5 dB and one is at least 10 dB.

Full threshold: seen stimulus is presented 4 dB dimmer until not seen (infrathreshold), then brightened by 2 dB until seen (suprathreshold), then bracketed, crossing the threshold point twice in 2 dB increments.

FASTPAC: uses 3 dB increments and only single bracketing to find ‘‘threshold.’’ Good for quick screening test but not best for following glaucomatous VF loss. Is up to 40% faster for normal patients, although short-term fluctuation increases up to 25%, and focal loss can be underestimated in glaucoma.

SITA (Swedish interactive thresholding algorithm): uses continuous modeling of the hill of vision to limit test time.

Reliability parameters:

Fixation loss: stimuli presented in blind spot. Low test reliability if >33%.

False-positive error: VF machine generates a noise without a stimulus presented. Low reliability if >20%, usually with an alert, nervous patient.

False-negative error: after retinal sensitivity at a location is established, a brighter stimulus is presented that should be seen if the patient is attentive. Low reliability if >20%, usually in a drowsy patient.

Global indices:

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