history, migraine, and high or low blood pressure, were not confirmed in OHTS to be significant risk factors in the univariate or multivariate analysis. As mentioned previously, black race was found to increase the risk of glaucoma development in the univariate but not in the multivariate analysis, presumably because the increased risk in this population is attributable to the presence of lower CCT and higher cup–disc ratios.

That family history was not identified as a significant risk factor in OHTS is widely thought to be due to inadequate assessment of this information. Clinicians should still consider the patient’s family history when evaluating the patient’s risk of developing glaucoma, if this information is believed to be accurate.

Based on the findings of the examination and the results of OHTS, an assessment of the patient’s risk of developing glaucoma can be derived. The clinician and the patient can decide together whether this risk warrants the inconvenience, cost, and potential side effects of therapy. Care must be taken that the risks and morbidity of therapy do not exceed the risks of the disease. Additional factors that may affect the decision to start ocular hypotensive therapy include the desires of the patient, patient compliance and availability for follow-up visits, reliability of visual fields, and ability to examine the optic disc.

The initial reports from OHTS clearly demonstrated that treatment reduced the risk of progression to glaucoma; however, the incremental structural or functional change that constituted a progression endpoint would not have been associated with the development of symptomatic vision loss. Therefore, the question remained whether delaying treatment was associated with poorer outcomes compared to early initiation of IOP-lowering therapy.

To help answer this question, subjects in the OHTS control arm, after a median of 7.5 years of observation without treatment, received IOP-lowering therapy. Subjects in both groups were monitored for an additional median follow-up period of 5.5 years, during which time all subjects were receiving treatment to lower IOP. At the conclusion of the median follow-up period of 13 years, 16% and 22% of subjects in the initialand late-treatment groups, respectively, progressed. Although the two groups diverged with respect to the development of glaucoma during the original study period (when the observation group did not receive treatment), there was no further divergence in the Kaplan-Meier curves after both groups received IOP-lowering treatment. This result suggests that clinicians may safely consider delaying the treatment of OHT, particularly among patients with a lower risk of conversion to glaucoma.

American Academy of Ophthalmology Glaucoma Panel. Preferred Practice Pattern Guidelines. Primary Open-Angle Glaucoma Suspect. San Francisco: American Academy of Ophthalmology; 2010. Available at: www.aao.org/ppp.

Gordon MO, Beiser JA, Brandt JD, et al. The Ocular Hypertension Treatment Study: baseline factors that predict the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002;120(6):714–720.

Kass MA, Gordon MO, Gao F, et al. Delaying treatment of ocular hypertension: the Ocular Hypertension Treatment Study. Arch Ophthalmol. 2010;128(3):276–287.

Kass MA, Heuer DK, Higginbotham EJ, et al. The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002;120(6):701–713.

Wilson MR, Brandt JD. Update on glaucoma clinical trials. Focal Points: Clinical Modules for Ophthalmologists. American Academy of Ophthalmology; 2003, module 9.

Secondary Open-Angle Glaucoma

Exfoliation Syndrome

Exfoliation syndrome (pseudoexfoliation) is characterized by the deposition of a distinctive fibrillar

Figure 4-3 Exfoliative debris (arrows) collecting on iris processes in inferior anterior chamber angle. (Courtesy of Steven T.

Simmons, MD.)

The chamber angle is often characterized by a trabecular meshwork that is heavily pigmented with brown pigment, usually in a variegated fashion. An inferior pigmented deposition, scalloped in nature, is often present anterior to the Schwalbe line. This pigmented line is often referred to as the Sampaolesi line (Fig 4-4). The chamber angle may be narrow, presumably as a result of the anterior movement of the lens–iris interface, which can occur because of zonular weakness.

Figure 4-4 The Sampaolesi line (arrows) in the inferior anterior chamber angle of a patient with exfoliation syndrome.

(Courtesy of L. J. Katz, MD.)

In addition to the typical deposits and pigmentation, other anterior segment abnormalities are noted. Fine pigment deposits often appear on the iris surface, and peripupillary atrophy with transillumination of the pupillary margin is common. A more scattered, diffuse depigmentation may also occur, with transillumination defects over the entire sphincter region. The pupil often dilates

poorly. Phacodonesis and iridodonesis are not uncommon; they are related to zonular weakness, which may predispose affected eyes to zonular dehiscence, vitreous loss, and other complications (including lens dislocation) during and after cataract surgery (see also BCSC Section 11, Lens and Cataract). Iris angiography has shown abnormalities of the iris vessels with fluorescein leakage.

Exfoliation syndrome may be unilateral or bilateral with varying degrees of asymmetry. Often the disorder is clinically apparent in only 1 eye, although the uninvolved fellow eye often develops the syndrome at a later time. Exfoliation syndrome is associated with OAG in all populations, but the prevalence varies considerably. In Scandinavian countries, exfoliation syndrome accounts for more than 50% of cases of OAG. The odds of the exfoliation syndrome leading to glaucoma vary widely, and range up to 40% over a 10-year period. This syndrome is strongly age-related: it is rarely seen in persons younger than 50 years and occurs most commonly in individuals older than 70 years.

Exfoliation glaucoma differs from POAG in often presenting unilaterally and in showing greater pigmentation of the trabecular meshwork. In addition, the IOP is often higher, with greater diurnal fluctuations than occurs in POAG, and the overall prognosis is worse. Laser trabeculoplasty can be very effective, but the response in exfoliation glaucoma may not last as long as that in POAG. Lens extraction does not alleviate the condition.

Ritch R. Exfoliation syndrome. In: Ritch R, Shields MB, Krupin T, eds. The Glaucomas. 2nd ed. St Louis: Mosby; 1996:993–1022. Schlötzer-Schrehardt U, Naumann GO. Ocular and systemic pseudoexfoliation syndrome. Am J Ophthalmol. 2006;141(5):921–

937.

Thorleifsson G, Magnusson KP, Sulem P, et al. Common sequence variants in the LOXL1 gene confer susceptibility to exfoliation glaucoma. Science. 2007;317(5843):1397–1400.

Pigmentary Glaucoma

The pigment dispersion syndrome consists of pigment deposition on the corneal endothelium in a vertical spindle pattern (Krukenberg spindle; Fig 4-5), in the trabecular meshwork, and on the lens periphery. Typically, peripheral iris transillumination defects are also present. The spindle pattern on the posterior cornea is caused by the aqueous convection currents and subsequent phagocytosis of pigment by the corneal endothelium. The presence of Krukenberg spindles is not absolutely necessary to make the diagnosis of pigment dispersion syndrome, and it may occur in other diseases, such as exfoliation syndrome. Characteristic spokelike loss of the iris pigment epithelium occurs, manifesting as transillumination defects in the iris midperiphery (Fig 4-6). The peripheral iris transillumination defects appear in front of the lens zonular fibers.

Figure 4-5 Krukenberg spindle (arrow). (Courtesy of L. J. Katz, MD.)

Figure 4-6 Classic spokelike iris transillumination defects seen in pigment dispersion syndrome. (Courtesy of Angelo P. Tanna,

MD.)

Gonioscopy reveals a homogeneous, densely pigmented trabecular meshwork with speckled pigment at or anterior to the Schwalbe line (Fig 4-7), often forming a Sampaolesi line. The midperipheral iris is often concave in appearance, bowing posteriorly, toward the zonular fibers. When the eye is dilated, pigment deposits can be seen on the zonular fibers, the anterior hyaloid, and the lens capsule near the equator of the lens (Zentmayer line; Fig 4-8).

Figure 4-7 Characteristic heavy, uniform pigmentation of the trabecular meshwork (arrows) seen in the pigment dispersion syndrome and pigmentary glaucoma. (Courtesy of M. Roy Wilson, MD.)

Figure 4-8 In pigment dispersion syndrome, pigment deposits can be seen on the equatorial region of the lens capsule (Zentmayer line) and on the zonules. (Courtesy of Angelo P. Tanna, MD.)

This syndrome does not universally lead to glaucoma. An individual with pigment dispersion syndrome may never develop elevated IOP, and various studies have suggested that the risk of an affected individual developing glaucoma is approximately 25%–50%. Pigmentary glaucoma occurs most commonly in white males who have myopia and who are between the ages of 20 and 50 years.

Pigmentary glaucoma is characterized by wide fluctuations in IOP, which can exceed 50 mm Hg in untreated eyes. High IOP often occurs when pigment is released into the aqueous humor, such as following exercise or pupillary dilation. Symptoms may include halos, intermittent visual blurring, and ocular pain.

Posterior bowing of the iris with “reverse pupillary block” configuration is noted in many eyes that have pigmentary glaucoma. This iris configuration results in greater contact of the zonular fibers with the posterior iris surface, with subsequent pigment release. Laser iridotomy has been proposed as a means of minimizing posterior bowing of the iris (Fig 4-9). However, its effectiveness in treating pigmentary glaucoma has not been established.