• Glaucoma

    Disc hemorrhages can occur in patients with glaucoma and other conditions. In glaucoma patients, disc hemorrhages are markers for a complex vasculopathy that is just beginning to be understood. They are also predictors of progressive glaucomatous disease independent of intraocular pressure (IOP) and other factors. This paper reviews the differential diagnosis of disc hemorrhage, as well as evidence that suggests disc hemorrhages are an important sign in glaucoma. Lastly, it presents new evidence showing primary open-angle glaucoma (POAG) patients with disc hemorrhages have an abnormality in vascular perfusion.

     

    Case Study

    A 68-year-old white man with type 2 diabetes mellitus and a family history of glaucoma presents for a routine exam. Snellen acuity is 20/20 in both eyes, and applanation tensions are 16 mm Hg bilaterally. The exam is remarkable for suspicious optic disc cupping and moderate nonproliferative diabetic retinopathy in both eyes without macula edema. In the left eye, there is a subtle flame-shaped hemorrhage in the superior nasal quadrant of the disc (Figure 1A). Red-free fundus photography confirms the presence of this hemorrhage and fails to show nerve fiber layer defects (Figure 1B). Since there are other flame-shaped hemorrhages and microaneurysms located throughout the posterior pole, it is likely that this disc hemorrhage is related to diabetic retinopathy. For this patient, standard automated perimetry was reliable and normal in both eyes.

    Image Courtesy of Louis R. Pasquale, MD
    Figure 1A. Fundus photograph of the left eye of a 68-year-old male with type 2 diabetes mellitus. Note the flame shaped hemorrhage at the superior nasal aspect of the disc, as well as other flame-shaped and dot-like retinal hemorrhages.

    Image Courtesy of Louis R. Pasquale, MD
    Figure 1B. Red-free fundus photograph of the left eye of the same patient. There is no obvious nerve fiber layer defect, and the hemorrhages in the retina and on the optic nerve are readily apparent.

    Like disc hemorrhages discovered in the context of diabetic retinopathy, disc hemorrhages may be present in patients with hypertensive retinopathy. Finally, disc hemorrhages are occasionally found in symptomatic patients who present with a posterior vitreous detachment. Presumably, the detaching vitreous body avulses a small vessel on the surface of the disc and produces a disc hemorrhage. Of course, since disc hemorrhages are also associated with the glaucomatous process, any patient with a disc hemorrhage and suspicious cupping deserves a glaucoma workup, regardless of the context in which the condition is discovered.

    Disc Hemorrhage and Glaucoma

    The prevalence of disc hemorrhage is low enough that its detection would not be a useful screening tool for glaucoma,1 but serial observation of the same patients over time suggests that many glaucoma patients will ultimately develop them.2 Several clinical trials in which patients were evaluated in a systematic fashion confirm their importance in predicting disease progression among glaucoma subjects with a range of IOP.

    Among the patients enrolled in the untreated arm of the Collaborative Normal Tension Glaucoma Study, the presence of a disc hemorrhage was associated with a 2.7-fold increased risk of disease progression.3 In the Early Manifest Glaucoma Trial in which patients with open-angle glaucoma (OAG) were randomized to treatment with topical betaxolol and argon laser trabeculoplasty or observation, the detection of disc hemorrhage at follow-up visits was positively associated with disease progression.4 Most remarkably, data from the Ocular Hypertension Treatment Study showed that disc hemorrhage was strongly associated with conversion from ocular hypertension to POAG even when controlling for baseline IOP and central corneal thickness. This result is impressive because patients with disc hemorrhage at baseline were excluded from the study, and disc hemorrhage during follow-up occurred in only 123 of 1618 participants, with the majority of disc bleeders not reaching a study endpoint (either definite disc damage or visual field loss).5

    While disc hemorrhages are markers of disease progression, there are no good guidelines for how to manage glaucoma when they are detected. Certainly it is reasonable to reset target IOPs to lower values when they are found and to consider diurnal IOP checks when they are detected in a patient with an IOP near episcleral venous level in order to get a handle on the degree of IOP fluctuation. Although one research group did find that surgical intervention in OAG patients reduced disc hemorrhage frequency,6 there is insufficient evidence that any specific form of treatment impacts natural disease history in POAG patients with disc hemorrhages.

    Another important point to consider is that not every patient with a disc hemorrhage is going to progress rapidly. This is well illustrated by considering the case of a POAG patient with multiple disc hemorrhages in the right eye documented over a 20-year period (Figure 2). At baseline in 1986 the Humphrey visual field test in the right eye was normal. The patient was monitored with annual visual field tests, which were entirely normal until 2006, when a superior paracentral scotoma and inferior nasal depression were detected in the left eye.

    Image Courtesy of Donald Putnoi, MD
    Figure 2. Optic disc photograph of the right eye in 1986 and 2005 of a patient with POAG recurrent disc hemorrhages during a 19-year period. Note the presence of a hemorrhage in the inferior temporal cup in 1986. In 2005, there is some erosion of the inferior neuroretinal rim tissue, as well as hemorrhages at the superior and inferior poles of the disc.  

    Mechanisms of Disc Hemorrhage Development

    While more data would help guide the management of OAG when a disc hemorrhage is detected, an understanding of the mechanisms of disc hemorrhage might provide insight into the disease's etiology. Two recent studies - the Barbados Eye Study and the Early Manifest Glaucoma Trial - confirm that low ocular perfusion pressure (blood pressure minus IOP) is associated with both the development of POAG and progressive glaucomatous optic nerve disease.7, 8

    Direct measurement of blood flow may yield further clues as to how low perfusion pressure may lead to disc damage. A study co-written by this author found that among a small number of relatively young POAG patients with low perfusion pressure, positional change produced an ischemia-reperfusion pattern to directly-measured retinal blood flow.9 For example, a 55-year-old white female subject in this study with POAG had a seated ocular perfusion pressure of 44 mm Hg. Measurements of retinal blood flow in an inferior retinal arteriole branch near the disc margin demonstrated vacillations in blood flow ranging from an increase of 30 percent to a decrease of 50 percent while she was lying down for 30 minutes compared to her baseline seated value (Figure 3). Such changes could produce hemorrhage from lamina cribrosa capillaries during the hyperperfusion phase and optic nerve ischemia during the hypoperfusion phase.

    Image Courtesy of Louis R. Pasquale, MD
    Figure 3. The retinal hemodynamic profile with positional change of a 55-year-old white female with POAG and seated ocular perfusion pressure of 44 mm Hg. The graph shows the percent change in vessel diameter, blood speed and blood flow in an inferior retinal branch arteriole of the left eye compared to baseline as a function of time in minutes. Measurements were taken while the patient was seated, then while lying on her right side (the shaded section) and while seated again.

    Hemodynamic abnormalities in POAG are not limited to the eye, as was demonstrated by Taiwanese researchers who showed a relative failure of vasodilation in the brachial artery after its occlusion for five minutes with a blood pressure cuff set to 250 mm Hg.10

    These ocular hemodynamic studies begin to provide clues regarding which molecular players may be exacting vascular insults on the optic nerve in glaucoma. The discovery of such mediators may lead to new POAG treatments that prevent glaucoma-related disc hemorrhages from forming. Such treatments may be effective at retarding the structural and functional consequences of disc hemorrhages.

    References

    1. Diehl DL, Quigley HA, Miller NR, Sommer A, Burney EN. Prevalence and significance of optic disc hemorrhage in a longitudinal study of glaucoma. Arch Ophthalmol. 1990;108(4):545-550.
    2. Bengtsson B. Characteristics of manifest glaucoma at early stages. Graefes Arch Clin Exp Ophthalmol. 1989;227(3):241-243.
    3. Drance S, Anderson DR, Schulzer M. Risk factors for progression of visual field abnormalities in normal-tension glaucoma. Am J Ophthalmol. 2001;131(6):699-708.
    4. Leske MC, Heijl A, Hussein M, Bengtsson B, Hyman L, Komaroff E. Factors for glaucoma progression and the effect of treatment: the early manifest glaucoma trial. Arch Ophthalmol. 2003;121(1):48-56.
    5. Budenz DL, Anderson DR, Feuer WJ, et al. Detection and prognostic significance of optic disc hemorrhages during the Ocular Hypertension Treatment Study. Ophthalmology. 2006;113(12):2137-2143.
    6. Miyake T, Sawada A, Yamamoto T, Miyake K, Sugiyama K, Kitazawa Y. Incidence of disc hemorrhages in open-angle glaucoma before and after trabeculectomy. J Glaucoma. 2006;15(2):164-171.
    7. Leske MC, Heijl A, Hyman L, Bengtsson B, Dong L, Yang Z. Predictors of long-term progression in the early manifest glaucoma trial. Ophthalmology. 2007;114(11):1965-1972.
    8. Leske MC, Wu SY, Hennis A, Honkanen R, Nemesure B. Risk factors for incident open-angle glaucoma: the Barbados Eye Studies. Ophthalmology. 2008;115(1):85-93.
    9. Feke GT, Pasquale LR. Retinal blood flow response to posture change in glaucoma patients compared with healthy subjects. Ophthalmology. 2008;115(2):246-252.
    10. Su WW, Cheng ST, Ho WJ, Tsay PK, Wu SC, Chang SH. Glaucoma is associated with peripheral vascular endothelial dysfunction. Ophthalmology. 2008;115(7):1173-1178.e1.

    Author Disclosure

    Dr. Pasquale states that he has no financial relationship with the manufacturer of any product discussed in this article or with the manufacturer of any competing product.