When It's Not Glaucoma

When It’s Not Glaucoma

A variety of conditions can produce visual field defects, OCT findings, optic nerve abnormalities, and nerve fiber layer loss that mimic glaucoma

By Annie Stuart, Contributing Writer

OW OFTEN ARE PATIENTS MISDIAGNOSED WITH GLAUCOMA? “It happens more frequently than you might think,” said Steven D. Vold, HMD, at Vold Vision in Fayetteville, Arkansas. Kimberly Cockerham, MD, FACS, who practices in Stockton, California, agreed. “This is not something I see once in a blue moon. It is fairly common to see a patient who is on glaucoma drops and may not need them.” Whether it’s glaucoma, an intracranial problem (such as pituitary adenoma, meningioma, or carotid or ophthalmic artery aneurysm), or an orbital problem (such as thyroid eye disease or an orbital tumor), certain cases can be a complex challenge for even the most experienced observer. But finding your way through the challenge is essential, as a misdiagnosis may lead to unnecessary testing and treatment. Even worse, it may seriously threaten the patient’s health or vision. Four experts offer guidance for sorting out the differences.

The History Patient histories can offer clues to suggest there’s something other than glaucoma at play. Make sure these clues don’t go unnoticed, said Dr. Cockerham. Among her most baffling cases was a recent referral—a patient who was diagnosed as a “glau­ coma suspect” decades ago and had been on eyedrops ever since. Listen for clues. “He was a good historian,” she said, “but nobody had listened to him.” The patient described being hospitalized after a severe motor vehicle acci­ dent that resulted in a brain abscess. He recalled losing his visual field immediately after the accident and could provide specific details about which areas of his visual field were lost. He had had a completely stable visual field abnormality and optical coherence tomography (OCT) test results for years. Consider age. Consider the patient’s age when taking the history and think about potential causes other than glaucoma, said Dr. Cockerham. “In a young patient, the cause is more likely hereditary, post-traumatic, inflammatory, or infectious. In middle age, compressive conditions and vascular events can occur. In older patients, giant cell arteritis can cause posterior ischemia that results in

© Peter Bollinger © Peter cupping and pallor.”

EYENET MAGAZINE • 41 Nonglaucomatous problems that look like glau­ • Vision loss that came on with a severe headache coma can be asymptomatic. However, 1 common • Double vision clue is sudden vision loss, which is typical of • Temporary graying or blacking out ischemic­ optic neuropathies, but not of glauco­ • Orbital ache or pain ma, said Dr. Vold. In contrast, compressive optic Neurologic symptoms. Ask whether patients neuropathy tends to progress more gradually, have experienced any of the following neurologic confounding the diagnosis. symptoms or problems: Watch symptoms, signs. Other symptoms and • Previous brain trauma or brain problem signs can help you begin to piece together the • Numbness, weakness, or tingling puzzle. The key is asking the right questions about • Headaches, especially those that awaken them vision, as well as asking probing questions about in the morning neurologic symptoms, said Prem S. Subramanian, • A loss of libido MD, PhD, at the University of Colorado Health/ Signs. Although optic disc pallor is a hallmark Sue Anschutz-Rodgers Eye Center in Aurora, of a nonglaucomatous condition, said Dr. Subra­ Colorado. “For example, loss of libido is a cardinal manian, look for other signs like these as well: sign of some pituitary tumors in men, but patients • Proptosis, droopy eyelid, or facial asymmetry often won’t volunteer this information.” • Loss of central visual acuity without a loss of Ocular symptoms. Ask patients whether they peripheral vision have experienced any of the following symptoms: • Central scotoma or visual field that respects the • Sudden or quickly progressing vision loss vertical meridian • Vision that’s different in only 1 eye • Optic nerve pallor • Lack of color vision in 1 eye (red desaturation) • Optic nerves that are symmetric in appearance • Vision loss with eye movement to each other, but 1 visual field is very different

GLAUCOMA PLUS A Case of “Ticks and Fleas on the Same Dog”

A 70-year-old woman was her primary care physi- 1 referred to Dr. Levi’s clinic with cian apparently contin- chronic visual loss. Her medi- ued to refill the drops. cal history included hyperten- Over the next 2-3 years, sion, obstructive sleep apnea, she gradually lost vision well-controlled diabetes, and in the left eye. In 2014 breast cancer that was treated she began to notice in 1999 and was in remission. visual changes in the Her ocular history included right eye and returned laser and cryotherapy in each to the retina specialist who was –11.61, and no responses eye in the 1990s for retinal had seen her in the 1990s. in the left (Fig. 1). There was a holes due to lattice degen- In July 2014, her IOP was left relative afferent pupillary eration. She had cataract 24 mm Hg in each eye. She defect. There was no clinical extraction in her right eye was placed on brinzolamide/ evidence of Horner syndrome. in 2005 and in her left eye in brimonidine drops and was Extraocular movements were 2011. referred for neuro-ophthalmo- full. Trigeminal nerve function, The patient began to notice logical evaluation. including corneal sensation, a cloud in the vision of her left On initial neuro-ophthalmo- was symmetric and normal. eye in 2010. This progressed logical evaluation in August IOP was 14 mm Hg in each over several months. She was 2014, acuity was 20/30 in eye. There was 0.8 cupping told by a glaucoma specialist the right eye and bare light of the right disc with pallor of that she had normal-tension perception in the left. Har- the remaining neuroretinal rim. glaucoma that was worse in dy Rand and Rittler (HRR) The left disc was completely the left eye than the right, color plates was 3/6 in the cupped. Because of the pallor and he started her on latano- right eye. Visual field test- of the neuroretinal rim in both prost. ing showed a dense superior eyes, an MRI scan was done; She was then lost to oph- arcuate defect in the right it showed a large sellar mass thalmological follow-up but eye and the mean deviation with suprasellar extension and

42 • NOVEMBER 2018 • Unilateral or very asymmetric damage movement problems,” she said. • Afferent pupillary defect (APD) “A patient with orbital problems may not be • Color desaturation able to completely move his or her eyes in all • Conjunctival injection or chemosis directions,” added Dr. Cockerham. “Delegating the pupil and motility testing to your technician Ophthalmic Exam: Keep an Open Mind can be a problem.” Above all, be suspicious, said Dr. Cockerham. Testing intraocular pressure (IOP) is obviously “Once a person gets a label of glaucoma, it often important, said Dr. Vold, and if there are concerns doesn’t get challenged, even when the patient ends about optic nerve head disease, additional visual up with a different doctor. The most suspicious fields may be needed. “A thorough vascular eval- diagnosis is unilateral normal-pressure glaucoma uation by an internist may be necessary to rule with an afferent pupillary defect. This is never the out uncontrolled diabetes or hypertension, and a correct diagnosis.” fluorescein angiogram [may be needed] to spot If a patient says they have glaucoma, make sure a previous retinal injury from an old vein occlu­ you agree, said Dr. Subramanian. “If something sion,” he said. ‘smells funny’ or doesn’t quite fit, don’t be afraid Look—with the light on. “The most confusing to question another ophthalmologist’s diagnosis.” patient of all is one with a family history of glau­ A comprehensive ophthalmic exam. To con­ coma, no history of brain issues, and no symp­ firm or rule out a diagnosis of glaucoma, Leah toms whatsoever,” said Dr. Cockerham. If you Levi, MD, at Scripps Health in San Diego, con­ suspect an abnormality, she said, turn on the light ducts a comprehensive ophthalmic exam. to see the patient’s eyes and face more clearly. “This includes checking acuity, color vision, “A lot of eye specialists work in dim rooms, pupils, and visual fields, and looking for eye going from slit lamp to slit lamp,” she said. “We

2 noma. The re- 3 sulting decom- pression of the anterior visual pathways led to improvement of the color vision to 4.5/6 in the right eye. Visual left cavernous sinus invasion field testing in the right eye sion (Fig. 3). The left eye did (Fig. 2). improved; the mean deviation not improve. The patient’s last In September 2014 the in the right eye improved to examination in June 2018 was patient­ underwent subtotal –4.43. In addition, a superior stable as was her MRI scan. resection of the mass, which vertical step was revealed re- She has continued to use the proved to be a pituitary ade- flecting the chiasmal compres- drops in her right eye.

TAKE-HOME LESSONS • More visual field loss than the anterior visual pathways • Patients with glaucoma expected. This patient had can produce cupping that is need to be followed by an more visual field loss than similar to glaucoma, but in ophthalmologist. This patient expected for the degree of these patients the remaining with glaucoma was lost to cupping as well as faster neuroretinal rim will show ophthalmological follow-up progression of visual loss than pallor. The pallor in this case for about 3 years while she expected for glaucoma, sug- indicated that the patient had progressively lost vision, but gesting a nonglaucomatous a chronic nonglaucomatous her primary care physician condition. optic neuropathy in addition continued to prescribe her • Pay attention to pallor. to glaucoma. An MRI scan was glaucoma drops. Uncommonly, compression of therefore indicated.

EYENET MAGAZINE • 43 need to look at these patients in a fully lighted fields of both eyes together, said Dr. Subramanian. room to see if there is asymmetry of the face or “If you don’t look at them side by side, you may globe position or evidence of bilateral involve­ miss a homonymous visual field defect or even ment, like thyroid eye disease.” Other signs to a bitemporal hemianopia. Your brain may fail to watch for? “In a patient with a meningioma, for recognize the pattern if you don’t have both visual example, the temporal aspect of the face overlying fields sitting in front of you at the same time.” the meningioma may get bigger,” she said, “and a Fundus exam. “Over time, we’ve evolved to carotid-cavernous sinus fistula will cause a charac­ the point where people equate optic disc cupping teristic dilation of the vessels on the surface of the to glaucoma,” said Dr. Cockerham. “But it is just eye, and eyelid swelling and proptosis.” 1 of many optic nerve processes that can cause Palpate and measure. If you suspect an orbital cupping.” If the neuroretinal rim has pallor, it’s problem, checking resistance to retropulsion can definitely a red flag that you are not simply deal­ be helpful in detecting a mass or enlarged mus­ ing with glaucoma, said Dr. Levi. “With glaucoma, cles behind the eye, said Dr. Cockerham. This is you may have cupping, but the actual surrounding particularly helpful in Asian patients who do not rim is normal in color and looks healthy.” Spotting become proptotic like other ethnicities. Dr. Levi optic disc pallor is key to preventing a misdiagno­ also recommends measuring whether 1 eye is sis, agreed Dr. Subramanian. more proptotic than the other by using exophthal­ “In addition, with ischemic optic neuropathy, mometry, if available. Taking a photo from above crowded or hypoplastic nerves are more com­ can also be helpful, said Dr. Cockerham. mon,” said Dr. Vold. Visual fields.Any ischemic optic neuropathy OCT. Because optic nerve fiber changes are can produce visual field defects similar to those not specific to glaucoma, OCT won’t be defini­ seen in glaucoma, said Dr. Subramanian. Although tive in differentiating it from nonglaucomatous certain patterns may raise glaucoma red flags, problems, said Dr. Levi, but an OCT scan may be added Dr. Cockerham, visual field defects in a helpful as a baseline for future follow-up. patient with a tumor and another with true glau­ “Because OCT is structural, however, it can coma can be indistinguishable. “There’s nothing provide a very clean delineation along a particu­ that’s pathognomonic.” lar anatomic boundary,” said Dr. Subramanian. In addition, she said, digital perimetry is less “That helps you to say, ‘I’m seeing damage here clear than manual visual fields are in respecting in a more diffuse pattern rather than the typical the vertical meridian and in isolating a cecocentral superior and inferior loss, and that makes me con­ scotoma. “There’s noise in the signal of automated cerned this is something other than glaucoma.’”1 visual fields,” said Dr. Cockerham. “The Hum­ With glaucoma, said Dr. Vold, you’ll typically phrey visual field SITA testing, for example, fills in see inferior rim retinal nerve fiber layer loss before the information in between stimulus points, and you see it anywhere else. “This area is usually this can mute neurologic visual field patterns that affected first, then superior next, nasal third, and are more easily seen when a skilled technician has temporal last,” he said. carefully plotted the Goldmann visual field.” Even though certain patterns may be generally Still, automated visual fields can offer clues. typical for glaucoma, they are not diagnostic, said For example, central loss is indicative of retina or Dr. Levi. For instance, if there is a tumor com­ optic nerve maladies, as opposed to glaucoma, pressing the optic nerve from below, you will also said Dr. Vold. And in normal-tension glaucoma, get inferior RNFL thinning—so this finding is not patients usually don’t have visual acuity loss until specific to glaucoma and can’t be interpreted in later in the disease. isolation of the rest of the clinical picture. “Con­ Whenever possible, it helps to look at visual versely, certain patterns are very atypical for glau­ coma and should raise alarm bells.” These patterns include MEETINGS ON DEMAND AAO Meetings on Demand segmental RNFL thinning allows you to view the Glaucoma Subspecialty Day program due to a loss of signal caused alone or as part of a complete package of all 8 Subspecialty by media opacities, or sec­ Day meetings, the AAOE program, and highlights from AAO toral peripapillary decrease 2018. The latter includes a total of nearly 200 hours and 1,000 in RNFL due to branch presentations, inclusive of both glaucoma and neuro-ophthal- retinal vein occlusion. mology symposia and original pa- In all patients but espe­ per presentations. To learn more, cially those under age 40, Dr. visit aao.org/ondemand. Subramanian also checks the source images for optic disc

44 • NOVEMBER 2018 drusen, which can mimic glaucomatous defects. some glaucoma specialists—are patients who are Specialized imaging. A variety of red flags losing visual fields despite what seems to be good might warrant specialized imaging. Asymmetry control of their IOP. “Much of the time, patients may be one, said Dr. Cockerham, because glau­ referred to me do have glaucoma, however, and I coma does not tend to be an asymmetric process. can ascertain that by careful review of their clini­ The following red flags indicate a nonglaucoma­ cal findings without getting a scan,” she said. tous problem is to blame, rather than glaucoma: If needed, imaging may involve magnetic res­ • The patient has unilateral normal-pressure onance imaging (MRI) or a magnetic resonance glaucoma with an APD, especially if the APD is angiogram or computed tomography (CT) angi­ more than a subtle one. ography. “If you have a high degree of suspicion • The patient has chronic open-angle glaucoma and don’t feel comfortable reviewing these scans,” with an APD, especially if it’s more than subtle. said Dr. Cockerham, “consider referring them to a • The optic nerve is more pale than cupped. neuro-ophthalmologist.” • Visual field loss is progressing more rapidly Dr. Cockerham cited the case of a patient than expected for glaucoma. where this didn’t happen. The patient had been • Visual field loss is progressing despite normal seen by 5 previous eye care providers, but over the IOP or IOP that’s under control. course of 6 months she lost vision in the involved • Severity of cupping doesn’t match the visual eye to no light perception. In this patient, the field defect. noncontrast CT scan of the brain was done in • The OCT of the optic nerve and macula does an emergency department and had been read as not correlate with the visual fields. normal, but an apical mass was visible on 1 digital • The visual fields or macular ganglion cell OCT slice. An MRI with gadolinium revealed a large have a vertical feel to them (homonymous pattern/ orbital apex mass that was found to be steroid- bitemporal/junctional). responsive, but there was no return of vision. • There are signs or symptoms of other nerve 1 Gupta PK et al. Open Neurol J. 2011;5:1-7. involvement, such as double vision or a droopy eyelid. Signs and symptoms in synch? Another way MEET THE EXPERTS to suss out nonglaucoma entities: “When making Kimberly Cockerham, MD, FACS your assessment, don’t rely too heavily on any Orbit-plastics-neuro-ophthal- single particular piece of data and ignore others,” mology specialist in private said Dr. Subramanian. Symptoms and signs need practice in Lodi, Modesto, and to align, emphasized Dr. Vold. Stockton, Calif.; Adjunct Associate For example, it’s important to take note when Clinical Professor at Stanford University, Palo a patient has an elevated IOP and some degree Alto, Calif. Relevant financial disclosures: None. of vision loss—whether central visual acuity or Leah Levi, MD Clinical Professor a visual field abnormality—but the appearance Emerita at the University of Cal- of the optic disc doesn’t quite match, said Dr. ifornia, San Diego; and director Subramanian. of neuro-ophthalmology at the Or, in a patient with a potential pituitary tumor Scripps Clinic Division of Oph- or other compressive lesion of the optic nerve or thalmology in San Diego. Relevant retrochiasmal visual pathway, comparing right financial disclosures: None. and left eyes may reveal clues. “Analyzing the mac­ Prem S. Subramanian, MD, PhD ular ganglion cell complex, you may see a pattern Professor of ophthalmology, of ganglion cell loss that matches the visual field neurology, and neurosurgery defect and can really demonstrate a homonymous and division head of neuro-oph- or bitemporal defect,” he said. Many glaucoma thalmology at the University of specialists do not look at this testing and may Colorado Health/Sue Anschutz-Rodgers miss that the problem is retrochiasmal, added Dr. Eye Center, Aurora, Colo. Relevant financial Cockerham. disclosures: None. Refer to a Neuro-Ophthalmologist Steven D. Vold, MD Glaucoma If the clinical picture is not consistent with the and cataract specialist at Vold degree of “glaucoma” you are seeing, it may be Vision in Fayetteville, Ark. Rele- time to refer to a neuro-ophthalmologist, said Dr. vant financial disclosures: None. Levi. What results in most referrals—and is most For full disclosures, find this article troubling for many general ophthalmologists and at aao.org/eyenet.

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