NEURO- s OPHTHALMIC PRESENTATIONS OF The ocular examination can aid diagnosis and help guide treatment.

BY HANNE GEHLING, BS, AND KIMBERLY M. WINGES, MD

ituitary macroadenomas are benign tumors. The most AT A GLANCE common subtype is clinically

nonfunctioning pituitary s adenomas, which are defined Pituitary macroadenomas are benign tumors that are commonly Pby an absence of clinical evidence of diagnosed as incidental findings on imaging, or patients may present hormonal hypersecretion.1 Patients initially with loss and/or headache. The eye clinic is with pituitary macroadenomas therefore often a patient’s first point of care. may present to an eye clinic with

symptoms related to mass effect on s surrounding structures, which can By understanding the clinical signs associated with pituitary adenomas, include headache, bitemporal visual eye care providers can ensure that a patient with associated visual defects, and ocular motor deficits defects receives an early diagnosis and can provide information that (see Key Ocular Findings in Pituitary Macroadenoma).2-4 helps to guide treatment and set reasonable expectations. If you suspect that a patient has a nonfunctioning pituitary adenoma, the following steps are warranted: visual acuity testing, color plates, pupillary defect, an evaluation of the to narrowing the differential diagnosis, a cranial nerve examination, an optic discs’ appearance, the information gathered by these assessment for a relative afferent testing, and OCT imaging. In addition assessments can guide treatment strategies, predict prognostic factors for recovery, inform providers’ and patients’ expectations, and document KEY OCULAR FINDINGS IN PITUITARY MACROADENOMA postoperative recovery after resection 5 s or radiotherapy. Visual field defects • Superior progressing to complete bitemporal VISUAL FIELD DEFECTS • Junctional (postfixed chiasm or anterior tumor spread) Visual field testing is central to the • Rarely, macular bitemporal hemianopsia or homonymous visual field loss (prefixed chiasm or workup of pituitary adenomas. In a posterior tumor spread)

s review of eight studies, visual field Pituitary apoplexy disturbances were the most common s  symptoms at presentation, found in • Hemifield slide approximately 46% of all patients.4 It is • Cranial nerve palsies, especially multiple important to note, however, that slow s See-saw tumor growth may delay patients’ • Thinning of the binasal macular ganglion cell layer and temporal retinal nerve fiber layer on OCT presentation to an eye clinic, and some • Temporal or bow-tie atrophy of the on examination asymptomatic cases are detected incidentally on screening.

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). Pituitary Hemifield Slide Hemifield ). Second, compression Second, ). Although the underlying 7 7 See-saw nystagmus (SSN) is a rare a is (SSN) nystagmus See-saw Cranial nerve (CN) palsies occur as occur palsies (CN) nerve Cranial OCT imaging is useful for useful is imaging OCT ocular motor syndrome characterized characterized syndrome motor ocular intorsion and elevation of cycle a by synchronous with eye one of the of extorsion and depression in inverted is that scenario a other, patterns Two half-cycle. next the pendular-type The exist. SSN of parasellar of typical more is SSN from differentiated is it and masses, rolling and smooth its by SSN jerk movements. SSN pendular of pathophysiology two-hit a debate, of subject a remains First, proposed. been has hypothesis may chiasm the of compression of error calibration retinal a to lead causing reflex, vestibulo-ocular the (see plane roll the in disturbance a Slide Hemifield OCULOMOTOR DEFICITS DEFICITS OCULOMOTOR the by caused compression of result a the of out tumor a of extension direct cavernousadjacent the into and sella III, CN of palsies Multiple sinuses. this to localize VI and/or V2, V1, IV, several of any with patient A region. diplopia of complain will palsies CN present may cases, severe in and, result a as headache with acutely Acute-onset apoplexy. pituitary of this in headache and diplopia immediate prompt should scenario (see neuroimaging lead to nystagmus in the pitch and pitch the in nystagmus to lead planes. roll OCULAR IMAGING IN DIAGNOSIS AND MANAGEMENT layer fiber nerve retinal the visualizing cell ganglion macular and (RNFL) visual with patients in (GCL) layer of crossover of the remaining visual remaining the of crossover of complete of setting the in field (see hemianopsia or Cajal of nucleus interstitial the of the of nucleus interstitial rostral the fasciculuscan longitudinal medial Pituitary adenomas may also cause also may adenomas Pituitary decompensation to due diplopia lack the by phoria preexisting a of

, a, overlying

chiasm prefixed prefixed

postfixed chiasms postfixed 6 Tilted nerve Atypical opticglaucomatous neuropathy contusion with chiasmal Trauma Hydrocephalus • • • • (generally do not respect vertical vertical (generally do not respect midlines well) Not chiasmal = anomalies nerve anomalies = optic Not chiasmal Other   scotoma due to compression atcompression to due scotoma nerveoptic the of confluence the chiasm. and s s sellae, tuberculum the within gland a as to referred likelymore is adenoma pituitary chiasmposterior the compress to aproduce to tracts optic and hemianopsiabitemporal macular loss.field visual homonymous or Conversely, producemay sellae dorsum the relatedloss field visual of patterns junctionala or nerve optic the to | OCTOBER 2020

6 ). Differential Diagnosis of Bitemporalof Diagnosis Differential Glioma/astrocytoma Demyelinating lesion sarcoid or inflammatoryRarely, lesion Pituitary adenoma Parasellar carotid internal arteryParasellar Tumors may grow asymmetrically,grow may Tumors Bitemporal hemianopsia can occurcan hemianopsia Bitemporal • • • • • • • Extrinsic = compression Extrinsic = chiasmal in origin Intrinsic Figure 1. Binasal macular GCL atrophy mirrors bitemporal hemianopsia in pituitary adenoma chiasm compression. Figure 1. Binasal macular GCL atrophy mirrors bitemporal hemianopsia in pituitary adenoma chiasm compression. Fields are shown overlying their respective eyes on OCT for direct comparison.  

and different configurations of theof configurations different and pituitarythe to relative chiasm optic observedthe to contribute can gland opticthe If presentation. of pattern pituitarythe to anterior sits chiasm as a result of suprasellar growth ofgrowth suprasellar of result a as inferiordirect and lesion pituitary the first,chiasm optic the of compression theto rise give that axons the where crossfield visual temporal superior (see Hemianopsia DIFFERENTIAL DIAGNOSIS OF BITEMPORAL HEMIANOPSIA OF BITEMPORAL DIAGNOSIS DIFFERENTIAL s s Original field and OCT scan courtesy of Randy Kardon, MD, PhD MD, Kardon, Randy of courtesy scan OCT and field Original CATARACT & REFRACTIVE SURGERY TODAY

18 s NEURO-OPHTHALMOLOGY PITUITARY APOPLEXY Pituitary apoplexy is a rare vascular emergency caused by infarction or hemorrhage of the pituitary gland. Although eye care providers are unlikely to see a patient with apoplexy in the clinic, it is important to educate patients with a history of pituitary adenoma about the red flags.1,2 s Sudden changes in vision, especially peripheral visual field loss or diplopia s Abrupt onset of severe thunderclap headache, usually retroorbital s Altered mental status or personality changes from acute changes in cerebral blood flow s Nausea, vomiting, or loss of appetite s Low blood pressure s Hormone insufficiency

1. Albani A, Ferraù F, Angileri FF, et al. Multidisciplinary management of pituitary apoplexy. Int J Endocrinol. 2016;2016:7951536. 2. US National Library of Medicine. Pituitary apoplexy. Medline Plus. Updated August 4, 2020. Accessed August 14, 2020. https://medlineplus.gov/ency/ article/001167.htm

A B

Figure 2. Sagittal midline precontrast T1-weighted MRI showing enlargement of the sella turcica and superior extension of a pituitary macroadenoma (arrow, A). Coronal T1-weighted MRI with contrast showing the stretched and compressed over the mass (arrows, B). field loss from chiasmal compression chiasmal compression, patients (Figure 1). Pituitary adenomas cause with intact RNFL and GCL on OCT compression of the axons from the at diagnosis may have a greater nasal retinal fibers, which correspond potential for recovering optic nerve to the temporal visual fields. This function and visual fields after damage is reflected after weeks to surgical intervention.8 months in binasal macular ganglion cell atrophy and its corresponding MANAGEMENT temporal and then nasal peripapillary MRI with and without contrast RNFL. When the superior and of the brain and/or orbits with inferior RNFL quadrants are relatively attention to the sella is the spared, atrophy with a characteristic recommended medium for bow-tie or band appearance diagnosis (Figure 2). A patient with a eventually occurs.8 confirmed pituitary macroadenoma Recent studies have shown that should be referred to both OCT imaging can provide useful neurosurgery and endocrinology. guidance on treatment strategy. Asymptomatic patients with Because extensive RNFL thinning incidental macroadenomas should and macular GCL thinning indicate receive continued ophthalmologic retrograde atrophy of fibers from surveillance because any new visual NEURO-OPHTHALMOLOGY s

HEMIFIELD SLIDE Diplopia without oculomotor involvement, referred to as hemifield slide, can occur with bitemporal hemianopsia in patients who are experiencing compression of the optic chiasm. This syndrome arises when the eyes no longer share an area of visual field, leading to a loss of binocular fusion in a patient with preexisting phoria. When the eyes move apart from one another in decompensated , the patient may perceive the nasal hemifields overlapping centrally as a central strip. In , intermittent crossing of the eyes may be observed as a central strip of diplopia, causing visual confusion. In decompensated esophoria, the two nasal visual fields may appear to separate, leaving a linear central scotoma.1 Similarly, a vertical phoria may produce a superior or inferior segment of missing or Figure. Hemifield slide can arise from a loss of motor alignment in patients with pituitary adenoma jumbled vision (Figure). by interfering with the binocular visual field. creates an overlapping strip of nasal visual field that causes visual confusion, creates a central strip scotoma, and 1. Abouaf L, Vighetto A, Lebas M. Neuro-ophthalmologic exploration in non-functioning pituitary adenoma. Ann Endocrinol (Paris). 2015;76(3):210-219. results in a superior or inferior segment scotoma and central visual field misalignment.

10 Neurosurgery. 2016;79(4):E530-532. symptoms strongly indicate a need in visual function. Preoperative 6. Winges KM, Jivraj I. Topical diagnosis of visual field loss. In: Prajna NV, for surgical intervention. Although visual field assessments are essential ed. Peyman’s Principles and Practice of Ophthalmology. Jaypee Brothers; there are no established guidelines to estimate visual outcomes after 2018:1599-1628. 7. Woo PY, Takemura S, Cheong AM, et al. Pendular seesaw nystagmus in a for the length of ophthalmologic resection and to set both patients’ patient with a giant pituitary macroadenoma: pathophysiology and the role of follow-up, lesion size and a and providers’ expectations. the accessory optic system. J Neuroophthalmol. 2018;38(1):65-69. progression of visual field defects 8. Abouaf L, Vighetto A, Lebas M. Neuro-ophthalmologic exploration in non- functioning pituitary adenoma. Ann Endocrinol (Paris). 2015;76(3):210-219. should inform decisions regarding CONCLUSION 9. Esposito D, Olsson DS, Ragnarsson O, Buchfelder M, Skoglund T, Johannsson timeline. By understanding the clinical signs G. Non-functioning pituitary adenomas: indications for pituitary surgery and post-surgical management. Pituitary. 2019;22(4):422-434. If secondary associated with pituitary adenomas, 10. Muskens IS, Zamanipoor Najafabadi AH, Briceno V, et al. Visual outcomes to pituitary macroadenoma is you can ensure that patients with after endoscopic endonasal pituitary adenoma resection: a systematic review confirmed or progressive, first-line associated visual defects receive and meta-analysis. Pituitary. 2017;20(5):539–552. treatment is surgical resection an early diagnosis and a thorough with endoscopic or microscopic preoperative assessment. The transsphenoidal surgery.9 information gathered can inform HANNE GEHLING, BS Bromocriptine can be used for treatment plans and better predict n MD Candidate, Oregon Health & Science University, prolactin-secreting adenomas ophthalmologic outcomes after Portland (usually small). Large masses treatment. n n [email protected] may require superior craniotomy n Financial disclosure: None 1. Ntali G, Wass JA. Epidemiology, clinical presentation and diagnosis of non- approaches, whereas gamma functioning pituitary adenomas. Pituitary. 2018;21(2):111-118. knife radiotherapy is reserved for 2. Chen L, White WL, Spetzler RF, Xu B. A prospective study of nonfunctioning KIMBERLY M. WINGES, MD pituitary adenomas: presentation, management, and clinical outcome. n Assistant Chief of Surgery for Clinical Operations, large tumor remnants and the J Neurooncol. 2011;102(1):129-138. management of regrowth after 3. Cury MLCD, Fernandes JC, Machado HR, Elias LL, Moreira AC, de Castro M. VA Portland Health Care System, Oregon surgery.9 In a review of 19 studies Non-functioning pituitary adenomas: clinical feature, laboratorial and imaging n Associate Professor of Ophthalmology assessment, therapeutic management and outcome. Arq Bras Endocrinol and Neurology, Casey Eye Institute, that describe visual outcomes after Metabol. 2009;53(1):31-39. resection, approximately 40% of 4. Molitch ME. Nonfunctioning pituitary tumors and pituitary incidentalomas. Oregon Health & Science University, patients recovered completely, 80% Endocrinol Metab Clin North Am. 2008;37(1):151-171, xi. Portland, Oregon 5. Newman SA, Turbin RE, Bodach ME, et al. Congress of neurological surgeons n showed an overall improvement, and systematic review and evidence-based guideline on pretreatment ophthalmol- [email protected] 2% reported further deterioration ogy evaluation in patients withsuspected nonfunctioning pituitary adenomas. n Financial disclosure: None

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