Transient Bilateral Central Scotoma on Awakening: A Distinct Phenomenon

Transient vision loss can be an alarming symptom owing to potentially serious etiologies such as thromboembolism or giant cell arteritis. Transient monocular vision loss (TVML) on awakening has been recently described as a benign phenomenon (Bouffard et al, 2017). Our objective was to describe the unique phenomenon of transient binocular vision loss (TBVL) on awakening.

Original Contribution Section Editors: Clare Fraser, MD Susan Mollan, MD Transient Bilateral Central Scotoma on Awakening: A Distinct Phenomenon Francisco R. Sanchez Moreno, MD, Sasha A. Mansukhani, MBBS, M. Tariq Bhatti, MD, John J. Chen, MD, PhD Background: Transient vision loss can be an alarming symptom owing to potentially serious etiologies such as thromboembolism or giant cell arteritis. Transient monocular vision loss (TVML) on awakening has been recently described as a benign phenomenon (Bouffard et al, 2017). Our objective was to describe the unique phenomenon of transient binocular vision loss (TBVL) on awakening. Methods: Retrospective observational case series of 5 patients who experienced TBVL on awakening seen in the neuro-ophthalmology clinic at the Mayo Clinic between 2016 and 2020. Patients who described generalized blurred vision and those with monocular transient vision loss were excluded. Results: The median age was 81.4 years (range, 68–92 years), and all were male. Every patient described a stereotyped transient bilateral central scotoma on awakening with slightly irregular borders and mild asymmetry between the 2 eyes lasting between 15 and 90 minutes. Frequency ranged from 3 to 7 times per week, and there was a median of 319 episodes (range, 126–728 episodes) before evaluation in the neuro-ophthalmology clinic. All patients had normal optic nerves, and no plaques were noted in the retinal vessels. All 5 had macular drusen, which were predominantly extrafoveal and mild. Two patients underwent electrophysiology testing, which were both normal on full-field electroretinogram (ERG), but there was blunted central wave forms on multifocal ERG. Two patients underwent dark adaptation testing, which showed both prolong and diminished dark adaptation. Neuroimaging and thromboembolic workup were unrevealing. Conclusions: TBVL is a distinct phenomenon from TMVL on awakening, which has a different demographic and symptomology. The etiology is unclear but seems to be a focal macular process in conjunction with an autoregulatory failure resulting in a supply–demand mismatch during lowlight conditions. Journal of Neuro-Ophthalmology 2023;43:209–213 doi: 10.1097/WNO.0000000000001718 © 2022 by North American Neuro-Ophthalmology Society Departments of Ophthalmology (FRSM, SAM, MTB, JJC) and Neurology (MTB, JJC), Mayo Clinic, Rochester, Minnesota. The authors report no conflicts of interest. Address correspondence to John J. Chen, MD, PhD, Department of Ophthalmology, Mayo Clinic, 200First Street, SW, Rochester, MN 55905; E-mail: [e-mail] Sanchez Moreno et al: J Neuro-Ophthalmol 2023; 43: 209-213 T ransient vision loss (TVL) is an alarming symptom owing to potentially serious etiologies such as thromboembolism or giant cell arteritis. Important clinical information of TVL is the pattern and severity, time of day, circumstances, frequency, and concomitant symptoms experienced during the TVL episode (1). TVL can include complete loss of vision in 1 or both eyes or involve part of the vision as a scotoma. When evaluating a patient with TVL, it is important to differentiate dangerous neuro-ophthalmological etiologies, such as thromboembolic disease and giant cell arteritis, from benign conditions, such as visual aura from migraines (Tandon & Dinkin, 2019). There has been recent literature describing transient monocular vision loss (TMVL) on awakening as a benign phenomenon (2), some of which may even be explained by using smartphones in a dimly lit room (3). Patients with TMVL on awakening are predominantly middle-aged female patients who described complete monocular TVL on awakening. We have recently observed several patients who binocular transient central scotomas on awakening, which seemed to be different from the previously described TMVL. In this article, we reviewed our patients in detail and describe the phenomenon of transient binocular vision loss (TBVL) on awakening, which is a distinct entity from TMVL on awakening with different symptomology and demographics. METHODS Retrospective observational case series of 5 patients with TBVL on awakening seen in the neuro-ophthalmology clinic at Mayo Clinic, Rochester, between 2016 and 2020. Patients were included if there was documented isolated, binocular dimming, scotoma, or vision loss present on waking with resolution over time. Patients with binocular blurred vision (which would suggest ocular surface disease 209 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution or difficulty focusing) and TVML were excluded. All patients underwent complete neuro-ophthalmological examination. Static automated perimetry was performed using the 24-2 and 10-2 programs. Spectral domain optical coherence tomography was also performed to assess the peripapillary retinal nerve fiber layer, ganglion cell–inner plexiform layer, and macular integrity. Full-field electroretinogram (ffERG) and multifocal electroretinogram (mfERG) were performed in 2 patients and were recorded using the International Society for Clinical Electrophysiology of Vision standard techniques under scotopic and photopic conditions. Dark adaptation was performed on 2 patients. RESULTS The median age was 81.4 years (range 68–92 years), and all were male (Table 1). The patients all described stereotyped transient bilateral central scotoma on awakening with slightly irregular borders and mild asymmetry between the 2 eyes lasting between 15 and 90 minutes. The scotomas were reported as being fairly dense, but with some translucency (Fig. 1). When turning on the lights, the scotomas became less pronounced but were still faintly present. Frequency ranged from 3 to 7 times per week, and there was a median of 319 episodes (range, 126–728 episodes) before evaluation in the neuroophthalmology clinic. Although most of these episodes occur on awakening in the morning, some of them occurred while awakening earlier in the night. The scotomas did not occur when laying down supine without sleep. They also did not occur with napping during the day under lighted conditions. All patients denied having any pain during or before noticing the scotomas. The onset of vision loss was bilateral and simultaneous in all cases. All affected eyes had best-corrected visual acuities of 20/25 or better. Pupil examination was normal without a relative afferent pupillary defect. Color vision was normal in all 5 patients on Ishihara testing, and automated perimetry was normal. Four patients were pseudophakic, and 1 patient TABLE 1. Subject demographics, characteristics, and past medical and ophthalmological history Case Age Sex 1 87 M 2 78 M 3 82 M 4 68 M 5 92 M Medical History VA RE/LE 20/20 Hypertension 20/20 Atrial Flutter Supraventricular tachycardia Pseudophakia 20/25 Gastro-esophageal reflux 20/15 Cataract OD Pseudophakia OS 20/20 Stage IA non-Hodgkin 20/20 Lymphoma Atrial fibrillation Obstructive sleep apnea Hyperlipidemia Nonexudative macular degeneration Pseudophakia Pseudoexfoliation glaucoma 20/20 20/20 s/p right Trabeculectomy Retinal drusen Diabetes mellitus type 2 · 15 yr Pseudophakia 20/20 Left 6th CNP Pacemaker for Bradycardia 20/25 Chronic kidney disease IV Supraventricular tachycardia s/p ablation Pseudophakia ERG Normal ffERG; mfERG with diminished central wave forms Normal ffERG; mfERG with diminished central wave forms MR Onset to Most Recent Examination Normal 7 mo Normal 4 mo Normal 2 yr Chronic left cerebellar lacunar infarct 10 mo Left petroclival pontine cistern contrast enhancing partially calcified meningioma 8 mo CNP, cranial nerve palsy; ERG, electroretinogram; FfERG, full-field electroretinogram; LE, left eye; MfERG, multifocal electroretinogram; MR, magnetic resonance; RE, right eye; VA, visual acuity. 210 Sanchez Moreno et al: J Neuro-Ophthalmol 2023; 43: 209-213 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution FIG. 1. Description of the progression of the scotoma throughout the months from onset. The drawings represent how the scotoma has faded throughout the months being the left drawing at onset, middle at 3 months, and the right drawing at a year from onset. was phakic. Anterior chamber was deep and quiet in all patients. Intraocular pressures were normal in all patients. All patients had normal optic disc appearance, and no plaques were noted in the retina. All 5 patients had macular drusen, which were predominantly extrafoveal and mild without the presence of macular edema or subretinal fluid on optic coherence tomography (OCT). In addition, the integrity of subfoveal ellipsoid layer was intact in all patients except for 1 patient who had diffuse reticular drusen. Two patients underwent ERGs, which were normal on full-field ERG but showed blunted central wave forms on mfERG (Fig. 2). Two patients underwent dark adaptation curve, which showed prolonged and diminished dark adaptation (Fig. 2). All patients underwent neuroimaging and thromboembolic workup, which were normal except for an incidental left petroclival pontine cistern meningioma in 1 patient and Sanchez Moreno et al: J Neuro-Ophthalmol 2023; 43: 209-213 the redemonstration of a prior chronic left cerebellar lacunar infarct in 1 patient. There was no significant carotid or vertebral artery stenosis in any of the patients, and no patients had atrial fibrillation, other than a patient who was previously known to have atrial fibrillation and was already on anticoagulation. Two patients underwent 24-hour blood pressure monitoring, which was normal in 1 patient and showed mild nocturnal hypotension in the other, but not in the early morning. CASE REPORT A 78-year-old Caucasian man was experiencing numerous episodes of bilateral simultaneous TVL which occurred on awakening in the morning that had been ongoing for 9 months at the time of evaluation in the neuroophthalmology clinic (patient 2 of Table 1). The scotomas were described as central, crescent-shaped fixed, dark 211 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution FIG. 2. A. Fundus photographs show subtle superior reticular drusen in both eyes (yellow arrows). B. Spectral domain Cirrus OCT demonstrates subtle superior drusen in both eyes (yellow arrows). C. Normal full-field ERG—combined response. D. Normal full-field ERG—scotopic. E. Multifocal ERG with centrally decreased amplitudes. F. Dark adaptation curve demonstrates impaired dark adaptation in both eyes. The patient also had a normal full-field ERG photopic response (not shown). ERG indicates electroretinogram. (black/red) lasting between 30 and 90 minutes affecting both eyes in slightly different positions (Fig. 1). The scotomas were significantly less pronounced when the lights were on but were unaltered with postural changes. There was no other associated symptom during or before the episodes. The visual acuity was 20/25 in the right eye and 20/15 in the left eye. Color vision was preserved (Ishihara 13/13 in both eyes), and pupillary reflex was normal with no relative afferent pupillary defect in either eye. Intraocular pressure was 20 mm Hg in the right eye and 18 mm Hg in the left eye. Slitlamp examination revealed pseudophakia in the left eye and an incipient cataract in the right eye. On dilated fundus examination, the optic discs were normal and there were subtle superior macular drusen. No areas of neovascularization, macular edema, or ischemia were noted in either eye. Automated 10-2 visual fields were full in both eyes. OCT macula disclosed some mild drusen in the superior macula of both eyes. Magnetic resonance (MR) imaging of the brain and angiography of the brain and neck were normal. Holter monitor showed no concerning arrhythmia. Twenty four-hour blood pressure monitoring showed mild nocturnal hypotension, but not on awakening. ffERG was normal, and mfERG showed centrally decreased amplitudes. The dark adaptation curve test was impaired (Fig. 2). 212 DISCUSSION We describe 5 patients who experienced recurrent transient bilateral central scotomas on awakening. Although TVL can be caused by potentially lifethreatening or sight-threatening etiologies, transient bilateral central scotomas on awakening seem to be a benign entity about central nervous system (CNS) pathology. Furthermore, it is likely a distinct entity from the previously described phenomenon of TMVL on awakening (Bouffard et al, 2017), in which 90% were middle-aged female patients who described complete monocular TVL as opposed to our cohort who were all male, older, and reported transient bilateral central scotomas rather than complete vision loss. However, given the small number of patients in our series, it is possible that the phenomenon is the same etiology as TMVL on awakening but with varied presentations. Our cohort of patients was relatively homogeneous: All our patients were older male patients, most had daily episodes on awakening lasting between 15 and 90 minutes with complete recovery. No patients developed permanent vision loss. No patients had transient or permanent neurological events, and none had symptoms of giant cell arteritis. The thromboembolic workup and evaluation for alternative systemic causes in all patients were uniformly negative, including carotid Sanchez Moreno et al: J Neuro-Ophthalmol 2023; 43: 209-213 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution Doppler, Holter monitoring, brain imaging (MRI brain and MRA head/neck), erythrocyte sedimentation rate, C-reactive protein levels, and antiphospholipid antibodies. Although one patient had mild nocturnal hypotension on 24-hour blood pressure monitoring, the blood pressure was normal on awakening and another patient had normal 24-hour blood pressure monitoring. All 5 patients had macular drusen, but most were mild and extrafoveal, and otherwise had no visible abnormalities of the optic nerve or retina, including no subretinal or intraretinal fluid on OCT. Among 2 patients who underwent retinal electrophysiology, the ffERG was normal, whereas the mfERG showed blunting of the central wave forms suggesting a focal macular process. In addition, dark adaptation was delayed and diminished in the 2 patients who were tested, which also suggests a retinal process. These findings were out of proportion to the retinal drusen. The late age of onset may suggest that this could be from a retinal degenerative process. The phenomenon of bilateral central vision loss on awakening has been reported sparingly in the past in some retinal disorders. In a study by Fletcher et al (4), 2 of 134 (1.5%) patients with nonexudative age-related macular degeneration reported transient scotomas on waking from sleep. Patients with central serous chorioretinopathy may report a constant central scotoma that is most prominent in the morning immediately after awakening (Wang et al, Munch, Hasler, Prünte, & Larsen, 2008). The presence of symptoms only on awakening suggests that there must be another contributing physiological factor than retinal disease alone. Most normal individuals have an increase in cortisone on awakening with a 38%–75% increase in levels peaking 30–45 minutes (Wüst et al, 2000). There is also a link between corticosteroid use and central serous retinopathy that might suggest a potential link between cortisone and this phenomenon (5). Another neuroendocrine system correlated with awakening is the sympathetic nervous system, which is paradoxically inversely related to the cortisol awakening response. This could possibly cause transient vasodilation that could possibly contribute to the symptoms on awakening (Hirotsu, Tufik, & Andersen, 2015). Other possible contributors could be changes associated with intrinsic retinal circadian clocks and whole body circadian signals, such as cortisone, although the scotomas did not only occur in the morning hours (6). Sanchez Moreno et al: J Neuro-Ophthalmol 2023; 43: 209-213 The mechanism of TBVL on awakening is likely due to a combination of several factors including a focal maculopathy, an autoregulatory failure of the retrobulbar or retinal vasculature resulting in a supply–demand mismatch, and the possible effects of the cortisol awakening system. In addition, there is high metabolic rate of rods in darkness, which places a strain on the retina and has been hypothesized to potentially worsen retinal disease states, such as diabetic macular edema (7). The occurrence of this phenomenon on awakening rather than with exposure to low illumination at other times of the day may reflect increased retinal metabolic demands after long periods of darkness. The exact etiology remains unclear, but a combination of darkness and sleep seems to be the driving factors. In conclusion, TBVL on awakening is a distinct clinical entity from TMVL on awakening. Recognizing this unique phenomenon will affect clinical management and help avoid costly CNS testing but can suggest an occult largely asymptomatic maculopathy. STATEMENT OF AUTHORSHIP Conception and design: J. J. Chen, F. R. Sanchez Moreno; Acquisition of data: F. R. Sanchez Moreno, S. A. Mansukhani, M. T. Bhatti, J. J. Chen; Analysis and interpretation of data: J. J. Chen, F. R. Sanchez Moreno. Drafting the manuscript: J. J. Chen, F. R. Sanchez Moreno; Revising the manuscript for intellectual content: M. T. Bhatti, J. J. Chen. Final approval of the completed manuscript: J. J. Chen. REFERENCES 1. Kerrison JB, Pollock SC, Biousse V, Newman NJ. Coffee and doughnut maculopathy: a cause of acute central ring scotomas. Br J Ophthalmol. 2000;84:158–164. 2. Bouffard MA, Cornblath WT, Rizzo JF III, Lee MS, DeLott LB, Eggenberger ER, Torun N. Transient monocular vision loss on awakening: a benign amaurotic phenomenon. J Neuroophthalmol. 2017;37:122–125. 3. Alim-Marvasti A, Bi W, Mahroo OA, Barbur JL, Plant GT. Transient smartphone “blindness”. N Engl J Med. 2016;374:2502–2504. 4. Fletcher DC, Schuchard RA, Renninger LW. Patient awareness of binocular central scotoma in age-related macular degeneration. Optom Vis Sci. 2012;89:1395–1398. 5. Carvalho-Recchia CA, Yannuzzi LA, Negrao S, Spaide RF. Corticosteroids and central serous chorioretinopathy. Ophthalmology. 2002;109:1834–1837. 6. Baba K, Ribelayga CP, Michael Iuvone P, Tosini G. The retinal circadian clock and photoreceptor viability. Adv Exp Med Biol. 2018;1074:345–350. 7. Arden GB, Jyothi S, Hogg CH, Lee YF, Sivaprasad S. Regression of early diabetic macular oedema is associated with prevention of dark adaptation. Eye (Lond). 2011;25:1546–1554. 213 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.