No Light Perception Vision in Neuro-Ophthalmology Practice

Original Contribution Section Editors: Clare Fraser, MD Susan Mollan, MD No Light Perception Vision in Neuro-Ophthalmology Practice Anubhav Garg, BScH, Edward Margolin, MD, Jonathan A. Micieli, MD Background: To determine differential diagnosis and visual outcomes of patients with no light perception (NLP) vision related to neuro-ophthalmic conditions. Methods: Retrospective case series of patients seen at tertiary neuro-ophthalmology practices. Patients were included if they had NLP vision any time during their clinical course. Outcome measures were final diagnosis, treatment, and visual outcome. Results: Seventy-two eyes of 65 patients were included. The average age was 57.6 (range 18–93) years, and 58% were women. The Most common diagnosis (21 patients) was compressive optic neuropathy (CON) with meningioma being the most common culprit (12). Other diagnoses included optic neuritis (ON) (11 patients), infiltrative optic neuropathies (8), posterior ischemic optic neuropathy (7), nonarteritic anterior ischemic optic neuropathy (4), arteritic anterior ischemic optic neuropathy (3), ophthalmic artery occlusion (3), nonorganic vision loss (3), radiation-induced optic neuropathy (2), cortical vision loss (1), retinitis pigmentosa with optic disc drusen (1), and infectious optic neuropathy (1). Ten patients recovered vision: 7 ON, 2 infiltrative optic neuropathy, and 1 CON. Corticosteroids accelerated vision recovery in 7 of the 11 patients with ON to mean 20/60 (0.48 logMAR) over 9.0 ± 8.6 follow-up months. Eleven patients deteriorated to NLP after presenting with at least LP; their diagnoses included CON (3), ophthalmic artery occlusion (2), infiltration (2), ON (1), posterior ischemic optic neuropathy (1), arteritic anterior ischemic optic neuropathy (1), and radiation-induced optic neuropathy (1). Conclusions: NLP vision may occur because of various diagnoses. Vision recovery was mainly seen in patients with ON. Serious systemic conditions may present or relapse with NLP vision, which clinicians should con- Faculty of Medicine (AG), University of Toronto, Toronto, Canada; Department of Ophthalmology and Vision Sciences (EM, JAM), University of Toronto, Toronto, Canada; Division of Neurology (EM, JAM), Department of Medicine (JAM), University of Toronto, Toronto, Canada; and Kensington Vision and Research Centre, University of Toronto, Toronto, Canada. The authors report no conflicts of interest. Address correspondence to Jonathan A. Micieli, MD, Kensington Vision and Research Centre, 340 College Street, Suite 501, Toronto, ON, Canada, M5T 3A9; E-mail: [e-mail] Garg et al: J Neuro-Ophthalmol 2022; 42: e225-e229 sider as an alarming sign in patients with known malignancies. Journal of Neuro-Ophthalmology 2022;42:e225–e229 doi: 10.1097/WNO.0000000000001340 © 2021 by North American Neuro-Ophthalmology Society T he inability to detect light, known as no light perception (NLP), is the most severe form of vision loss and typically signals an aggressive or end-stage disease process because all afferent input from the eye is lost. NLP vision may be caused by various disease processes and localize to the retina, optic nerve, chiasm, or bilateral involvement of the retrochiasmal visual pathways. These conditions may not only have a dramatic impact on vision but may also be the first presentation of life-threatening conditions. No previous study has systemically looked at this patient group, although NLP vision has been described in the context of many causes including vasculitides such as giant cell arteritis (GCA) (1,2), neuromyelitis optica spectrum disorder (NMOSD) (3), multiple sclerosis (4), compressive optic neuropathies (CON) from lesions such as pituitary macroadenomas or meningiomas (5), traumatic optic neuropathy (TON) (6), infectious processes such as herpes zoster ophthalmicus (7), and infiltration from leukemia (8) or lymphoma (9). NLP vision may be reversible with prompt treatment and sometimes visual function can be restored to normal level. Previous case reports and series have described recovery from NLP vision in patients with varying etiology including GCA (10,11), optic neuritis (ON) (12) due to NMOSD (3), CON (13), TON (14), and herpes zoster–related optic neuropathy (15). The goal of this study was to determine the differential diagnosis of NLP vision in neuro-ophthalmology practice. We also aimed to discern which cases can be reversible and which represent systemic life-threatening conditions. METHODS This was a retrospective review of consecutive patients presenting to tertiary neuro-ophthalmology practices at the University of Toronto with NLP vision. The University of e225 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution Toronto Research Ethics Board approval was obtained. Patients were included if they had a documented visual acuity of NLP in one or both eyes at any point during their clinical care. As is routine in our practices, NLP was determined by presenting a bright light approximately 10 cm from the patient’s eye with the fellow eye completely occluded. The patient was then asked whether they were able to perceive any light in the eye. Patients with general ophthalmology conditions including end-stage glaucoma, retinal detachment, or traumatic open globe injuries were excluded. All patients were evaluated in a standardized fashion by the same 2 neuro-ophthalmologists (E.M. and J.A.M.) over the study period. The neuro-ophthalmic evaluation included Snellen visual acuity, pupillary examination, formal visual field testing (Humphrey 24-2 SITA-Fast), OCT of retinal nerve fiber layer (RNFL), and ganglion cell– inner plexiform layer (GCIPL). Snellen visual acuity was converted to logMAR for analysis in the non-NLP eye. Formal automated visual fields were reviewed for all patients, and the mean deviation (MD) was recorded. The average OCT RNFL and GCIPL thickness were also recorded. The final diagnosis, treatment plan, and final visual outcome were retrieved. NLP vision was considered acute if it occurred within 1 month, subacute if it occurred between 1 and 3 months, and chronic if it occurred beyond 3 months from the initial neuro-ophthalmology visit. All data were exported into Microsoft Excel, and data analysis was performed with the same program. The results were reported as the mean ± SD. RESULTS A total of 72 eyes of 65 patients with NLP vision were included in the study. Seven patients (10.8%) had NLP in both eyes, and 58 patients (89.2%) had NLP vision in one eye. The average age was 57.6 ± 17.9 (range 18–93) years. Thirty-eight (58%) were women. Fifty-four patients had NLP vision at initial presentation, whereas 11 patients developed NLP later during their clinical course. Thirtyone patients (47.7%) developed NLP acutely (within 1 month of their initial neuro-ophthalmology visit), whereas 4 (6.2%) were subacute (within 1–3 months) and 28 (43.1%) were chronic (beyond 3 months). Two patients had an uncertain onset of NLP vision due to cognitive issues. Most patients were referred by ophthalmologists (29/65; 45%), whereas 10 were referred by an emergency physician, 9 by a neurologist, 5 by an optometrist, 4 by a neurosurgeon, and 8 by all other specialties. In 58 patients who had unilateral NLP vision, the average visual acuity in the fellow eye was Snellen 20/45 (range 20/20 to LP) or 0.35 ± 0.60 logMAR (range 0–2.8) and average automated MD, available for 51 eyes, was 211.32 ± 10.68 dB. In the 48 eyes with average RNFL thickness available, the mean was 88.2 ± 52.7 mm. The final diagnosis in patients with unilateral or bilateral NLP vision was categorized as given in Table 1. Three patients with NLP vision were found to have nonorganic vision loss as there was no relative afferent pupillary defect, ability to read the Snellen chart with fogging of the fellow eye, and a positive optokinetic nystagmus response in the affected eye. The causes of CON, ON, and infiltration are summarized in Table 2. Two patients died during the follow-up period because of metastatic cancer. Treatment was initiated in 43 cases and primarily took the form of corticosteroids in 21, radiation in 8, surgery in 5, ocular hypertension medications in 3, infliximab in 2, bevacizumab in 1, an unknown biologic medication in 1, antibiotics in 1, and panretinal photocoagulation in 1 to prevent ocular sequelae of underlying ischemic process. Twelve eyes of 11 patients deteriorated to NLP vision after their initial neuroophthalmology visit. Their categorized diagnoses are summarized in Table 1. The 3 CON cases were all due to meningioma TABLE 1. Characterization of patients with NLP vision based on diagnosis (n = 65) Diagnosis CON ON Infiltration PION NAION AAION Ophthalmic artery occlusion Radiation-induced optic neuropathy Cortical vision loss Retinitis pigmentosa with optic disc drusen Infectious optic neuropathy Nonorganic vision loss Total 21 11 8 7 4 3 3 2 1 1 1 3 NLP on Presentation Deteriorated to NLP 18 (86%) 10 (91%) 6 (75%) 6 (86%) 4 (100%) 2 (67%) 1 (33%) 1 (50%) 1 (100%) 1 (100%) 1 (100%) 3 (100%) 3 1 2 1 0 1 2 1 0 0 0 0 (14%) (9%) (25%) (14%) (33%) (67%) (50%) Recovered Vision 1 (5%) 7 (64%) 2 (25%) 0 0 0 0 0 0 0 0 0 Bilateral NLP 1 1 0 2 1 0 0 1 1 0 0 0 (5%) (9%) (29%) (25%) (50%) (100%) AAION, arteritic anterior ischemic optic neuropathy; NAION, nonarteritic anterior ischemic optic neuropathy; CON, compressive optic neuropathy; NLP, no light perception; ON, optic neuritis; PION, posterior ischemic optic neuropathy. e226 Garg et al: J Neuro-Ophthalmol 2022; 42: e225-e229 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution TABLE 2. Causes of CON, ON, and infiltration Diagnosis Compressive optic neuropathy (n = 21) Meningioma (12) Pituitary adenoma (3) Metastasis (2) Aneurysm (1) Thyroid orbitopathy (1) Osteomyelitis (1) Craniopharyngioma (1) Optic neuritis (n = 11) Idiopathic (7) AQP4-IgG (2) MOG-IgG (2) Infiltration (n = 8) Carcinoma (3) Glioma (2) Leukemia (1) Melanoma (1) IgG4 disease (1) —one due to tuberculum sellae meningioma, one due to optic nerve sheath meningioma (ONSM), and one due to anterior clinoid process meningioma. Infiltration was due to malignant chiasmal glioma in one case and metastatic carcinoma in the other. The 2 cases that deteriorated because of posterior ischemic optic neuropathy (PION) and arteritic anterior ischemic optic neuropathy were both due to GCA. The ON case was characterized as atypical ON. The patient with radiationinduced optic neuropathy deteriorated to NLP vision bilaterally. Forty-eight patients had at least one follow-up visit, and of these patients, 10 (15.4%) recovered at least some degree of vision from the NLP baseline. The categorization for diagnoses in these 10 patients is summarized in Table 1. Of 7 patients with ON with some vision recovery, 1 had seronegative NMOSD, 1 had MOG-IgG ON, 1 had AQP4-IgG ON, and 4 had ON without a known underlying cause. Infiltration was due to acute lymphocytic leukemia (ALL) in one case and optic nerve glioma (ONG) in the other. The CON case was secondary to tuberculum sellae meningioma. The recovered mean final visual acuity in those 10 eyes was Snellen 20/126 (range 20/20 to LP) or 0.80 ± 0.95 logMAR (range 0–2.8) with an automated MD, available for 8 eyes, of 210.34 ± 8.58 dB. For the patients with ON, final visual acuity was Snellen 20/60 (range 20/20 to 20/250) or 0.48 ± 0.55 logMAR (range 0–1.1) with an automated MD, available for 6 eyes, of 27.50 ± 5.81 dB over 9.0 ± 8.6 months of follow-up. The categorized diagnoses for the 7 patients with bilateral NLP vision are summarized in Table 1. In these patients, the CON case was due to metastatic colon cancer, the ON case was due to AQP4-IgG, PION was due to GCA in one case and was postsurgical in the other, the NAION case was associated with a hypertensive emergency, the cortical vision loss case was due to anoxic brain injury, and the radiationGarg et al: J Neuro-Ophthalmol 2022; 42: e225-e229 induced optic neuropathy case was the only one to deteriorate to bilateral NLP vision rather than presenting with it. CONCLUSIONS NLP vision is a devastating end result of various disease processes. Our case series demonstrated that the most common causes were CON frequently due to meningioma followed by ON and infiltration by various malignancies. Vision outcomes were poor overall with patients with ON accounting for most patients who recovered. Patients with known malignancies were found to have compressive or infiltrative optic neuropathies, emphasizing the need for prompt investigations in these patients. Although vision did not recover in most patients, the fellow eye is at high risk of irreversible vision loss in many of the conditions identified including GCA, malignancies causing optic nerve infiltration, or compressive lesions. Neuro-ophthalmologists play an important role in the diagnosis of these cases, and it is possible that NLP is due to nonorganic vision loss, which should be considered during workup. Many patients were referred by ophthalmologists. Most patients who recovered some vision had ON and most patients with ON recovered some vision making this the cause of NLP vision with the most favorable vision prognosis in our cohort. All patients with ON who recovered vision were treated with corticosteroids, most with intravenous methylprednisolone. This is consistent with previously published data: the ON Treatment Trial (ONTT) found that NLP vision occurred in 3.1% of 448 patients (16). The 14 patients with NLP vision in the ONTT had favorable visual acuity outcomes: 20/20 or better in 3, 20/25–20/40 in 5, 20/50–20/ 190 in 3, and 20/200 or worse in 3 (17). Another large study found NLP vision in 7.9% of 151 patients with ON, with all 12 of their patients recovering some visual function (range CF to 20/20) with corticosteroid therapy (12). Furthermore, there were 2 patients with MOG-IgG ON and 2 patients with AQP4-IgG ON in our cohort. Only one of the 2 patients with MOG-IgG ON recovered visual function (from NLP to 20/20), whereas vision did not improve in the other one. A study of 18 eyes of 10 patients with MOG-IgG ON observed NLP vision in 6 eyes of 3 patients at nadir of the worst attack, with all 6 eyes demonstrating some vision recovery (range 20/ 126 to 20/200) with high-dose intravenous methylprednisolone (18). Visual acuity data were only available for one of our patient with AQP4-IgG ON, who also recovered some visual function from NLP to 20/250. A study on AQP4-IgG ON observed residual NLP vision in 2 of 3 patients, indicating that this is the cause of ON with worst visual prognosis (19). Although corticosteroids are classically believed to hasten visual recovery in ON, they are needed in atypical cases such as those caused by AQP4-IgG. CON was the most common etiology of NLP vision in our cohort. It was associated with poor final visual outcomes because 3 patients deteriorated to NLP after initial e227 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution presentation and only 1 patient recovered vision. CON secondary to tuberculum sellae meningioma was the underlying cause in one patient with some visual recovery who was treated with radiation therapy and had a final visual acuity of counting fingers. A previous study of tuberculum sellae meningiomas found 6 of 86 patients (7%) had NLP vision, all of whom remained NLP after surgical resection (20). One study of patients with ONSM found 6 of 64 patients (9%) had NLP based on a visual field grading scale with no patients recovering vision (21). This was consistent with our cohort because all 3 of our patients with ONSM remained NLP throughout follow-up. In addition, a large study of 97 eyes of 79 patients with NLP vision due to various suprasellar tumors including pituitary adenomas, craniopharyngiomas, meningiomas, and other tumors found that 23 patients (29%) and 27 eyes (28%) recovered some vision after surgical tumor decompression. Specifically, 48% of 44 eyes with pituitary adenoma, 18% of 22 eyes with craniopharyngioma, and 8% of 24 eyes with meningioma recovered vision (5). None of the 3 patients with pituitary adenoma or the 1 patient with craniopharyngioma in our cohort recovered vision despite surgery, although it is possible that we would have observed cases with visual improvement if we had a larger cohort of patients with these diagnoses. GCA was an underlying cause of NLP vision in 6 of the patients in our cohort and no patient recovered vision. A study of 45 patients with biopsy-proven GCA showed that 21% of patients had NLP vision and bilateral visual loss in 54% of patients. Only one patient in that study recovered some vision to LP with corticosteroids (1). Recovery from NLP vision due to GCA is rare, with only a few reported cases in the literature (10,11,22). Thus, GCA is associated with poor prognosis in patients with NLP vision, as seen in our cohort, emphasizing the importance of early diagnosis. The goal of therapy in these cases is to prevent further vision loss and systemic complications. Two of the patients who recovered from NLP vision in our cohort had infiltrative optic neuropathy. One of these patients had ONG and recovered to LP after resection. The other patient had ALL and recovered to 20/20 vision after radiation, intrathecal triple therapy, prednisone, and blinatumomab. There are few instances of ONG or ALL causing NLP vision reported in the literature (8,23–27). In our cohort, lifethreatening conditions producing infiltrating optic neuropathy included leukemia, carcinoma, melanoma, and glioma. Infiltration from conditions such as leukemia can cause various systemic issues due to widespread damage to the bone marrow, gastrointestinal tract, central nervous system, cardiovascular system, and other organs. Clinical manifestations include anemia or thrombocytopenia, portal hypertension or ascites, ulcers, cognitive impairment, and syncope. Ultimately, infiltration may result in organ failure and subsequent death (28). In our patient who died of pancreatic cancer, infiltration resulting in NLP vision from leptomeningeal carcinomatosis was the first sign of widespread disease. This demonstrates that e228 clinicians should consider NLP vision as an alarming sign in patients with known malignancies. Melanopsin-expressing photosensitive retinal ganglion cells (pRGCs) are unique photoreceptor cells located in the inner retina that are intrinsically photosensitive (29). The melanopsinexpressing pRGCs participate in neural systems that contribute to non–image-forming light-induced responses primarily by projecting to the suprachiasmatic nucleus, or circadian pacemaker, which synchronizes the pacemaker to the solar cycle (30). Patients with NLP vision are presumed to have no functioning melanopsin-expressing pRGCs, which has consequences for circadian rhythm and sleep regulation in bilateral cases. A large study comparing patients with NLP and LP vision showed that only 37% of patients with bilateral NLP vision had normal circadian rhythm as opposed to 69% of patients with LP vision (31). Thus, bilateral NLP vision seems to confer a unique physiological state worth investigating. Furthermore, patients who underwent bilateral enucleation of the eyes have been reported to have reduced sleep quality and circadian rhythm disturbance (32). This may be an overlooked issue by ophthalmologists and neuro-ophthalmologists and collaboration with primary care specialists or sleep specialists may be helpful. The strengths of our study included a large cohort of patients with NLP vision and comprehensive neuroophthalmic examination with OCT and visual fields, which allowed us to reliably discern the differential diagnosis of NLP vision. The limitations are its retrospective nature, resulting in incomplete follow-up data for some patients, and small sample size for some individual diagnoses. These issues restricted our ability to draw firm conclusions regarding prognosis for each etiology of NLP vision. In conclusion, patients may present with NLP vision because of a range of underlying causes. The most common reason is CON, particularly due to meningioma. Other common diagnoses to consider on the differential include ON, infiltration, and PION. The visual prognosis after a patient presents with NLP vision is generally poor, but those with ON as the cause are likely to have positive vision outcomes with corticosteroid therapy. Life-threatening causes including carcinoma and leukemia may result in NLP vision and should be considered. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: J.A.M.; b. Acquisition of data: A.G. and J.A.M.; c. Analysis and interpretation of data: A.G. and J.A.M. Category 2: a. Drafting the manuscript: A.G., E.M., and J.A.M.; b. Revising it for intellectual content: A.G., E.M., and J.A.M. Category 3: a. 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