Coronavirus Disease 2019, Eye Pain, Headache, and Beyond.

BACKGROUND: Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), which causes Coronavirus Disease 2019 (COVID-19), emerged in December 2019 and became a devastating pandemic. Although its respiratory effects can be deadly and debilitating, it can lead to other systemic disorders, such as those causing eye pain and headache. This literature review aims to describe presentations of eye pain and headache in relation to COVID-19, with an emphasis on how these disorders help us to understand the pathophysiology of COVID-19. EVIDENCE ACQUISITION: Literature was mined from the PubMed database using the key terms: "eye pain," "conjunctivitis," "episcleritis," "optic neuritis," "migraine," and "headache" in conjunction with "COVID-19" and "SARS-CoV-2." With the exception of general background pathology, articles that predated 2006 were excluded. Case reports, literature reviews, and meta-analyses were all included. Where SARS-CoV-2 research was deficient, pathology of other known viruses was considered. Reports of ocular manifestations of vision loss in the absence of eye pain were excluded. The primary search was conducted in June 2021. RESULTS: The literature search led to a focused review of COVID-19 associated with conjunctivitis, episcleritis, scleritis, optic neuritis, and myelin oligodendrocyte glycoprotein-associated optic neuritis. Four distinct COVID-19-related headache phenotypes were identified and discussed. CONCLUSIONS: Eye pain in the setting of COVID-19 presents as conjunctivitis, episcleritis, scleritis, or optic neuritis. These presentations add to a more complete picture of SARS-CoV-2 viral transmission and mechanism of host infection. Furthermore, eye pain during COVID-19 may provide evidence of hypersensitivity-type reactions, neurovirulence, and incitement of either novel or subclinical autoimmune processes. In addition, investigation of headaches associated with COVID-19 demonstrated 4 distinct phenotypes that follow third edition of the International Classification of Headache Disorders categories: headaches associated with personal protective equipment, migraine, tension-type headaches, and COVID-19-specific headache. Early identification of headache class could assist in predicting the clinical course of disease. Finally, investigation into the COVID-19-associated headache phenotype of those with a history of migraine may have broader implications, adding to a more general understanding of migraine pathology.

Interdisciplinary Protocol for the Management of Vision-Threatening Papilledema.

BACKGROUND: This study evaluates the effectiveness of a multidisciplinary protocol for management of patients with papilledema and vision loss secondary to increased intracranial pressure. METHODS: Retrospective record review of all adult patients who presented with vision-threatening papilledema (VTPE) and were treated under this protocol. Patients are admitted for lumbar drain placement and diuretics and followed daily to determine if they may be managed medically or require surgery (optic nerve sheath fenestration [ONSF] and/or cerebrospinal fluid [CSF] shunting). RESULTS: Nineteen patients were included. Twelve had body mass index in the obese range and 6 were morbidly obese. Fourteen had idiopathic intracranial hypertension. Five had secondary pseudotumor cerebri syndrome related to medication use, dural venous sinus thrombosis, hypothyroidism, end-stage renal disease, pulmonary disease, and diastolic heart failure. Three patients did not require surgery and were discharged on oral diuretics; 3 patients underwent unilateral ONSF, 9 underwent bilateral ONSF, and 4 underwent bilateral ONSF followed by ventriculoperitoneal shunt placement. The average follow-up was 10.1 months. The visual acuity improved bilaterally in 12 patients and unilaterally in 4 patients. The remaining 3 patients had worsened vision in both eyes. Fifteen patients had bilateral improvement in their visual fields. Five eyes in 3 patients showed further constriction of the visual field at follow-up. CONCLUSIONS: We demonstrate how a multidisciplinary complex care protocol for treating VTPE can expedite and streamline treatment and restore vision. We found that most patients had improved symptoms and signs, including visual acuity, visual fields, and papilledema. We encourage institutions that manage VTPE to adopt similar institutional protocols.

Neuro-Ophthalmic Complications in Patients Treated With CTLA-4 and PD-1/PD-L1 Checkpoint Blockade.

BACKGROUND: In recent years, CTLA-4 and PD-1/PD-L1 checkpoint inhibitors have proven to be effective and have become increasingly popular treatment options for metastatic melanoma and other cancers. These agents work by enhancing autologous antitumor immune responses. Immune-related ophthalmologic complications have been reported in association with checkpoint inhibitor use but remain incompletely characterized. This study seeks to investigate and further characterize the neuro-ophthalmic and ocular complications of immune checkpoint blockade treatment. METHODS: A survey was distributed through the secure electronic data collection tool REDCap to neuro-ophthalmology specialists in the North American Neuro-Ophthalmology Society listserv. The study received human subjects approval through the University of California at Los Angeles Institutional Review Board. The survey identified patients sent for neuro-ophthalmic consultation while receiving one or more of a PD-1 inhibitor (pembrolizumab, nivolumab, or cemiplimab); PD-L1 inhibitor (atezolizumab, avelumab, or durvalumab); or the CTLA-4 inhibitor ipilimumab. Thirty-one patients from 14 institutions were identified. Patient demographics, neuro-ophthalmic diagnosis, diagnostic testing, severity, treatment, clinical response, checkpoint inhibitor drug used, and cancer diagnosis was obtained. RESULTS: The checkpoint inhibitors used in these patients included pembrolizumab (12/31), nivolumab (6/31), combined ipilimumab with nivolumab (7/31, one of whom also received pembrolizumab during their course of treatment), durvalumab (3/31), ipilimumab (2/31), and cemiplimab (1/31). Malignant melanoma (16/31) or nonsmall cell lung carcinoma (6/31) were the most common malignancies. The median time between first drug administration and the time of ophthalmological symptom onset was 14.5 weeks. Eleven patients had involvement of the optic nerve, 7 patients had inflammatory orbital or extraocular muscle involvement, 6 patients had ocular involvement from neuromuscular junction dysfunction, 4 patients had cranial nerve palsy, and 4 patients had non neuro-ophthalmic complications. Use of systemic corticosteroids with or without stopping the checkpoint inhibitor resulted in improvement of most patients with optic neuropathy, and variable improvement for the other ophthalmic conditions. CONCLUSION: This study describes the variable neuro-ophthalmic adverse events associated with use of immune checkpoint inhibitors and contributes a more thorough understanding of their clinical presentations and treatment outcomes. We expect this will increase awareness of these drug complications and guide specialists in the care of these patients.