One of the primary symptoms of Sjögren’s is dry eye. While there are many potential causes for Sjögren’s dry eye, such as inflammation in the lacrimal (tear-producing) glands that reduces tear production, dysautonomia may also play a role.
As part of Dry Eye Awareness month, we are sharing the expert article below entitled “Understanding the Ocular Health Implications of Dysautonomia in Sjögren’s Disease” written by Dr. Sezen Karakus and Jane Huang, BS.
Dysautonomia, which doctors may also call autonomic dysfunction, occurs when there is an underlying malfunction of the autonomic nervous system (ANS). This malfunction can cause impaired signaling of autonomic nerves and ganglia that relay messages from the brain to the internal organs and tissues.
According to experts, approximately 50% of patients with Sjögren’s experience some form of dysautonomia and the vast majority of patients are underdiagnosed with dysautonomia. In addition to the article below, you can read more about dysautonomia by visiting our Dysautonomia in Sjögren’s blog post.
We’d like to thank Dr. Karakus and Jane Huang, BS for writing this article on ocular health in Sjögren’s and dysautonomia and allowing us to share it with you during Dry Eye Awareness Month.
Understanding the Ocular Health Implications of Dysautonomia in Sjögren’s Disease
By Dr. Sezen Karakus (pictured) and Jane Huang, BS Wilmer Eye Institute John's Hopkins University
To assist with clarification on some of the medical terminology and techniques used, the Foundation also added some “Notes” within the article.
Introduction Dry eye and dry mouth are hallmarks of Sjögren’s disease, originally described by Dr. Henrik Sjögren, an ophthalmologist who noticed a pattern in a group of patients with severe dry eye.1 These patients also experienced dry mouth, as well as generalized joint and muscle pain. The proposed pathogenesis was that inflammatory infiltration of the lacrimal and salivary glands would eventually destroy these glands, causing dry eye and dry mouth.1 Over the years, we have learned that Sjögren’s is a systemic disease that can affect multiple other organs and systems, including the central, peripheral, and autonomic nervous systems, with recent attention given to its impact on the autonomic nervous system.2–4 Dysautonomia is a condition where the autonomic nervous system does not function properly. Given the role of the autonomic nervous system in controlling various bodily functions, autonomic dysfunction may have a more significant impact on someone with Sjögren’s than we currently understand. Recognizing the possible role of dysautonomia in Sjögren’s can help us better understand some of the symptoms patients experience and consider different ways to address them. Here, we discuss the possible role of dysautonomia in ocular health in patients with Sjögren’s and how the presentation may differ from patients manifesting with classical keratoconjunctivitis sicca.
Note
Keratoconjunctivitis sicca is the medical term for dry eye caused by lack of tear production.
Classic Ocular Manifestations of Sjögren’s Classic Sjögren’s ocular findings include reduced tear production, defined as aqueous tear deficiency, and ocular surface epitheliopathy, which is observed as ocular surface staining using vital dyes at the slit lamp.5 Tear production is typically measured by the Schirmer test, with a score of less than 5 mm in either eye adding 1 point toward Sjögren’s disease classification.6 Ocular surface staining is usually graded using the Sjögren’s International Clinical Collaborative Alliance Ocular Staining Score (SICCA OSS) system and is considered significant when the score exceeds 5 out of 12 in either eye.6 Dry eye symptoms often precede a Sjögren’s diagnosis by nearly a decade.7 Therefore, ophthalmologists play a crucial role in facilitating timely diagnosis by conducting a thorough ocular surface assessment.
Note
Ocular surface epitheliopathy is the medical term for damage to the epithelial tissue that covers the front of the cornea, which can lead to pain, redness, poor vision, and permanent damage to the cornea.
Dry Eye Symptoms and Diagnostic Challenges
Dry eye symptoms, however, do not always correlate well with clinical signs, making it essential to conduct a slit lamp examination for accurate diagnosis.8 Patients with severe ocular surface staining may have minimal discomfort, indicating reduced corneal sensation. Corneal nerves, which are small fiber sensory nerves stemming from the ophthalmic branch of the trigeminal nerve (see Figure 1 provided by the Foundation), can be damaged, leading to neurotrophic keratitis.9 If not addressed, epitheliopathy may progress to epithelial defects and corneal ulcers. Corneal sensation is a crucial part of the corneal reflex arc, also known as the blink reflex, which protects the eye from damage. Damage to the corneal nerves can impair this reflex, leading to further complications.
Conversely, some patients may experience severe symptoms disproportionate to their clinical signs. These patients may have no ocular surface staining but severe symptoms of dryness, burning, pain, and light sensitivity due to overly sensitive corneal nerves. This condition, known as “pain without stain,” indicates neuropathic corneal pain or corneal neuralgia.10 Either presentation is not uncommon in Sjögren’s patients but may be missed without a thorough slit lamp examination.
Figure 1: Ophthalmic branch of the trigeminal nerve leading to the corneal nerves.
Note
Neurotrophic keratitis is the medical term for inflammation of the cornea caused by decreased or absent corneal sensation, which can lead to damage in the epithelial tissue of the cornea and create open sores in the cornea called corneal ulcers.
Diagnostic Imaging and Corneal Nerve Pathologies Corneal nerve-related pathologies, crucial in understanding conditions like neurotrophic keratitis and neuropathic corneal pain, can be effectively identified and characterized using in vivo confocal microscopy imaging.11 This advanced imaging technique allows for detailed visualization of the subbasal nerve plexus in the cornea. In patients with neurotrophic keratitis, characterized by decreased corneal sensation, in vivo confocal microscopy reveals a reduced subbasal nerve density, reflecting nerve damage or loss.11 Conversely, in cases of neuropathic corneal pain, abnormal findings such as microneuromas (enlargements of the subbasal nerve endings at sites of nerve damage), abnormal nerve anastomoses (interconnections), truncated nerves, and infiltration of inflammatory cells around nerves can be observed.12,13 These conditions primarily manifest as sensory neuropathies affecting the corneal nerves, highlighting the utility of in vivo confocal microscopy not only in diagnosing but also in monitoring the progression and treatment response.
Note
In vivo confocal microscopy is a noninvasive imaging technique used for visualizing the microstructures of the eye at different levels of the tissue. The subbasal nerve plexus is a very dense bundle of nerves that run parallel to the corneal surface and is responsible for the distribution of nerves to the cornea. Since the subbasal nerve plexus is approximately 50 microns below the corneal surface, in vivo confocal microscopy can be used to better study these nerves.
Autonomic Nervous System Influence on Ocular Surface Health The autonomic nervous system plays a crucial role in maintaining the health of the ocular surface, primarily through its regulation of the lacrimal glands and the meibomian glands14. The parasympathetic and sympathetic branches of the autonomic nervous system innervate the lacrimal glands, controlling tear production and ensuring a stable tear film essential for ocular surface integrity and comfort. Parasympathetic stimulation promotes the secretion of aqueous tears, while the sympathetic nervous system modulates the lipid layer of the tear film by influencing meibomian gland activity. Disruptions in autonomic nervous system function, such as those seen in dysautonomia, may lead to imbalances in tear production and composition, contributing to dry eye symptoms and ocular surface disease. Understanding the role of autonomic nervous system in ocular surface health can help in the diagnosis and management of related conditions, including Sjögren’s disease, where autonomic dysfunction is a common manifestation.
Case Study and Observations In our ocular surface clinic at Johns Hopkins Wilmer Eye Institute, we routinely receive referrals for ocular surface assessment of patients suspected of having Sjögren’s. A 59-year-old female patient was referred for ocular surface assessment from the Johns Hopkins Postural Orthostatic Tachycardia Syndrome (POTS) Center. She reported dryness symptoms in her eyes, mouth, and skin, fatigue, dizziness, and generalized pain. She had a history of other autoimmune diseases such as Hashimoto’s thyroiditis and autoimmune autonomic gangliopathy. Her tilt table test was positive, leading to a POTS diagnosis. Serological workup revealed negative antibodies for anti-Sjögren's-related antigen A (SSA) and anti-Sjögren's-related antigen B (SSB), but antinuclear antibody (ANA) was positive at a titer of 1:640 with a dense fine speckled 70 (DFS70) pattern, which may indicate a non-autoimmune etiology15. However, her minor salivary gland biopsy focus score was 4.36, confirming Sjögren’s disease. During her ophthalmological assessment, she reported dryness, eye pain, and light sensitivity; however, her Schirmer test score was 16 mm in the right eye and 7 mm in the left eye. The ocular staining score (OSS) was 0 in both eyes according to the SICCA scoring system. Slit lamp examination revealed meibomian gland dysfunction but no other abnormalities to explain her ocular symptoms. Therefore, her ocular findings indicated neuropathic corneal pain. She was later started on intravenous immunoglobulin (IVIG) treatment, and at follow-up, she reported significant improvement in systemic and ocular symptoms within a few weeks of treatment. Noticing drastic improvement in her ocular symptoms following IVIG treatment led us to investigate ocular manifestations in patients with POTS with or without an associated autoimmune disease, such as Sjögren’s, to specifically explore the role of autonomic dysfunction in corneal sensory nerve health.
Note
You can read more about the diagnostic criteria of POTS, including tilt table test results in our Dysautonomia in Sjögren’s blog post.
Retrospective Study on POTS Patients A retrospective chart review was conductive including patients with POTS who underwent ocular surface assessment at the Johns Hopkins Wilmer Eye Institute between 2019-2024. Among 32 patients, 26 (81%) presented with dryness symptoms and/or eye pain, and 6 (19%) presented with visual symptoms only. The mean Schirmer score was 12.2 mm in the worse eye, and the mean OSS was 0.6; 23 patients graded 0. Among 26 patients reporting dry eye symptoms and/or eye pain, only 5 had OSS >1, leading to a diagnosis of neuropathic corneal pain in 21 patients. In-vivo confocal microscopy images of the subbasal nerve plexus layer in 6 patients showed varying abnormalities.
In this cohort, we identified 6 patients had Sjögren’s disease and 11 had other autoimmune diseases, such as undifferentiated connective tissue disease (UCTD), Hashimoto’s thyroiditis, and Raynaud's phenomenon. All 6 patients with Sjögren’s reported dryness and eye pain symptoms. Out of 6 with Sjögren’s, Schirmer test scores ranged between 4 and 35 mm, with a median value of 11 mm. OSS was 0 or 1 in all except for one with OSS 3.
This study, presented at the 25th International Ocular Surface Society Meeting in Seattle, WA in May 2024, suggested that patients with POTS may present with dryness symptoms and/or eye pain without significant ocular surface disease, indicating neuropathic corneal pain. Further research is warranted to elucidate the role of autonomic innervation in sensory nerve health, aiding in understanding the mechanisms of neuropathic corneal pain and guiding treatment modalities.
Conclusions and Future Directions The impact of Sjögren’s on the autonomic nervous system has gained more recognition in recent years. Autonomic neuropathy and painful sensory neuropathy are common autonomic nervous system presentations in patients with Sjögren’s disease.4 This preliminary study investigating ocular manifestations in patients with POTS provided insights into the ocular findings in a subgroup of Sjögren’s patients with dysautonomia. Given that nervous system manifestations of Sjögren’s may precede sicca manifestations, it is important to recognize ocular findings possibly associated with dysautonomia in Sjögren’s patients who do not present with hallmark sicca signs. This highlights the importance of slit lamp examinations for a complete ocular surface assessment, as dryness symptoms and eye pain may not always indicate sicca.
In summary, eye pain, burning, dryness sensation, and light sensitivity without ocular surface staining may suggest autonomic or painful sensory ocular neuropathy in patients with Sjögren’s. In vivo confocal microscopy may help diagnose nerve abnormalities and surrounding inflammatory cells. When referred for Sjögren’s assessment with ocular surface assessment, it is crucial to consider different presentations and provide appropriate feedback to the referring rheumatologists or neurologists. The systemic relevance of these ocular findings needs to be investigated along with the validation of objective methods such as in vivo confocal microscopy. This may help us understand the underlying pathogenesis in the development of neuropathy in these patients. Additionally, in vivo confocal microscopy could be used to non-invasively monitor sensory nerve health. Although the assessment of images captured using in vivo confocal microscopy still needs to be standardized, it has been widely utilized in the field of neuropathic corneal pain as an established method to assess corneal nerve health.16 A prospective study with a larger sample size is planned to validate these findings.
References
Sjogren H. On knowledge of keratoconjunctivitis sicca. keratitis filiformis due to lacrimal gland hypofunction. Acta Ophthalmol. 1933;11(1).
Smedby KE, Hjalgrim H, Askling J, et al. Autoimmune and Chronic Inflammatory Disorders and Risk of Non-Hodgkin Lymphoma by Subtype. JNCI J Natl Cancer Inst. 2006;98(1):51-60. doi:10.1093/jnci/djj004
Brito-Zerón P, Ramos-Casals M. Advances in the understanding and treatment of systemic complications in Sjögren’s syndrome. Curr Opin Rheumatol. 2014;26(5):520-527. doi:10.1097/BOR.0000000000000096
Chaaban N, Shaver T, Kshatriya S. Sjogren Syndrome-Associated Autonomic Neuropathy. Cureus. Published online June 1, 2022. doi:10.7759/cureus.25563
Tabbara K, Vera-Cristo C. Sjogren syndrome. Curr Opin Ophthalmol. 2000;11(6):449-454.
Shiboski CH, Shiboski SC, Seror R, et al. 2016 American College of Rheumatology/European League Against Rheumatism Classification Criteria for Primary Sjögren’s Syndrome: A Consensus and Data‐Driven Methodology Involving Three International Patient Cohorts. Arthritis Rheumatol. 2017;69(1):35-45. doi:10.1002/art.39859
Akpek EK, Mathews P, Hahn S, et al. Ocular and Systemic Morbidity in a Longitudinal Cohort of Sjögren’s Syndrome. Ophthalmology. 2015;122(1):56-61. doi:10.1016/j.ophtha.2014.07.026
Akpek EK, Bunya VY, Saldanha IJ. Sjögren’s Syndrome: More Than Just Dry Eye. Cornea. 2019;38(5):658-661. doi:10.1097/ICO.0000000000001865
Woodfield D, Tanner DL. Complicated Neurotrophic Corneal Ulcer in a Patient with Multiple Autoimmune Disorders. CRO Clin Refract Optom J. 2022;33(4). doi:10.57204/001c.57317
Goyal S, Hamrah P. Understanding Neuropathic Corneal Pain—Gaps and Current Therapeutic Approaches. Semin Ophthalmol. 2016;31(1-2):59-70. doi:10.3109/08820538.2015.1114853
Lambiase A, Sacchetti M. Diagnosis and management of neurotrophic keratitis. Clin Ophthalmol. Published online March 2014:571. doi:10.2147/OPTH.S45921
Asiedu K. Neurophysiology of corneal neuropathic pain and emerging pharmacotherapeutics. J Neurosci Res. 2024;102(1):e25285. doi:10.1002/jnr.25285
Chinnery HR, Rajan R, Jiao H, et al. Identification of presumed corneal neuromas and microneuromas using laser-scanning in vivo confocal microscopy: a systematic review. Br J Ophthalmol. 2022;106(6):765-771. doi:10.1136/bjophthalmol-2020-318156
Dartt DA. Neural regulation of lacrimal gland secretory processes: Relevance in dry eye diseases. Prog Retin Eye Res. 2009;28(3):155-177. doi:10.1016/j.preteyeres.2009.04.003
Aragón CC, González JD, Posso-Osorio I, et al. Anti-DFS70 antibodies: A new useful antibody in the exclusion of auto-immune diseases. Rev Colomb Reumatol Engl Ed. 2018;25(2):104-111. doi:10.1016/j.rcreue.2018.01.002
Shetty R, Dua HS, Tong L, et al. Role of in vivo confocal microscopy in dry eye disease and eye pain. Indian J Ophthalmol. 2023;71(4):1099-1104. doi:10.4103/IJO.IJO_3013_22
Sjögren's Dry Eye and Dysautonomia
One of the primary symptoms of Sjögren’s is dry eye. While there are many potential causes for Sjögren’s dry eye, such as inflammation in the lacrimal (tear-producing) glands that reduces tear production, dysautonomia may also play a role.
As part of Dry Eye Awareness month, we are sharing the expert article below entitled “Understanding the Ocular Health Implications of Dysautonomia in Sjögren’s Disease” written by Dr. Sezen Karakus and Jane Huang, BS.
Dysautonomia, which doctors may also call autonomic dysfunction, occurs when there is an underlying malfunction of the autonomic nervous system (ANS). This malfunction can cause impaired signaling of autonomic nerves and ganglia that relay messages from the brain to the internal organs and tissues.
According to experts, approximately 50% of patients with Sjögren’s experience some form of dysautonomia and the vast majority of patients are underdiagnosed with dysautonomia. In addition to the article below, you can read more about dysautonomia by visiting our Dysautonomia in Sjögren’s blog post.
We’d like to thank Dr. Karakus and Jane Huang, BS for writing this article on ocular health in Sjögren’s and dysautonomia and allowing us to share it with you during Dry Eye Awareness Month.
Understanding the Ocular Health Implications of Dysautonomia in Sjögren’s Disease
By Dr. Sezen Karakus (pictured) and Jane Huang, BS
Wilmer Eye Institute
John's Hopkins University
To assist with clarification on some of the medical terminology and techniques used, the Foundation also added some “Notes” within the article.
Introduction
Dry eye and dry mouth are hallmarks of Sjögren’s disease, originally described by Dr. Henrik Sjögren, an ophthalmologist who noticed a pattern in a group of patients with severe dry eye.1 These patients also experienced dry mouth, as well as generalized joint and muscle pain. The proposed pathogenesis was that inflammatory infiltration of the lacrimal and salivary glands would eventually destroy these glands, causing dry eye and dry mouth.1 Over the years, we have learned that Sjögren’s is a systemic disease that can affect multiple other organs and systems, including the central, peripheral, and autonomic nervous systems, with recent attention given to its impact on the autonomic nervous system.2–4 Dysautonomia is a condition where the autonomic nervous system does not function properly. Given the role of the autonomic nervous system in controlling various bodily functions, autonomic dysfunction may have a more significant impact on someone with Sjögren’s than we currently understand. Recognizing the possible role of dysautonomia in Sjögren’s can help us better understand some of the symptoms patients experience and consider different ways to address them. Here, we discuss the possible role of dysautonomia in ocular health in patients with Sjögren’s and how the presentation may differ from patients manifesting with classical keratoconjunctivitis sicca.
Note
Keratoconjunctivitis sicca is the medical term for dry eye caused by lack of tear production.
Classic Ocular Manifestations of Sjögren’s
Classic Sjögren’s ocular findings include reduced tear production, defined as aqueous tear deficiency, and ocular surface epitheliopathy, which is observed as ocular surface staining using vital dyes at the slit lamp.5 Tear production is typically measured by the Schirmer test, with a score of less than 5 mm in either eye adding 1 point toward Sjögren’s disease classification.6 Ocular surface staining is usually graded using the Sjögren’s International Clinical Collaborative Alliance Ocular Staining Score (SICCA OSS) system and is considered significant when the score exceeds 5 out of 12 in either eye.6 Dry eye symptoms often precede a Sjögren’s diagnosis by nearly a decade.7 Therefore, ophthalmologists play a crucial role in facilitating timely diagnosis by conducting a thorough ocular surface assessment.
Note
Ocular surface epitheliopathy is the medical term for damage to the epithelial tissue that covers the front of the cornea, which can lead to pain, redness, poor vision, and permanent damage to the cornea.
Dry Eye Symptoms and Diagnostic Challenges
Dry eye symptoms, however, do not always correlate well with clinical signs, making it essential to conduct a slit lamp examination for accurate diagnosis.8 Patients with severe ocular surface staining may have minimal discomfort, indicating reduced corneal sensation. Corneal nerves, which are small fiber sensory nerves stemming from the ophthalmic branch of the trigeminal nerve (see Figure 1 provided by the Foundation), can be damaged, leading to neurotrophic keratitis.9 If not addressed, epitheliopathy may progress to epithelial defects and corneal ulcers. Corneal sensation is a crucial part of the corneal reflex arc, also known as the blink reflex, which protects the eye from damage. Damage to the corneal nerves can impair this reflex, leading to further complications.
Conversely, some patients may experience severe symptoms disproportionate to their clinical signs. These patients may have no ocular surface staining but severe symptoms of dryness, burning, pain, and light sensitivity due to overly sensitive corneal nerves. This condition, known as “pain without stain,” indicates neuropathic corneal pain or corneal neuralgia.10 Either presentation is not uncommon in Sjögren’s patients but may be missed without a thorough slit lamp examination.
Figure 1: Ophthalmic branch of the trigeminal nerve leading to the corneal nerves.
Note
Neurotrophic keratitis is the medical term for inflammation of the cornea caused by decreased or absent corneal sensation, which can lead to damage in the epithelial tissue of the cornea and create open sores in the cornea called corneal ulcers.
Diagnostic Imaging and Corneal Nerve Pathologies
Corneal nerve-related pathologies, crucial in understanding conditions like neurotrophic keratitis and neuropathic corneal pain, can be effectively identified and characterized using in vivo confocal microscopy imaging.11 This advanced imaging technique allows for detailed visualization of the subbasal nerve plexus in the cornea. In patients with neurotrophic keratitis, characterized by decreased corneal sensation, in vivo confocal microscopy reveals a reduced subbasal nerve density, reflecting nerve damage or loss.11 Conversely, in cases of neuropathic corneal pain, abnormal findings such as microneuromas (enlargements of the subbasal nerve endings at sites of nerve damage), abnormal nerve anastomoses (interconnections), truncated nerves, and infiltration of inflammatory cells around nerves can be observed.12,13 These conditions primarily manifest as sensory neuropathies affecting the corneal nerves, highlighting the utility of in vivo confocal microscopy not only in diagnosing but also in monitoring the progression and treatment response.
Note
In vivo confocal microscopy is a noninvasive imaging technique used for visualizing the microstructures of the eye at different levels of the tissue. The subbasal nerve plexus is a very dense bundle of nerves that run parallel to the corneal surface and is responsible for the distribution of nerves to the cornea. Since the subbasal nerve plexus is approximately 50 microns below the corneal surface, in vivo confocal microscopy can be used to better study these nerves.
Autonomic Nervous System Influence on Ocular Surface Health
The autonomic nervous system plays a crucial role in maintaining the health of the ocular surface, primarily through its regulation of the lacrimal glands and the meibomian glands14. The parasympathetic and sympathetic branches of the autonomic nervous system innervate the lacrimal glands, controlling tear production and ensuring a stable tear film essential for ocular surface integrity and comfort. Parasympathetic stimulation promotes the secretion of aqueous tears, while the sympathetic nervous system modulates the lipid layer of the tear film by influencing meibomian gland activity. Disruptions in autonomic nervous system function, such as those seen in dysautonomia, may lead to imbalances in tear production and composition, contributing to dry eye symptoms and ocular surface disease. Understanding the role of autonomic nervous system in ocular surface health can help in the diagnosis and management of related conditions, including Sjögren’s disease, where autonomic dysfunction is a common manifestation.
Case Study and Observations
In our ocular surface clinic at Johns Hopkins Wilmer Eye Institute, we routinely receive referrals for ocular surface assessment of patients suspected of having Sjögren’s. A 59-year-old female patient was referred for ocular surface assessment from the Johns Hopkins Postural Orthostatic Tachycardia Syndrome (POTS) Center. She reported dryness symptoms in her eyes, mouth, and skin, fatigue, dizziness, and generalized pain. She had a history of other autoimmune diseases such as Hashimoto’s thyroiditis and autoimmune autonomic gangliopathy. Her tilt table test was positive, leading to a POTS diagnosis. Serological workup revealed negative antibodies for anti-Sjögren's-related antigen A (SSA) and anti-Sjögren's-related antigen B (SSB), but antinuclear antibody (ANA) was positive at a titer of 1:640 with a dense fine speckled 70 (DFS70) pattern, which may indicate a non-autoimmune etiology15. However, her minor salivary gland biopsy focus score was 4.36, confirming Sjögren’s disease. During her ophthalmological assessment, she reported dryness, eye pain, and light sensitivity; however, her Schirmer test score was 16 mm in the right eye and 7 mm in the left eye. The ocular staining score (OSS) was 0 in both eyes according to the SICCA scoring system. Slit lamp examination revealed meibomian gland dysfunction but no other abnormalities to explain her ocular symptoms. Therefore, her ocular findings indicated neuropathic corneal pain. She was later started on intravenous immunoglobulin (IVIG) treatment, and at follow-up, she reported significant improvement in systemic and ocular symptoms within a few weeks of treatment. Noticing drastic improvement in her ocular symptoms following IVIG treatment led us to investigate ocular manifestations in patients with POTS with or without an associated autoimmune disease, such as Sjögren’s, to specifically explore the role of autonomic dysfunction in corneal sensory nerve health.
Note
You can read more about the diagnostic criteria of POTS, including tilt table test results in our Dysautonomia in Sjögren’s blog post.
Retrospective Study on POTS Patients
A retrospective chart review was conductive including patients with POTS who underwent ocular surface assessment at the Johns Hopkins Wilmer Eye Institute between 2019-2024. Among 32 patients, 26 (81%) presented with dryness symptoms and/or eye pain, and 6 (19%) presented with visual symptoms only. The mean Schirmer score was 12.2 mm in the worse eye, and the mean OSS was 0.6; 23 patients graded 0. Among 26 patients reporting dry eye symptoms and/or eye pain, only 5 had OSS >1, leading to a diagnosis of neuropathic corneal pain in 21 patients. In-vivo confocal microscopy images of the subbasal nerve plexus layer in 6 patients showed varying abnormalities.
In this cohort, we identified 6 patients had Sjögren’s disease and 11 had other autoimmune diseases, such as undifferentiated connective tissue disease (UCTD), Hashimoto’s thyroiditis, and Raynaud's phenomenon. All 6 patients with Sjögren’s reported dryness and eye pain symptoms. Out of 6 with Sjögren’s, Schirmer test scores ranged between 4 and 35 mm, with a median value of 11 mm. OSS was 0 or 1 in all except for one with OSS 3.
This study, presented at the 25th International Ocular Surface Society Meeting in Seattle, WA in May 2024, suggested that patients with POTS may present with dryness symptoms and/or eye pain without significant ocular surface disease, indicating neuropathic corneal pain. Further research is warranted to elucidate the role of autonomic innervation in sensory nerve health, aiding in understanding the mechanisms of neuropathic corneal pain and guiding treatment modalities.
Conclusions and Future Directions
The impact of Sjögren’s on the autonomic nervous system has gained more recognition in recent years. Autonomic neuropathy and painful sensory neuropathy are common autonomic nervous system presentations in patients with Sjögren’s disease.4 This preliminary study investigating ocular manifestations in patients with POTS provided insights into the ocular findings in a subgroup of Sjögren’s patients with dysautonomia. Given that nervous system manifestations of Sjögren’s may precede sicca manifestations, it is important to recognize ocular findings possibly associated with dysautonomia in Sjögren’s patients who do not present with hallmark sicca signs. This highlights the importance of slit lamp examinations for a complete ocular surface assessment, as dryness symptoms and eye pain may not always indicate sicca.
In summary, eye pain, burning, dryness sensation, and light sensitivity without ocular surface staining may suggest autonomic or painful sensory ocular neuropathy in patients with Sjögren’s. In vivo confocal microscopy may help diagnose nerve abnormalities and surrounding inflammatory cells. When referred for Sjögren’s assessment with ocular surface assessment, it is crucial to consider different presentations and provide appropriate feedback to the referring rheumatologists or neurologists. The systemic relevance of these ocular findings needs to be investigated along with the validation of objective methods such as in vivo confocal microscopy. This may help us understand the underlying pathogenesis in the development of neuropathy in these patients. Additionally, in vivo confocal microscopy could be used to non-invasively monitor sensory nerve health. Although the assessment of images captured using in vivo confocal microscopy still needs to be standardized, it has been widely utilized in the field of neuropathic corneal pain as an established method to assess corneal nerve health.16 A prospective study with a larger sample size is planned to validate these findings.
References