Postural orthostatic tachycardia syndrome (POTS) is a disorder of the autonomic nervous system. This part of the nervous system manages functions that occur automatically, such as regulation of heart rate, blood pressure, sweating and body temperature. POTS symptoms may include lightheadedness, difficulty thinking and concentrating, fatigue and blurry vision, as well as a significant rise in heart rate when standing.

Johns Hopkins Medicine is home to one of the few POTS programs in the nation. The Johns Hopkins center treats adults and children.

Sezen Karakus, M.D., an assistant professor of ophthalmology at the Wilmer Eye Institute, Johns Hopkins Medicine, specializes in corneal and external eye diseases. She took an interest in POTS in recent years, and joined the Johns Hopkins Medicine POTS program to provide an ophthalmologic perspective on the disease.

Karakus’s interest in POTS began after a health care practitioner diagnosed a longtime Karakus patient with POTS and sent the patient to her for a Sjögren’s disease assessment. Karakus had seen the patient annually for eye exams — the patient complained of nonspecific eye pain and light sensitivity, but her exam results were always normal. Sjögren’s is commonly known to cause dry eye and dry mouth, but this patient did not have dry eye. Her antibody test for Sjögren’s was negative, but a lip biopsy, which is a more definitive test often conducted after a negative antibody test result, confirmed the presence of the disease. Karakus then gave her an assessment for Sjögren’s by performing a Schirmer test to measure tear production and an ocular surface staining test to grade surface dryness. The Schirmer test indicated slightly reduced tear production, but still within the normal range, while the surface staining did not indicate typical Sjögren’s.

These results led Karakus to suspect that the patient’s eye pain and light sensitivity were due to a neurologic issue. Sure enough, the patient’s eye symptoms improved after starting intravenous immunoglobulin therapy, which is used to treat POTS and Sjögren’s disease. “When her eye symptoms improved along with other POTS-related symptoms, I knew there must have been some kind of connection with that,” Karakus says.

Karakus’s clinical and research interests include corneal neuropathic pain (corneal neuralgia). This is when people have dry eye symptoms but no clinical dry eye signs. “Their corneal nerves don’t function properly, and they’re giving the wrong signals,” Karakus says. “The nerves are agitated but they don’t have anything visible at the exam to cause that agitation.”

However, if in vivo confocal microscopy can be used to image corneal nerves, abnormal nerves and surrounding inflammatory cells can be captured to explain the symptoms. “We can't truly understand what is wrong until we have the right tools to reveal the hidden problems,” Karakus says.

Once Karakus made the connection between the patient’s symptoms and POTS, she began imaging patients with POTS by using in vivo confocal microscopy, and she observed that corneal nerves of most patients with POTS or without Sjögren’s were not normal. This explained their symptoms. She also noted that most patients with POTS complain of dryness, eye pain and light sensitivity, despite not having clinical signs of dry eye.

As a result of this patient experience, Karakus wanted to partner with the POTS program. Patients who have POTS and eye symptoms are referred to Karakus for a comprehensive exam including in vivo confocal microscopy, pain and corneal sensitivity assessments and a complete ocular surface exam.

Karakus has devoted one day each month to seeing patients with POTS. The program’s founder and director, Tae Chung, an associate professor of physical medicine and rehabilitation as well as neurology at Johns Hopkins, says Karakus is the first ophthalmologist to join the POTS team since its inception in 2017.

Chung says Karakus has been a natural fit with the team, and patients with POTS appreciate her efforts. “She understands what they're going through and this delicate problem that they have,” Chung says. “A lot of my patients are really loving that there’s an ophthalmologist who is dedicated to their POTS-related eye issues.”

Chung says Karakus is an invaluable member of the POTS team. As understanding of the cause of the disorder develops, he sees potential for research collaboration. “The eye can be a window to this autonomous dysfunction,” he says. “There’s great potential with this collaboration to identify this autoimmune subset of POTS.”

POTS research at work

As Karakus continues to help patients with POTS from the ophthalmologic perspective, she wants to build more awareness about POTS and its connections to the eye, specifically the cornea. In a Sjögren’s Quarterly cover story published earlier this year, Karakus addresses in detail a study she conducted in which she found that most patients with both Sjögren’s disease and POTS — thus autonomic dysfunction — experience eye symptoms due to corneal nerve damage without having typical Sjögren’s-type dry eye. Through her research, she seeks to unravel the potential connection between autonomic dysfunction and corneal nerve health.

Karakus points out that eye pain, burning and light sensitivity might be signs of corneal neuropathic pain. She emphasizes the importance of performing a complete ocular surface exam using a slit lamp to differentiate corneal neuropathic pain from dry eye, which can be an early manifestation in patients who may not yet have classic Sjögren’s dry eye.

Karakus also highlights how in vivo confocal microscopy could help detect nerve damage, especially in patients with both Sjögren’s and POTS. She believes more research is needed to confirm these findings and to improve how nerve issues are diagnosed in people with these conditions.