NIH specialist: Multifactorial nature of dry eye is most challenging

Janine Clayton, MD
Janine Austin Clayton

Ophthalmologist Janine Austin Clayton, MD, spoke with Primary Care Optometry News about the review article she developed to assist clinicians in diagnosing and treating dry eye disease.

At the NIH, Clayton is associate director for research on women’s health and director of the NIH Office of Research on Women’s Health.

Her article provides an overview on the subtypes of the disease to better enable clinicians in diagnosis and treatment for this painful condition that affects nearly 5 million Americans.

PCON: What do you think are the most misunderstood aspects of dry eye from a patient and/or a physician perspective?

Clayton: The most misunderstood aspect of dry eye disease for patients is the multifactorial nature of the disease, which encompasses a host of signs and symptoms, has many possible causes and cannot be diagnosed with any one test. Signs and symptoms of the disease vary greatly both within and among individuals. There is no single definitive dry eye treatment that works for everyone, and outcomes of individual treatments are highly variable as well. These complexities can leave patients frustrated as they undergo different diagnostic tests and try different options to get relief from this painful condition. Many health care practitioners without specialty knowledge of the disease may have an incomplete understanding of the complex nuances of dry eye disease or the pain that can be caused by the disease. In fact, some practitioners are also unaware of the degrading effect that dry eye can have on visual function.

Two main goals of my review were to discuss the importance of understanding these nuances and to emphasize how optimal treatment depends on identifying a patient’s most likely form and subtype of dry eye, while recognizing the influence of environmental factors and the potential overlap between forms and/or subtypes (Clayton).

PCON: How can optometrists do a better job at diagnosing and managing dry eye patients?

Clayton: It is important for optometrists to be aware of the multiple pathogenic pathways to dry eye disease and to take a methodical approach to diagnosing and treating patients, such as following the TFOS DEWS II staged management algorithm (Jones et al.). Employing validated questionnaires, like the Ocular Surface Disease Index or Standardized Patient Evaluation of Eye Dryness questionnaire, is one good way to follow a patient’s symptoms and response to treatment. It is also helpful to consider the range of risk factors for dry eye, such as recurrent blepharitis, refractive eye surgery, autoimmune disease, female sex and age. Knowledge of the many possible etiologies of this heterogeneous disease is the key to effectively managing dry eye patients, because optimal intervention strategies vary depending on the form and subtype of the disease.

PCON: Do you think that eye rubbing plays a role in inflammation and dry eye?

Clayton: One of the core mechanisms underlying dry eye disease in many patients is a vicious cycle of inflammation, in which inflammation is both a cause and effect of disrupted tear film homeostasis. Indeed, eye rubbing may exacerbate ocular surface inflammation. We may have the urge to rub our eyes from time to time due to fatigue, exposure to irritants or allergies. However, rubbing the eyes can introduce infectious agents into the eyes and may even result in corneal damage by a variety of mechanisms. Dry eye patients, in particular, should be cautioned against rubbing their eyes due to their compromised tear-film homeostasis and the possibility of preexisting corneal damage.

PCON: Do you have any thoughts about using a neurostimulation mechanism (like TrueTear, Allergan) to treat dry eye?

Clayton: The neurostimulation approach to increasing tear production offers potential promise as a new treatment option for dry eye patients, though we will have a much clearer picture of long-term patient outcomes as post-marketing data become available. A big advantage of the neurostimulation approach is that natural tear production is stimulated, as opposed to artificial lubrication of the eyes. It is important to bear in mind, however, that no single treatment option is likely to provide a one-size-fits-all approach to managing this multifactorial disease.

PCON: Should optometrists be doing more to encourage proper lid hygiene?

Clayton: Anyone performing slit lamp examinations of patients’ eyes has the opportunity to detect signs of lid disease and to counsel people on lid hygiene when they see signs of concern. Given how frequently dry eye is associated with lid margin disease, optometrists should routinely examine the lid margins and encourage proper lid hygiene in all their patients. Nowadays, practitioners have access to several options for improving lid hygiene, such as warm compresses, lid wipes, tea tree oil and short-term topical antibiotics.

PCON: Where should researchers focus their efforts within dry eye research to better understand the condition and lead to better, longer-term treatments?

Clayton: While there is no single area in which most research should be focused for this multifactorial disease, there is a great need for more research on certain topics. For example, a better understanding of pain mechanisms associated with dry eye disease and the neural regulation of tear production would greatly advance our understanding of the disease and may contribute to the development of better treatments as well. Right now, I see a lot of exciting preclinical research in the works on both the evaporative and aqueous-deficient sides of dry eye disease, which is great. A multipronged approach is definitely needed for dry eye disease.

Regardless of what organ system or biomedical research discipline one is working in, it is always important to consider sex as a biological variable and report data disaggregated by sex in all realms and phases of biomedical research. Doing so is essential to enhancing the rigor and reproducibility of science, because sex and gender influences on health and disease are so common across disciplines.

For example, sex and gender have prominent influences on dry eye disease. We know that the prevalence of dry eye disease is notably higher in women than men, and we know that sex hormones have important influences on many of the pathways and mechanisms underlying this heterogeneous disease. As a result, all dry eye researchers should design their studies bearing in mind the possibility or even likelihood of encountering meaningful pathophysiological sex influences. Doing so will make for better science, and it will hasten the development of new and better dry eye treatments for women as well as men.

References:

Clayton JA. New Engl J Med. 2018;doi:10.1056/NEJMra1407936.

Jones L, et al. Ocul Surf. 2017;doi:10.1016/j.jtos.2017.05.006.

Disclosure: Clayton reported no relevant financial disclosures.

Janine Clayton, MD
Janine Austin Clayton

Ophthalmologist Janine Austin Clayton, MD, spoke with Primary Care Optometry News about the review article she developed to assist clinicians in diagnosing and treating dry eye disease.

At the NIH, Clayton is associate director for research on women’s health and director of the NIH Office of Research on Women’s Health.

Her article provides an overview on the subtypes of the disease to better enable clinicians in diagnosis and treatment for this painful condition that affects nearly 5 million Americans.

PCON: What do you think are the most misunderstood aspects of dry eye from a patient and/or a physician perspective?

Clayton: The most misunderstood aspect of dry eye disease for patients is the multifactorial nature of the disease, which encompasses a host of signs and symptoms, has many possible causes and cannot be diagnosed with any one test. Signs and symptoms of the disease vary greatly both within and among individuals. There is no single definitive dry eye treatment that works for everyone, and outcomes of individual treatments are highly variable as well. These complexities can leave patients frustrated as they undergo different diagnostic tests and try different options to get relief from this painful condition. Many health care practitioners without specialty knowledge of the disease may have an incomplete understanding of the complex nuances of dry eye disease or the pain that can be caused by the disease. In fact, some practitioners are also unaware of the degrading effect that dry eye can have on visual function.

Two main goals of my review were to discuss the importance of understanding these nuances and to emphasize how optimal treatment depends on identifying a patient’s most likely form and subtype of dry eye, while recognizing the influence of environmental factors and the potential overlap between forms and/or subtypes (Clayton).

PCON: How can optometrists do a better job at diagnosing and managing dry eye patients?

Clayton: It is important for optometrists to be aware of the multiple pathogenic pathways to dry eye disease and to take a methodical approach to diagnosing and treating patients, such as following the TFOS DEWS II staged management algorithm (Jones et al.). Employing validated questionnaires, like the Ocular Surface Disease Index or Standardized Patient Evaluation of Eye Dryness questionnaire, is one good way to follow a patient’s symptoms and response to treatment. It is also helpful to consider the range of risk factors for dry eye, such as recurrent blepharitis, refractive eye surgery, autoimmune disease, female sex and age. Knowledge of the many possible etiologies of this heterogeneous disease is the key to effectively managing dry eye patients, because optimal intervention strategies vary depending on the form and subtype of the disease.

PCON: Do you think that eye rubbing plays a role in inflammation and dry eye?

Clayton: One of the core mechanisms underlying dry eye disease in many patients is a vicious cycle of inflammation, in which inflammation is both a cause and effect of disrupted tear film homeostasis. Indeed, eye rubbing may exacerbate ocular surface inflammation. We may have the urge to rub our eyes from time to time due to fatigue, exposure to irritants or allergies. However, rubbing the eyes can introduce infectious agents into the eyes and may even result in corneal damage by a variety of mechanisms. Dry eye patients, in particular, should be cautioned against rubbing their eyes due to their compromised tear-film homeostasis and the possibility of preexisting corneal damage.

PCON: Do you have any thoughts about using a neurostimulation mechanism (like TrueTear, Allergan) to treat dry eye?

Clayton: The neurostimulation approach to increasing tear production offers potential promise as a new treatment option for dry eye patients, though we will have a much clearer picture of long-term patient outcomes as post-marketing data become available. A big advantage of the neurostimulation approach is that natural tear production is stimulated, as opposed to artificial lubrication of the eyes. It is important to bear in mind, however, that no single treatment option is likely to provide a one-size-fits-all approach to managing this multifactorial disease.

PCON: Should optometrists be doing more to encourage proper lid hygiene?

Clayton: Anyone performing slit lamp examinations of patients’ eyes has the opportunity to detect signs of lid disease and to counsel people on lid hygiene when they see signs of concern. Given how frequently dry eye is associated with lid margin disease, optometrists should routinely examine the lid margins and encourage proper lid hygiene in all their patients. Nowadays, practitioners have access to several options for improving lid hygiene, such as warm compresses, lid wipes, tea tree oil and short-term topical antibiotics.

PCON: Where should researchers focus their efforts within dry eye research to better understand the condition and lead to better, longer-term treatments?

Clayton: While there is no single area in which most research should be focused for this multifactorial disease, there is a great need for more research on certain topics. For example, a better understanding of pain mechanisms associated with dry eye disease and the neural regulation of tear production would greatly advance our understanding of the disease and may contribute to the development of better treatments as well. Right now, I see a lot of exciting preclinical research in the works on both the evaporative and aqueous-deficient sides of dry eye disease, which is great. A multipronged approach is definitely needed for dry eye disease.

Regardless of what organ system or biomedical research discipline one is working in, it is always important to consider sex as a biological variable and report data disaggregated by sex in all realms and phases of biomedical research. Doing so is essential to enhancing the rigor and reproducibility of science, because sex and gender influences on health and disease are so common across disciplines.

For example, sex and gender have prominent influences on dry eye disease. We know that the prevalence of dry eye disease is notably higher in women than men, and we know that sex hormones have important influences on many of the pathways and mechanisms underlying this heterogeneous disease. As a result, all dry eye researchers should design their studies bearing in mind the possibility or even likelihood of encountering meaningful pathophysiological sex influences. Doing so will make for better science, and it will hasten the development of new and better dry eye treatments for women as well as men.

References:

Clayton JA. New Engl J Med. 2018;doi:10.1056/NEJMra1407936.

Jones L, et al. Ocul Surf. 2017;doi:10.1016/j.jtos.2017.05.006.

Disclosure: Clayton reported no relevant financial disclosures.