Which Dry Eye? The Case for Precise Diagnostic Terminology in Ophthalmology.

Starting from an early age, we are taught to use our words wisely. As we mature, we observe how careless wording can have a negative impact on ourselves and others. However, in the field of ophthalmology, we use many terms that negatively impact our ability to communicate effectively with our colleagues as well as with our patients, leading to less than optimal care. It is time for some serious thought on the matter. The terms dry eye and dry eye disease are obvious examples of this problem. To a lay person, a physician who is not an ophthalmologist, or even an ophthalmologist who does not specialize in ocular surface disease, these terms imply that the eye is dry and does not have enough tears. However, a subgroup of ocular surface specialists have developed a much more sophisticated and inclusive definition for dry eye disease: “a multifactorial disease of the ocular surface characterized by a loss of homeostasis of the tear film, and accompanied by ocular symptoms, in which tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities play etiological roles.”1Craig J.P. Nelson J.D. Azar D.T. et al.TFOS DEWS II report executive summary.Ocul Surf. 2017; 15: 802-812Crossref PubMed Scopus (408) Google Scholar One problem with this definition is that it incorporates dozens of different conditions that have different pathologic causes and correspondingly different optimal therapies. So, when a colleague uses the term dry eye, how do we know if they are referring to this all-inclusive definition (akin to using the term uveitis instead of the specific type of uveitis) or to the specific problem of aqueous tear deficiency? Clearly, the pathogenesis of, and treatments for, Sjögren’s syndrome aqueous tear deficiency, diabetes-associated neurotrophic keratitis, ocular rosacea, and ocular surface neuropathic pain are different, yet they all fit into the definition of dry eye disease noted above, and as a result commonly are discussed as a single diagnostic entity: dry eye. This reality complicates communication with our patients and colleagues, makes it difficult to enroll homogenous study populations into clinical trials, and creates difficulties in comparing results across studies. Most importantly, it has treatment implications. Many clinical trials have focused on the treatment of ocular surface inflammation, despite suggestions that ocular surface inflammation may not contribute equally to all dry eye subtypes. Yet, even when attempting to split dry eye into subtypes, our words are misleading. The term evaporative dry eye, for example, is given in the scenario where tear production is adequate, but the tear film is unstable (typically assessed by measuring tear film breakup time). The evaporative rate of the aqueous layer is not measured, yet is incorporated in the naming of the disorder. Furthermore, this scenario (e.g., reduced tear breakup time with adequate tear production) can be seen in a number of other diseases (e.g., Salzmann nodular degeneration, epitheliopathy from topical medication toxicity) outside of primary tear deficiencies. One way to move forward is to re-examine our words and increase their specificity, choosing terminologies that more accurately reflect individual ocular surface disease phenotypes. Take, for example, dry eye symptoms, which often are used to diagnose dry eye disease, despite overwhelming data that symptoms and signs of dry eye correlate poorly. Studies have demonstrated that dry eye symptoms are correlated to a much greater degree with depression, anxiety, heightened dermal nociception, and nonocular pain syndromes (including migraine), than with signs of ocular surface disease. These associations suggest that some form of sensory nerve dysfunction, resulting in heightened awareness of the ocular surface, may play an important role in the symptoms of dry eye and that therapies to target nerve dysfunction may be a more appropriate approach to therapy. However, patients with ocular surface disease in the setting of Sjögren’s syndrome, rheumatoid arthritis, and graft-versus-host disease often report low dry eye symptoms score relative to clinical signs,2Vehof J. Sillevis Smitt-Kamminga N. Nibourg S.A. Hammond C.J. Predictors of discordance between symptoms and signs in dry eye disease.Ophthalmology. 2017; 124: 280-286Abstract Full Text Full Text PDF PubMed Scopus (90) Google Scholar suggesting just the opposite: that targeting ocular inflammation in these patients may be a more important therapeutic approach. These examples highlight the importance of splitting, rather than lumping, causes of dry eye. Improving specificity in our dry eye terminology would allow us to rethink the underlying contributors to an individual patient and to proceed with treatment in a more rational manner. Linguists have taught us that word choice profoundly influences how we think about things. For this very reason, even experienced ophthalmologists immediately may become anchored to thinking about a dry ocular surface when the terms dry eye or dry eye disease are used.Improving specificity in our dry eye terminology would allow us to rethink the underlying contributors to an individual patient and to proceed with treatment in a more rational manner. Improving specificity in our dry eye terminology would allow us to rethink the underlying contributors to an individual patient and to proceed with treatment in a more rational manner. Many other examples exist in which our word choice negatively impacts communication with and optimal care of patients in our ophthalmology practice. For example, the terms pterygium and recurrent pterygium both are used commonly to describe a fibrovascular, wing-like growth of conjunctivae over the cornea, typically in a nasal or temporal limbal location. However, the pathophysiologic features of these two conditions are thought to be very different. A primary pterygium is thought to be the result of ultraviolet light-induced DNA damage causing an epithelial to mesenchymal transformation of conjunctival tissue and the resultant migration of this tissue onto the cornea over many years. In contrast, recurrent pterygium occurs rapidly and most often represents aberrant wound healing after surgery, both as a result of patient-related factors and surgical technique.3Singh G. Pterygium and its surgery.in: Smolin G. Thoft R. The Cornea: Scientific Foundations and Clinical Practice. 3rd ed. Little, Brown, Boston1994Google Scholar If we think about primary and recurrent pterygia as separate entities, then it becomes clear we have only 1 chance during surgery to resolve the primary process. As soon as the pterygium recurs, it is a secondary process with a different pathophysiologic basis: an exuberant fibrovascular growth that is more aggressive and less easy to address surgically. But the words we use to describe these two very different processes lead us to think otherwise and influence our therapeutic decision-making. In some instances, imprecise and misleading word choice in ophthalmology has been recognized as a problem, and terms have been renamed. Schnyder’s crystalline corneal dystrophy was renamed Schnyder’s corneal dystrophy because it was recognized that about half the cases did not have crystals in the corneal stroma observable by slit-lamp examination.4Weiss J.S. Moller H.U. Lisch W. et al.The IC3D classification of the corneal dystrophies.Cornea. 2008; 27: S1-S83Crossref PubMed Scopus (277) Google Scholar The term choroidal neovascularization suggests that neovascular lesions in age-related macular degeneration arise from the choroid. With improved imaging techniques, we have learned that retinal angiomatous proliferation lesions, which comprise about one-third of all wet age-related macular degeneration lesions, arise from the retinal circulation, prompting a change in nomenclature from choroidal neovascularization to macular neovascularization, with different subtypes depending on the origin of the neovascularization.5Spaide R.F. Jaffe G.J. Sarraf D. et al.Consensus nomenclature for reporting neovascular age-related macular degeneration data: Consensus on Neovascular Age-Related Macular Degeneration Nomenclature Study Group.Ophthalmology. 2020; 127: 616-636Abstract Full Text Full Text PDF PubMed Scopus (301) Google Scholar Central serous retinopathy suggests that the subretinal fluid that accumulates in this condition arises from a retinal abnormality, but enhanced depth imaging OCT and digital indocyanine green angiography have demonstrated that the choroid is thickened and hyperpermeable in eyes with central serous retinopathy. Thus, the term central serous chorioretinopathy is more appropriate because the pathogenesis of central serous chorioretinopathy seems to be the result of choroidal abnormalities that secondarily affect the retinal pigment epithelium and neurosensory retina. Furthermore, because scleral thickness is significantly greater in eyes with central serous chorioretinopathy,6Imanaga N. Terao N. Nakamine S. et al.Scleral thickness in central serous chorioretinopathy.Ophthalmol Retina. 2021; 5: 285-291Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar we soon may find ourselves using the term central serous chorioscleropathy to describe this condition accurately. The uveitis community came together after recognizing the problem with terminology in their field and developed the Standardization of Uveitis Nomenclature criteria to improve reporting of clinical data and to facilitate communication among physicians.7Jabs D.A. Nussenblatt R.B. Rosenbaum J.T. Standardization of Uveitis Nomenclature Working Group. Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop.Am J Ophthalmol. 2005; 140: 509-516Abstract Full Text Full Text PDF PubMed Scopus (3145) Google Scholar Although new terminology may seem difficult to adopt for clinicians out of training, it is important because the words we use influence how we think about disease pathogenesis and treatment. However, it is not only the naming of a disease that is important to consider. We also need to be careful about how we describe the course of disease. For example, the word resistant is often used to describe an infectious process that is not responding clinically to treatment. The use of this word often leads the clinician to consider drug resistance as the cause of a poor clinical response, but many factors can contribute to clinical resistance. In herpes simplex epithelial keratitis, often these other factors, such as a poor immune response (e.g., atopic or iatrogenic), neurotrophic keratopathy, stromal inflammation, poor patient compliance, or drug toxicity, are responsible for slower than expected resolution of the clinical disease. Unfortunately, as soon as the term resistant enters the chart or clinical discussion, the focus becomes on antiviral drug resistance, rather than on clinical resistance caused by one of many possible factors. These are but a few examples of words in ophthalmology that can have a negative impact on patient care. This editorial is meant to remind us that words really do matter, in life and in ophthalmology. As such, we need to choose our words wisely and to improve specificity in our terminology. We believe we should start with one of the most nonspecific terms in ophthalmology: dry eye. It is time to consider a standardized nomenclature (e.g., a nomenclature of diseases of the ocular surface) to improve discussion about the many different conditions that fall under the term dry eye. Until then, we encourage physicians to use their words wisely and to use accurate words to identify potential contributors to ocular surface symptoms that can include local (e.g., aqueous tear deficiency, medication toxicity), periocular (e.g., rosacea, lagophthalmos), and systemic (e.g., autoimmune disease, hormone imbalance) processes that can be addressed as part of an individualized treatment plan. CorrigendumOphthalmologyVol. 130Issue 6PreviewThe authors of “Which Dry Eye? The Case for Precise Diagnostic Terminology in Ophthalmology” (Ophthalmology 2023; 130: 239-41) would like to make the following correction to Dr. Todd Margolis’s affiliation (in bold): Full-Text PDF