Dry eye disease (DED) is a broad term that includes a diverse group of clinical disorders. Aqueous-deficient dry eye (ADDE), a subtype of DED, is characterized by decreased tear production by the lacrimal gland. It can be seen in up to one-third of individuals with DED and can be comorbid with a systemic autoimmune process or occur secondary to an environmental insult. Since ADDE can be a source of long-term suffering and severe visual impairment, early identification and adequate treatment are imperative. Multiple etiologies can underlie ADDE, and it is critical to identify the underlying cause to not only improve the ocular health but also to improve the overall quality of life and well-being of affected individuals. This review discusses the various etiologies of ADDE, highlights a pathophysiology-based approach for evaluating underlying contributors, outlines various diagnostic tests, and reviews treatment options. We present the current standards and discuss ongoing research in this field. Through this review, we propose a treatment algorithm that would be useful for an ophthalmologist in diagnosing and managing individuals with ADDE.

A decrease of the Tear Meniscus Height (TMH) has been proposed as a useful indicator for Aqueous Deficient Dry Eye (ADDE) categorization. The present study aimed to calculate a TMH cut-off criterion for the categorization or severity assessment of ADDE with the Tearscope. 200 participants with a previous Dry Eye Disease (DED) diagnosis according to TFOS DEWS-II criteria were recruited. TMH by slit-lamp illumination and Lipid Layer Pattern (LLP) with Tearscope were assessed to categorise the participants into the ADDE or the Evaporative Dry Eye (EDE) group. The ADDE group was also subdivided into Mild-moderate ADDE and Moderate-severe ADDE based on TMH with slit-lamp. Additionally, the TMH was measured by Tearscope (TMH-Tc). Receiver Operating Characteristics showed that the TMH-Tc have a diagnostic capability to differentiate between ADDE and EDE participants, and between Mild-moderate or Moderate-severe ADDE, with a cut-off value of 0.159 mm (AUC = 0.843 ± 0.035, p < 0.001; sensitivity: 86.4%; specificity: 75.4%) and 0.105 mm (AUC = 0.953 ± 0.025, p < 0.001; sensitivity: 98.1%; specificity: 80.0%), respectively. The present study proposed a cut-off criterion to differentiate between ADDE and EDE participants, or between ADDE severities through TMH assessed by Tearscope.

This article provides a comprehensive view of the issue of dry eye. It emphasizes provisions of the Tear Film and Ocular Surface Society, discusses the new classification and definition of dry eye based on its pathophysiology, and emphasizes the correct diagnostic and therapeutic approaches, which appears in the form of algorithms. Dry eye is 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. Dry eye disease is a dynamic and complex disease of the ocular surface and ocular adnexa with known risk factors. It is a disease with a cyclical character, in which the most important step is to find the etiological trigger, to restore homeostasis and break the vicious circle. The key elements in the diagnosis are increased osmolarity of the tear film and inflammation of the ocular surface, which are accompanied by ocular symptoms (discomfort, visual disturbance). Inflammation is not always associated with hyperemia and can be confirmed by several techniques and methods. However, in current clinical practice, there is still no \"gold standard\" and sufficient tests to diagnose inflammation of the ocular surface. The treatment of dry eye disease must be individualized, dynamic and optimized for each stage of the disease.

This article provides a comprehensive view of the issue of dry eye. It emphasizes provisions of the Tear Film and Ocular Surface Society, discusses the new classification and definition of dry eye based on its pathophysiology, and emphasizes the correct diagnostic and therapeutic approaches, which appears in the form of algorithms. Dry eye is 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. Dry eye disease is a dynamic and complex disease of the ocular surface and ocular adnexa with known risk factors. It is a disease with a cyclical character, in which the most important step is to find the etiological trigger, to restore homeostasis and break the vicious circle. The key elements in the diagnosis are increased osmolarity of the tear film and inflammation of the ocular surface, which are accompanied by ocular symptoms (discomfort, visual disturbance). Inflammation is not always associated with hyperemia and can be confirmed by several techniques and methods. However, in current clinical practice, there is still no \"gold standard\" and sufficient tests to diagnose inflammation of the ocular surface. The treatment of dry eye disease must be individualized, dynamic and optimized for each stage of the disease.

This article provides a comprehensive view of the issue of dry eye. It emphasizes provisions of the Tear Film and Ocular Surface Society, discusses the new classification and definition of dry eye based on its pathophysiology, and emphasizes the correct diagnostic and therapeutic approaches, which appears in the form of algorithms. Dry eye is 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. Dry eye disease is a dynamic and complex disease of the ocular surface and ocular adnexa with known risk factors. It is a disease with a cyclical character, in which the most important step is to find the etiological trigger, to restore homeostasis and break the vicious circle. The key elements in the diagnosis are increased osmolarity of the tear film and inflammation of the ocular surface, which are accompanied by ocular symptoms (discomfort, visual disturbance). Inflammation is not always associated with hyperemia and can be confirmed by several techniques and methods. However, in current clinical practice, there is still no \"gold standard\" and sufficient tests to diagnose inflammation of the ocular surface. The treatment of dry eye disease must be individualized, dynamic and optimized for each stage of the disease.

This article provides a comprehensive view of the issue of dry eye. It emphasizes provisions of the Tear Film and Ocular Surface Society, discusses the new classification and definition of dry eye based on its pathophysiology, and emphasizes the correct diagnostic and therapeutic approaches, which appears in the form of algorithms. Dry eye is 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. Dry eye disease is a dynamic and complex disease of the ocular surface and ocular adnexa with known risk factors. It is a disease with a cyclical character, in which the most important step is to find the etiological trigger, to restore homeostasis and break the vicious circle. The key elements in the diagnosis are increased osmolarity of the tear film and inflammation of the ocular surface, which are accompanied by ocular symptoms (discomfort, visual disturbance). Inflammation is not always associated with hyperemia and can be confirmed by several techniques and methods. However, in current clinical practice, there is still no \"gold standard\" and sufficient tests to diagnose inflammation of the ocular surface. The treatment of dry eye disease must be individualized, dynamic and optimized for each stage of the disease.

An altered ocular surface microbiota may contribute to the pathophysiology of dry eye disease. The aim of the study was to explore potential differences in microbiota diversity and composition in aqueous tear-deficient dry eye (with and without ocular graft-versus-host disease) compared with controls.
Swab samples from the inferior fornix of the conjunctiva were obtained from patients with aqueous tear-deficient dry eye with and without ocular graft-versus-host disease (n = 18, n = 21, respectively) and controls (n = 28). Isolated bacterial DNA from swabs were analyzed with 16S rRNA gene amplicon sequencing.
Decreased microbiota diversity was observed in patients with aqueous tear-deficient dry eye (p ≤ 0.003) who also showed a difference in microbiota composition compared with controls (p = 0.001). Although several genera were less abundant in aqueous tear-deficient dry eye, a minimal core ocular surface microbiota comprising five genera was shared by >75% of the study participants: Enhydrobacter, Brevibacterium, Staphylococcus, Streptococcus and Cutibacterium. Pseudomonas was identified as a bacterial biomarker for controls and Bacilli for patients with aqueous tear-deficient dry eye.
Ocular surface microbiota in patients with aqueous tear-deficient dry eye was characterized by an aberrant microbiota composition in comparison to controls, with decreased diversity and reduced relative abundances of several genera. Additionally, a few genera were present in most of the study population, indicating that a minimal core ocular surface microbiota may exist.

Dry eye disease (DED) is categorised by pathophysiology as aqueous deficient dry eye (ADDE), evaporative dry eye (EDE) or mixed. Treatment should be tailored to DED pathophysiology, but this is challenging to determine. This Delphi consultation aimed to categorise and weight signs and symptoms to help identify the evaporative or aqueous deficient DED origin.
A panel of French DED experts created an initial list of 77 DED signs and symptoms. In a Delphi consultation, experts categorised items by DED pathophysiology. Likert scoring was used to indicate whether items were strongly or moderately indicative of ADDE or EDE. Items could also be judged non-applicable to DED, with the opportunity to suggest alternative diagnoses.
Experts attributed 19 items (of which 11 were strongly indicative) to a pathophysiology of EDE and 12 items (of which four were strongly indicative) to ADDE. Items scored strongly indicative with agreement >90% for EDE were previous chalazia, rosacea/rhinophyma, telangiectasias of eyelid margin and thick non-expressible meibomian gland secretions, and for ADDE were Sjögren syndrome or associated disease, and Schirmer <5 mm after 5 min (without anaesthesia). Seventeen items indicated neither pathophysiology and 18 items were found to be suggestive of alternative diagnoses.
This Delphi consultation categorised signs and symptoms, using an innovative weighting system to identify DED pathophysiology. An algorithm integrating the weighting of each sign and symptom of an individual patient would be valuable to help general ophthalmologists to classify the DED subtype and tailor treatment to DED underlying mechanism.