Application frequency - key indicator for the efficiency of severe dry eye disease treatment - evidence for the importance of molecular weight of hyaluronan in lubricating agents.

PURPOSE: Lubricant eye drops are the main therapeutic resource for dry eye disease (DED), with each drop representing the equivalent of ocular surface disease treatment. Thus, any reduction in the frequency of eye drop application reflects a degree of therapeutic success. Considering also the socioeconomic burden of DED, we investigated eye drop application frequency (DF) as a parameter to potentially track the success of therapy in severe DED. Hyaluronan (HA)-containing eye drops have become the first choice for tear substitution in many countries, and recent data indicate that the average molecular weight (Mw) of HA determines the therapeutic efficacy of such eye drops. This post-hoc subgroup analysis of a previously published multicentre prospective randomized open-label study, HYLAN M, is set out to compare the effects of very high Mw HA (hylan A) eye drops to comparator eye drops, containing lower Mw HA (control). METHODS: Patients with severe DED (n = 47), recruited as part of the larger HYLAN M prospective, multicentre, open-label study, were randomized into two groups: hylan A and control group. In the hylan A group, 24 patients replaced their HA-containing eye drops with eye drops containing 0.15% hylan A, whereas the 23 control patients continued to use comparator HA eye drops. The DF was recorded daily by all participants over 8 weeks, and other subjective and objective parameters of DED were assessed at the time of inclusion (baseline), as well as at week 4 and 8. RESULTS: There was a significant decrease in DF in the hylan A users between the baseline and week 4 (p = 0.004), remaining stable until week 8. Indeed, in contrast to the baseline, the hylan A group had a significantly lower DF than the control group at weeks 4 (p = 0.018) and 8 (p = 0.008). Likewise, the ocular surface disease index (OSDI) improved significantly between the time of inclusion and week 4 (p < 0.001) in hylan A users, remaining stable until week 8. The OSDI was similar in both groups at the baseline but it was significantly lower in the hylan A group than in the control group at week 4 (p = 0.002), remaining lower at week 8. Such a decrease in the DF and OSDI was not witnessed in the control group at any time point. The objective parameters assessed did not differ significantly within or between the two groups. CONCLUSION: When treating severe DED, the DF can be significantly reduced by using very high Mw HA (3 MDa) lubricant eye drops, which better alleviate DED symptoms and decrease the OSDI scores. These drops not only provide an attractive and comfortable alternative for patients with severe DED but also offer the possibility of reducing the disease's socioeconomic burden, both for affected individuals and society as a whole.

Ocular Surface Allostasis-When Homeostasis Is Lost: Challenging Coping Potential, Stress Tolerance, and Resilience.

The loss of ocular surface (OS) homeostasis characterizes the onset of dry eye disease. Resilience defines the ability to withstand this threat, reflecting the ability of the ocular surface to cope with and bounce back after challenging events. The coping capacity of the OS defines the ability to successfully manage cellular stress. Cellular stress, which is central to the outcome of the pathophysiology of dry eye disease, is characterized by intensity, continuity, and receptivity, which lead to the loss of homeostasis, resulting in a phase of autocatalytic dysregulation, an event that is not well-defined. To better define this event, here, we present a model providing a potential approach when homeostasis is challenged and the coping capacities have reached their limits, resulting in the stage of heterostasis, in which the dysregulated cellular stress mechanisms take over, leading to dry eye disease. The main feature of the proposed model is the concept that, prior to the initiation of the events leading to cellular stress, there is a period of intense activation of all available coping mechanisms preventing the imminent dysregulation of ocular surface homeostasis. When the remaining coping mechanisms and resilience potential have been maximally exploited and have, finally, been exceeded, there will be a transition to manifest disease with all the well-known signs and symptoms, with a shift to allostasis, reflecting the establishment of another state of balance. The intention of this review was to show that it is possibly the phase of heterostasis preceding the establishment of allostasis that offers a better chance for therapeutic intervention and optimized recovery. Once allostasis has been established, as a new steady-state of balance at a higher level of constant cell stress and inflammation, treatment may be far more difficult, and the potential for reversal is drastically decreased. Homeostasis, once lost, can possibly not be fully recovered. The processes established during heterostasis and allostasis require different approaches and treatments for their control, indicating that the current treatment options for homeostasis need to be adapted to a more-demanding situation. The loss of homeostasis necessarily implies the establishment of a new balance; here, we refer to such a state as allostasis.

The Enduring Experience in Dry Eye Diagnosis: A Non-Interventional Study Comparing the Experiences of Patients Living With and Without Sjögren's Syndrome.

INTRODUCTION: Previous studies have examined the patient experience regarding the diagnosis and management of dry eye disease (DED). The current study explored the ways in which the DED diagnostic pathway differs for those living with and without Sjögren's syndrome (SS), to identify aspects that influence the patient experience and associated quality of life (QoL). METHODS: An observational/descriptive, non-interventional, retrospective, self-reported online survey was conducted among adults living in France, Spain and Italy who were diagnosed with DED (with/without SS), were using topical DED treatments (≥ 6 months), and were not contact lens users. Recruitment was via an online database for non-SS participants and through local patient advocacy groups for SS respondents. RESULTS: The analysis included 827 respondents; 416 (50.3%) had SS and 82% were female. The mean age was 55 (SD 11; range 16-99) years. The mean age at diagnosis was 46 (SD 12; range 13-78) years and 50 (SD 10; range 21-73) years for SS and non-SS groups, respectively (p < 0.0001). The mean time to diagnosis was extended for SS participants [32 (SD 62) months] versus non-SS individuals [8.6 (SD 28) months (p < 0.0001)] and was associated with reduced QoL scores (r = 0.113; p = 0.0169). More SS participants (31%) consulted ≥ 4 healthcare professionals (HCPs) before DED diagnosis, versus non-SS individuals (6%) (p < 0.0001). Diagnosing clinician varied for SS respondents according to country, probably due to differences in healthcare systems/structures. More SS participants viewed their condition as a handicap than a discomfort, reporting greater QoL impact (p < 0.0001). CONCLUSIONS: Patient experiences in DED diagnosis vary substantially when comparing SS and non-SS individuals. Time to diagnosis significantly impacts QoL for SS patients, who see more HCPs ahead of DED diagnosis. The number of HCPs consulted before diagnosis and perceptions of DED are important for both groups. Country-specific variations highlight opportunities to improve consistency and efficiency across DED diagnostic pathways. These data should be considered alongside existing evidence from high-quality sources (e.g. clinical records).

High Molecular Weight Hyaluronan Promotes Corneal Nerve Growth in Severe Dry Eyes.

The purpose of this study was to investigate the effect of high molecular weight hyaluronan (HMWHA) eye drops on subbasal corneal nerves in patients suffering from severe dry eye disease (DED) and to evaluate the damage of subbasal corneal nerves associated with severe DED. Designed as an international, multicenter study, 16 patients with symptoms of at least an Ocular Surface Disease Index (OSDI) score of 33, and corneal fluorescein staining (CFS) of at least Oxford grade 3, were included and randomized into two study arms. The control group continued to use their individual optimum artificial tears over the study period of eight weeks; in the verum group, the artificial tears were substituted by eye drops containing 0.15% HMWHA. At the baseline visit, and after eight weeks, the subbasal nerve plexus of 16 patients were assessed by confocal laser scanning microscopy (CSLM). The images were submitted to a masked reading center for evaluation. Results showed a significant increase of total nerve fiber lengths (CNFL) in the HMWHA group (p = 0.030) when compared to the control group, where the total subbasal CNFL did not significantly change from baseline to week 8. We concluded that in severe DED patients, HMWHA from topically applied eye drops could cross the epithelial barrier and reach the subbasal nerve plexus, where it exercised a trophic effect.

The HYLAN M Study: Efficacy of 0.15% High Molecular Weight Hyaluronan Fluid in the Treatment of Severe Dry Eye Disease in a Multicenter Randomized Trial.

The aim of the HYLAN M study was to investigate if symptoms and/or signs of patients suffering from severe dry eye disease (DED) can be improved by substituting individually optimized artificial tear therapy by high molecular weight hyaluronan (HMWHA) eye drops. In this international, multicenter study, patients with symptoms of at least ocular surface disease index (OSDI) 33 and corneal fluorescein staining (CFS) of at least Oxford grade 3 were included. A total of 84 per-protocol patients were randomized in two study arms. The control group continued to use their individual optimum artificial tears over the study period of eight weeks; in the verum group, the artificial tears were substituted by eye drops containing 0.15% HMWHA. At the week 8 visit, the average OSDI of the verum group had improved by 13.5 as compared to the control group (p = 0.001). The best corrected visual acuity (BCVA) had improved by 0.04 logMAR (p = 0.033). CFS, tear film break-up time (TBUT), Schirmer I, lid wiper epitheliopathy (LWE), mucocutaneous junction (Yamaguchi score), and tear osmolarity were not significantly different between the verum and control groups (p > 0.050). We conclude that for most patients with severe DED, 0.15% HMWHA eye drops provide excellent improvement of symptoms without impairment of dry eye signs.

Impact of Attrition, Intercellular Shear in Dry Eye Disease: When Cells are Challenged and Neurons are Triggered.

The mechanical component in the pathophysiology of dry eye disease (DED) deserves attention as an important factor. The lubrication deficit induced impaired mechano-transduction of lid pressure to the ocular surfaces may lead to the dysregulation of homeostasis in the epithelium, with sensations of pain and secondary inflammation. Ocular pain is possibly the first sign of attrition and may occur in the absence of visible epithelial damage. Attrition is a process which involves the constant or repeated challenge of ocular surface tissues by mechanical shear forces; it is enhanced by the thinning of corneal epithelium in severe DED. As a highly dynamic process leading to pain and neurogenic inflammation, the identification of the impact of attrition and its potential pathogenic role could add a new perspective to the current more tear film-oriented models of ocular surface disease. Treatment of DED addressing lubrication deficiencies and inflammation should also consider the decrease of attrition in order to stimulate epithelial recovery and neural regeneration. The importance of hyaluronic acid, its molecular characteristics, the extracellular matrix and autoregulative mechanisms in this process is outlined. The identification of the attrition and recognition of its impact in dry eye pathophysiology could contribute to a better understanding of the disease and optimized treatment regimens.

The Effects of High Molecular Weight Hyaluronic Acid Eye Drop Application in Environmental Dry Eye Stress Model Mice.

Hyaluronic acid (HA) ophthalmic solution is widely used in dry eye treatment worldwide. However, there are no reports comparing the dry eye treatment effects of high molecular weight HA with low molecular weight HA. Sixty eight-week-old C57BL/6 mice were assigned to the following 6 groups and exposed to environmental dry eye stress (EDES) that mimics office work environment: 1) 0.1% low molecular weight HA (LMWHA) eye drops, 2) 0.3% LMWHA eye drops, 3) 3% diquafosol sodium (DQ) eye drops, 4) 0.15% high molecular weight HA (HMWHA) eye drops, 5) no treatment with exposure to EDES (EDES+/Treatment-), and 6) no treatment without exposure to EDES (EDES-/Treatment-). After EDES, the HMWHA group had significantly longer break-up time (BUT) than the 0.1%, 0.3% LMWHA groups and the DQ group. After EDES, the HMWHA group had significantly lower lissamine green staining scores than the LMWHA and DQ groups. Subepithelial presumed dendritic cell density in the HMWHA group was significantly lower than the EDES+/Treatment- group. After EDES exposure, Conjunctival Muc5AC mRNA expression in the HMWHA group was significantly higher than the 0.1 and 0.3% LMWHA groups. Ophthalmic HMWHA solution may have a better dry eye treatment effect than LMWHA or DQ solution, owing to its anti-inflammatory effect.

Osmokinetics: Defining the Characteristics of Osmotic Challenge to the Ocular Surface.

The association of severe dry eye disease with elevated osmolarity in the tear film is a subject of ongoing discussions. As the absolute value of osmolarity in tear film is highly variable, the daily variation in osmolarity (DVO) has recently been proposed to further identify the osmotic stress at the ocular surface. However, the DVO alone does not explain the variations in the available published data or allow their use in diagnostic testing or therapy. We therefore investigated and evaluated further details of osmokinetics and their importance for ocular surface disease on the basis of the available literature. Additionally, osmolarity was measured in the tear samples of volunteers in the morning hours between 8 - 10 a. m., midday noon-2 p. m., and afternoon between 3 - 5 p. m., i.e., during normal office hours. The results were compared with available published data which suggested that within the DVO, the daily maximal amplitude of osmotic variation (M-DVO) and the frequency of osmotic cycles (defined as daily osmolarity cycles, DOC) could be the main factors that further characterize osmokinetics. In addition, a decisive role could be the level of osmolarity at which the variation does occurs (L-DVO). The possible effects of these characteristics on ocular surface pathophysiology are discussed, along with their relationship to topical therapy with hypo-osmolar solutions, and the model of the osmotic roller coaster is introduced.

Hyaluronic Acid as an Alternative to Autologous Human Serum Eye Drops: Initial Clinical Results with High-Molecular-Weight Hyaluronic Acid Eye Drops.

INTRODUCTION: Autologous serum eye drops (ASED) are used in the treatment of most severe stages of dry eye. Once introduced, it is currently considered impossible to return to other lubricating eye drops or other commercially available therapeutic regimen. MATERIALS AND METHODS: In a randomized study, non-preserved high-molecular-weight hyaluronic acid eye drops were offered as an alternative to 11 patients using autologous serum treatment for at least 3 months. The control group (n = 5) continued their treatment with ASED. The verum group (n = 6) used very-high-molecular-weight hyaluronic eye drops (Comfort Shield®) instead of the ASED. RESULTS: From four of initially six patients in the verum group that finished the study, 2 (50%) preferred to stay with the very-high-molecular-weight hyaluronic acid eye drops beyond the trial period, the other two returned to the earlier therapy with ASED. The control group continued their treatment as before and finished the study after 8 weeks. CONCLUSION: For the first time, artificial eye drops, i.e., high-molecular-weight hyaluronic acid eye drops, offered an acceptable alternative to ASED. Some patients perceived these drops as even better than the patient's own serum. This is the first evidence that optimization of the molecular structure of hyaluronic acid can be used to create eye drops that are perceived to be better than other tested tear substitutes and even patients' own serum. This offers a new treatment perspective for patients with very severe dry eye disease.

Reconsidering the central role of mucins in dry eye and ocular surface diseases.

Mucins are key actors in tear film quality and tear film stability. Alteration of membrane-bound mucin expression on corneal and conjunctival epithelial cells and/or gel-forming mucin secretion by goblet cells (GCs) promotes in ocular surface diseases and dry eye disease (DED). Changes in the mucin layer may lead to enhanced tear evaporation eventually contributing to tear hyperosmolarity which has been associated with ocular surface inflammation. Inflammatory mediators in turn may have a negative impact on GCs differentiation, proliferation, and mucin secretion. This sheds new light on the position of GCs in the vicious circle of DED. As contributor to ocular surface immune homeostasis, GC loss may contribute to impaired ocular surface immune tolerance observed in DED. In spite of this, there are no tools in routine clinical practice for exploring ocular surface mucin deficiency/dysregulation. Therefore, when selecting the most appropriate treatment options, there is a clear unmet need for a better understanding of the importance of mucins and options for their replacement. Here, we comprehensively revisited the current knowledge on ocular surface mucin biology, including functions, synthesis, and secretion as well as the available diagnostic tools and treatment options to improve mucin-associated homeostasis. In particular, we detailed the potential link between mucin dysfunction and inflammation as part of the uncontrolled chronic inflammation which perpetuates the vicious circle in DED.

Clinical impact of inflammation in dry eye disease: proceedings of the ODISSEY group meeting.

Dry eye disease (DED) is a common, multifactorial ocular condition with major impact on vision and quality of life. It is now well recognized that the pathophysiology of chronic DED can include a cycle of inflammation involving both innate and adaptive immune responses. Recently, in vitro/in vivo models have been used to obtain a better understanding of DED-related inflammatory processes at molecular/cellular levels although they do not truly reproduce the complex and chronic hallmarks of human DED. In clinical DED research, advanced techniques such as impression cytology, conjunctival biopsy, in vivo confocal microscopy and multiplex tear analyses have allowed an improved assessment of inflammation in DED patients. This was supported by the identification of reliable inflammatory markers including matrix metalloproteinase-9, human leucocyte antigen-DR or intercellular adhesion molecule-1 in tears and impression cytology samples. One of the current therapeutic strategies focuses on breaking the inflammatory cycle perpetuating the ocular surface disease, and preclinical/clinical research has led to the development of promising anti-inflammatory compounds. For instance, cyclosporine, already approved in the United States, has recently been authorized in Europe to treat DED associated with severe keratitis. In addition, other agents such as corticosteroids, doxycycline and essential fatty acids, through their anti-inflammatory properties, show encouraging results. We now have a clearer understanding of the inflammatory processes involved in DED, and there is hope that the still emerging preclinical/clinical findings will be translated into new and highly effective therapies for patients in the near future.

Comparison of the performance and safety of 2 ophthalmic viscosurgical devices in cataract surgery.

PURPOSE: To compare the clinical performance and safety of 2 ophthalmic viscosurgical devices (OVDs)-Twinvisc (OVD 1) and Duovisc (OVD 2)-in cataract surgery. SETTING: European multicenter study. DESIGN: Prospective randomized controlled study. METHODS: Patients with cataract had phacoemulsification and intraocular lens implantation in 1 eye. They were randomly assigned to receive OVD 1 or OVD 2. Preoperative and postoperative examinations over 3 months included mean intraocular pressure (IOP), incidence of IOP peaks (≥30 mm Hg and ≥24 mm Hg), endothelial cell count (ECC), corneal thickness, and intraocular inflammation. A subjective evaluation of the OVDs was performed. RESULTS: The study comprised 220 patients. The incidence of IOP peaks and the mean IOP were not statistically significantly different between the 2 groups at any of the follow-up visits. At 6 hours, the incidence of IOP spikes 30 mm Hg or higher was 6.5% and 7.2% in the OVD 1 and the OVD 2 groups, respectively (P = .846). For the IOP spikes 24 mm Hg or higher, the incidence was 16.8% and 25.2%, respectively (P = .128). Three months postoperatively there was no statistically significant difference in ECC and pachymetry between the 2 groups. Mild inflammation was noticed up to 7 days postoperatively after which it resolved in both groups. Subjectively, the OVD 2 was easier to use, whereas the OVD 1 had better cohesive and dispersive properties. CONCLUSIONS: Both OVDs have similar performance and safety profiles in phacoemulsification cataract surgery. No clinically relevant differences were found between the 2 devices regarding transient IOP spikes, mean IOP, corneal endothelium injury, or inflammation.

Patients' perception of DED and its relation with time to diagnosis and quality of life: an international and multilingual survey.

BACKGROUND/AIMS: To improve understanding of patients' experience and perception of dry eye disease (DED) and its impact on quality of life (QoL). METHODS: This survey was observational, non-interventional and cross-sectional. The survey was conducted online on 706 patients with DED from five European countries (France, Germany, Italy, Spain and the UK). All patients met the following inclusion criteria: 40 years or older with DED diagnosed by a healthcare professional (HCP), not wearing contact lenses and using tear substitutes daily for at least 6 months. The survey (performed in the five native languages) included 9 screening questions (inclusion criteria) and 26 complementary questions about patients' demography, disease history, DED diagnosis, use of relief treatments, perceptions of DED condition and its impact on QoL. RESULTS: Overall, 218 of 706 (31%) patients perceived DED as a 'disease' or even a 'handicap', and 468 of 706 (66%) as a 'discomfort'. High impact of DED on patients' QoL was associated with negative perception, delay in diagnosis, visits to more than one HCP before diagnosis and high frequency of treatment use. This survey also provided us with a list of language-specific keywords that patients used most frequently to spontaneously describe their condition. CONCLUSIONS: Findings showed that negative perception of DED, delayed diagnosis and high frequency of treatment use were inter-related, and that all have a negative impact on patients' QoL. The generated language-specific keywords used to describe DED could serve as the basis for a comprehensive QoL questionnaire to be used in clinical settings.

Immunohistochemical Detection of CTGF in the Human Eye.

Purpose/Aim of the study: Connective tissue growth factor (CTGF) is a key player in the control of extracellular matrix remodeling, fibrosis, and angiogenesis. It is also involved in the modification of the trabecular meshwork, thus potentially modulating outflow facility and intraocular pressure (IOP). As a consequence, CTGF might be relevant for the development of elevated IOP, a major risk factor in glaucoma-pathogenesis. While comprehensive information on the origins of CTGF in the human eye is not available, the goal of this study is to identify ocular sources of CTGF using morphological methods. MATERIALS AND METHODS: Human donor eyes were prepared for immunohistochemical analysis of CTGF, α-smooth muscle-actin (ASMA), and CD31. Confocal laser scanning microscopy was used for documentation. RESULTS: In the cornea, CTGF-immunoreactivity (CTGF-IR) was detected in the epithelium, mainly in basal layers, stromal keratinocytes, and endothelial cells. Adjacent conjunctiva showed also CTGF-IR in epithelial cells. In the iris, both, the sphincter and dilator muscles displayed CGTF-IR, as did iris and ciliary body vessels, deriving at this location from the vascular endothelium, as detected with CD31, but not from vascular smooth muscle cells, as detected with ASMA. In the ciliary body, CTGF-IR was detected in smooth-muscle cells of the ciliary muscle and further in the non-pigmented epithelium. In the retina, CTGF-IR was detected in the NFL and weakly in the IPL/OPL. In the choroid, the choriocapillaris and blood vessels displayed CTGF-IR. Further, few cells in the optic nerve head and the lamina cribrosa were CTGF-positive. CONCLUSION: CTGF was detected in various structures of the human eye. Since CTGF has been also described in aqueous humor, the identified structures might be the sources of CTGF in the aqueous humor. By means of aqueous flow, CTGF is transported into the trabecular meshwork, where it could change outflow facility and therefore affecting IOP homeostasis.

Efficacy and safety of 0.1% cyclosporine A cationic emulsion in the treatment of severe dry eye disease: a multicenter randomized trial.

PURPOSE: The SANSIKA study was conducted to assess the treatment effect of 0.1% cyclosporine A cationic emulsion (CsA CE) eye drops on signs and symptoms of patients with severe dry eye disease (DED). METHODS: This was a multicenter, randomized, double-masked, 2-parallel-arm, 6-month phase III study with a 6-month open-label treatment safety follow-up. Patients with severe DED with corneal fluorescein staining (CFS) grade 4 on the modified Oxford scale were randomized to receive once-daily CsA CE (Ikervis®) or its vehicle. RESULTS: A total of 246 patients were randomized. The proportion of patients achieving ≥2 grades improvement in CFS and a 30% improvement in symptoms (Ocular Surface Disease Index [OSDI]) by month 6 was 28.6% with CsA CE vs 23.1% with vehicle (p = 0.326) (primary endpoint). Assessment of corneal damage showed greater improvement with CsA CE over vehicle in mean adjusted CFS change from baseline to month 6 (-1.764 vs -1.418, p = 0.037). There was a reduction in ocular surface inflammation assessed by human leukocyte antigen DR expression in favor of CsA CE at month 6 (p = 0.021). The mean OSDI change from baseline was -13.6 with CsA CE and -14.1 with vehicle at month 6 (p = 0.858). The main adverse event was instillation site pain (29.2% vs 8.9% in the CsA CE and vehicle groups, respectively), and it was mostly mild. CONCLUSIONS: CsA CE was well-tolerated and effective in improving corneal damage and ocular surface inflammation and confirmed the positive benefit-risk ratio of this new formulation of CsA for the treatment of severe keratitis in DED.

Evidence of seasonality and effects of psychrometry in dry eye disease.

PURPOSE: Current models consider the development of dry eye disease (DED) as a more or less continuous process with only minor daily variations. Clinical evidence, however, does suggest the existence of phase-like recurring dry eye complaints that may be linked to seasonal environmental conditions. In this survey-based study, we examined the influence of seasonality in dry eye pathophysiology. METHODS: A specific protocol for a telephone interview was created. Then, 738 patients suffering from dry eye and/or Sjögren's syndrome were interviewed and asked about the impact of the four seasons and other weather conditions on their ocular symptoms. Data were statistically analysed. All data were compared in respect to the relation between season, gender, country of origin and the presence of comorbidities. RESULTS: Overall, 47% of respondents stated that seasonal conditions had a high impact on their DED symptoms, with only 15% reporting that there was no seasonal impact on their symptoms. Wind was the most commonly reported weather condition to impact dry eye symptoms (for 71% of patients), followed by sunshine (60%) and heat (42%). Cold weather was also reported to aggravate dry eye sensation by 34% of patients. The two seasons most commonly associated with dry eye complaints were summer and winter (for 51% and 43% of patients, respectively). Only 8% stated that no weather conditions affected their symptoms. DISCUSSION: This study confirms the seasonal enhancement of dry eye sensations and symptoms. Environmental characteristics such as cold and heat as well as wind were the most commonly cited triggering factors. Geographical differences do exist between the countries surveyed and the seasonal peak of complaints appears related to temperature and humidity. The main seasons of dry eye complaints in Europe were winter and summer. Such seasonal characteristics in ocular surface disease should be kept in mind when considering diagnosis and treatment as well when investigating the ocular surface. CONCLUSION: Our study confirmed high prevalence of both seasonal and weather-related enhancement of dry eye sensations and symptoms.