The mission of the Tear Film & Ocular Surface Society (TFOS) is to advance the research, literacy, and educational aspects of the scientific field of the tear film and ocular surface. Fundamental to fulfilling this mission is the TFOS Global Ambassador program. TFOS Ambassadors are dynamic and proactive experts, who help promote TFOS initiatives, such as presenting the conclusions and recommendations of the recent TFOS DEWS II™, throughout the world. They also identify unmet needs, and propose future clinical and scientific solutions, for management of ocular surface diseases in their countries. This meeting report addresses such needs and solutions for 25 European countries, as detailed in the TFOS European Ambassador meeting in Rome, Italy, in September 2019.

Most irreversible blindness results from retinal disease. To advance our understanding of the etiology of blinding diseases, we used single-cell RNA-sequencing (scRNA-seq) to analyze the transcriptomes of ~85,000 cells from the fovea and peripheral retina of seven adult human donors. Utilizing computational methods, we identified 58 cell types within 6 classes: photoreceptor, horizontal, bipolar, amacrine, retinal ganglion and non-neuronal cells. Nearly all types are shared between the two retinal regions, but there are notable differences in gene expression and proportions between foveal and peripheral cohorts of shared types. We then used the human retinal atlas to map expression of 636 genes implicated as causes of or risk factors for blinding diseases. Many are expressed in striking cell class-, type-, or region-specific patterns. Finally, we compared gene expression signatures of cell types between human and the cynomolgus macaque monkey, Macaca fascicularis. We show that over 90% of human types correspond transcriptomically to those previously identified in macaque, and that expression of disease-related genes is largely conserved between the two species. These results validate the use of the macaque for modeling blinding disease, and provide a foundation for investigating molecular mechanisms underlying visual processing.

: Fasanella-Servat operation (FSO) was previously reported to be associated with post-operative dry eyes due to accessory lacrimal gland resection during the surgery.We performed a retrospective, cohort study to determine the frequency of lacrimal tissue resection during FSO and its correlation with post-operative eye dryness and keratopathy.: Review of all patients who underwent FSO at New York-Presbyterian Weill Cornell Hospital over a two-year period (2013-2015). Patients were included only if they had adequate histopathological specimens of the resected tissue obtained during surgery. Outcomes included the study of the pathological specimen for the presence of lacrimal tissue; Post-operative dry eye symptoms and pre- and post-operative corneal epitheliopathy.: 46 patients with a total of 58 eyelid resections were studied.Eight eyelids (13.7%) were found to have lacrimal tissue present in the pathology specimens.Postoperatively, nine patients reported some symptoms of dry eye and new-onset keratopathy was noted in four eyes (6.8%), only one of which had lacrimal tissue present in histopathology specimen obtained from surgery.: Previous studies found lacrimal tissue present in up to 43% of specimens resected during FSO. Our data found a lower rate of lacrimal tissue resection during FSO, and did not find an association between lacrimal tissue resection and post-operative dryness or epitheliopathy.: Our study is one of few to examine histopathological resections from the FSO.We found that lacrimal tissue is not frequently resected during FSO, and when it is resected, there is no increased incidence of post-operative dryness or keratopathy.

PURPOSE: To evaluate corneal immune dendritiform cell (DC) changes in dry eye disease (DED) using in vivo confocal microscopy (IVCM) and to correlate IVCM parameters with clinical severity. METHODS: This was a retrospective, cross-sectional study including 300 eyes of 150 DED patients and 49 eyes of 49 age-matched controls. Severity of DED was based on the Dry Eye Workshop (DEWS) classification. IVCM images of subbasal layer of the central cornea were analyzed for DC density and morphology (including number of dendrites per DC, DC size and DC field). RESULTS: DC density was significantly higher in DED compared to controls (93.4 ± 6.3 vs. 25.9 ± 3.9 cells/mm; P < 0.001). Morphologically, number of dendrites, DC size and field were significantly larger in DED (3.3 ± 0.1, 106.9 ± 4.7 μm, 403.8 ± 20.1 μm than controls (2.3 ± 0.1, 62.5 ± 5.7 μm, 241.4 ± 24.4 μm, P < 0.001). Significantly higher DC density compared to controls was observed as early as Level 1 DED severity (87 ± 10 cells/mm, p < 0.001. Significant morphological changes in DC were detected for Levels 2 to 4 (p=<0.001, and p =< 0.05) for dendrites and DC field, respectively. Similarly, DC size showed significant increase at DED level 3-4. (p < 0.05). Linear regression analysis showed that both conjunctival and corneal staining were independently associated with DC density, while corneal staining was independently associated with DC morphology. CONCLUSION: DC density and morphology correlated with clinical severity of DED. While, DC density is increased in mild DED, morphological changes are seen only in severe cases. IVCM may be a powerful tool to detect early immune changes and may complement clinical examination in DED.

Corneal dystrophies are broadly defined as inherited disorders that affect any layer of the cornea and are usually progressive, bilateral conditions that do not have systemic effects. The 2015 International Classification of Corneal Dystrophies classifies corneal dystrophies into four classes: epithelial and subepithelial dystrophies, epithelial-stromal TGFBI dystrophies, stromal dystrophies and endothelial dystrophies. Whereas some corneal dystrophies may result in few or mild symptoms and morbidity throughout a patient's lifetime, others may progress and eventually result in substantial visual and ocular disturbances that require medical or surgical intervention. Corneal transplantation, either with full-thickness or partial-thickness donor tissue, may be indicated for patients with advanced corneal dystrophies. Although corneal transplantation techniques have improved considerably over the past two decades, these surgeries are still associated with postoperative risks of disease recurrence, graft failure and other complications that may result in blindness. In addition, a global shortage of cadaveric corneal graft tissue critically limits accessibility to corneal transplantation in some parts of the world. Ongoing advances in gene therapy, regenerative therapy and cell augmentation therapy may eventually result in the development of alternative, novel treatments for corneal dystrophies, which may substantially improve the quality of life of patients with these disorders.

Uveitis is characterized by intraocular inflammation involving the uveal tract; its etiologies generally fall into two broad categories: autoimmune/inflammatory or infectious. Corticosteroids  are a powerful and important class of medications ubiquitous in the treatment of uveitis. They may be given systemically or locally, in the form of topical drops, periocular injection, intravitreal suspension, or intravitreal implant. This review describes each of the currently available corticosteroid treatment options for uveitis, including favorable and unfavorable characteristics of each as well as applicable clinical trials. The main advantage of corticosteroids as a whole is their ability to quickly and effectively control inflammation early on in the course of uveitis. However, they can have serious side effects, whether localized to the eye (such as cataract and elevated intraocular pressure) or systemic (such as osteonecrosis and adrenal insufficiency) and in the majority of cases of uveitis are not an appropriate option for long-term therapy.

PURPOSE: To estimate the incidence of medication-free remission of chronic anterior uveitis and identify predictors thereof. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients diagnosed with anterior uveitis of longer than 3 months' duration followed up at United States tertiary uveitis care facilities. METHODS: Estimation of remission incidence and identification of associated predictors used survival analysis. MAIN OUTCOME MEASURES: Incidence of medication-free remission. For the primary analysis, remission was defined as inactive uveitis while off treatment at all visits spanning an interval of at least 90 days or-for patients who did not return for follow-up after 90 days-remaining inactive without receiving suppressive medications at all of the last visits. Association of factors potentially predictive of medication-free remission was also studied. RESULTS: Two thousand seven hundred ninety-five eyes of 1634 patients with chronic anterior uveitis were followed up over 7936 eye-years (4676 person-years). The cumulative medication-free, person-year remission incidence within 5 years was 32.7% (95% confidence interval [CI], 30.4%-35.2%). Baseline clinical factors predictive of reduced remission incidence included longer duration of uveitis at presentation (for 2 to 5 years vs. less than 6 months: adjusted hazard ratio [aHR], 0.61; 95% CI, 0.44-0.83), bilateral uveitis (aHR, 0.75; 95% CI, 0.59-0.96), prior cataract surgery (aHR, 0.70; 95% CI 0.56-0.88), and glaucoma surgery (aHR, 0.63; 95% CI, 0.45-0.90). Two time-updated characteristics were also predictive of reduced remission incidence: keratic precipitates (aHR, 0.36; 95% CI, 0.21-0.60) and synechiae (aHR, 0.62; 95% CI, 0.41-0.93). Systemic diagnosis with juvenile idiopathic arthritis and spondyloarthropathy were also associated with reduced remission incidence. Older age at presentation was associated with higher incidence of remission (for age ≥40 years vs. <40 years: aHR, 1.29; 95% CI, 1.02-1.63). CONCLUSIONS: Approximately one third of patients with chronic anterior uveitis remit within 5 years. Longer duration of uveitis, younger age, bilateral uveitis, prior cataract surgery, glaucoma surgery, presence of keratic precipitates and synechiae, and systemic diagnoses of juvenile idiopathic arthritis and spondyloarthropathy predict reduced remission incidence; patients with these factors should be managed taking into account the higher probability of a longer disease course.

Epithelial-mesenchymal transition (EMT) and endothelial-mesenchymal transition (EndMT) are physiological processes required for normal embryogenesis. However, these processes can be hijacked in pathological conditions to facilitate tissue fibrosis and cancer metastasis. In the eye, EMT and EndMT play key roles in the pathogenesis of subretinal fibrosis, the end-stage of age-related macular degeneration (AMD) that leads to profound and permanent vision loss. Predominant in subretinal fibrotic lesions are matrix-producing mesenchymal cells believed to originate from the retinal pigment epithelium (RPE) and/or choroidal endothelial cells (CECs) through EMT and EndMT, respectively. Recent evidence suggests that EMT of RPE may also be implicated during the early stages of AMD. Transforming growth factor-beta (TGFβ) is a key cytokine orchestrating both EMT and EndMT. Investigations in the molecular mechanisms underpinning EMT and EndMT in AMD have implicated a myriad of contributing factors including signaling pathways, extracellular matrix remodelling, oxidative stress, inflammation, autophagy, metabolism and mitochondrial dysfunction. Questions arise as to differences in the mesenchymal cells derived from these two processes and their distinct mechanistic contributions to the pathogenesis of AMD. Detailed discussion on the AMD microenvironment highlights the synergistic interactions between RPE and CECs that may augment the EMT and EndMT processes in vivo. Understanding the differential regulatory networks of EMT and EndMT and their contributions to both the dry and wet forms of AMD can aid the development of therapeutic strategies targeting both RPE and CECs to potentially reverse the aberrant cellular transdifferentiation processes, regenerate the retina and thus restore vision.

PURPOSE: To validate a comprehensive clinical algorithm for the assessment and treatment of microbial keratitis (MK). DESIGN: Retrospective cohort study. METHODS: The "1, 2, 3 Rule" for the initial management of MK was conceived by Vital and associates in 2007 to inform the decision as to when to perform corneal cultures. The rule is invoked when any 1 of 3 clinical parameters is met: ≥1+ anterior chamber cells, ≥2 mm infiltrate, or infiltrate ≤3 mm distance from the corneal center. When the rule is met, we added the mandatory use of fortified topical antibiotics after cultures are obtained. We compared outcomes of cases presenting to Massachusetts Eye and Ear 2 years before (Group I, n = 665) and after (Group II, n = 767) algorithm implementation. The primary composite outcome was a vision-threatening complication, such as corneal perforation. RESULTS: At a median follow-up of 67.0 and 60.0 days, respectively, 172 patients experienced a vision-threatening complication (Group I, 12.9% vs Group II, 11.2%, P = .51). While the algorithm codified conventional management practice at either end of disease severity, the effect of algorithm-augmented care was best appreciated in patients with lesions satisfying only 1 criterion. In this group, there was an increase in the proportion of patients undergoing culture at presentation (54.6% vs 67.7%, P = .006), fortified antibiotic prescription (29.7% vs 53.9%, P < .001), and reduction in vision-threatening complications (9.7% vs 1.8%, P = .001). The proportion of patients who were not cultured at presentation but later required culturing decreased (13.4% vs 5.1%, P = .001), as did patients who did not meet any criteria but were nonetheless cultured (23.9% vs 8.5%, P < .001). Multiple logistic regression showed that all algorithm parameters were independently associated with outcome: ≥1+ anterior chamber cells (odds ratio [OR] 1.66, 95% confidence interval 1.09-2.52); ≥2 mm infiltrate (OR 4.74, 2.68-8.40); and ≤3 mm from corneal center (OR 2.82, 1.85-4.31), confirmed with comparison to a bootstrapped sample (n = 10,000). CONCLUSIONS: The implementation of this algorithm reduced vision-threatening complications for patients with lesions satisfying only 1 criterion, arguably the most difficult patients in whom to judge disease severity. Implementation also led to a decrease in patients receiving unnecessary care.

PRECIS: In a cohort study of 120,307 participants with 25+ years of follow-up, a history of nonmelanoma skin cancer (NMSC) was associated with a 40% higher exfoliation glaucoma (XFG) risk. PURPOSE: The purpose of this study was to evaluate the relationship between NMSC (a marker of ultraviolet radiation exposure) and XFG. METHODS: We performed a cohort study of US women (n=79,102; 1980-2014) and men (n=41,205; 1986-2014), aged 40+ years and at risk for glaucoma who reported eye examinations. From 1984 (women)/1988 (men), we asked about basal cell carcinoma or squamous cell carcinoma history separately; in prior years, we asked about any NMSC history in a single question. Squamous cell carcinoma was confirmed with histopathology reports while basal cell carcinoma and any early (<1984/<1988) NMSC history was self-reported. Incident XFG cases (362 women and 83 men) were confirmed with medical records. Using pooled data, we estimated multivariable-adjusted relative risks [MVRRs; 95% confidence intervals (CIs)] with Cox proportional hazards models that were stratified by age (in mo), 2-year time period at risk and average lifetime residential latitude. RESULTS: In multivariable-adjusted analyses, we observed a 40% higher XFG risk with any NMSC history (MVRR=1.40; 95% CI=1.08-1.82); the association was observed even with 4 and 8-year lags in NMSC history. Also, the NMSC association was stronger in younger (below 65 y; MVRR=2.56; 95% CI=1.62-4.05) versus older participants (65 y and above; MVRR=1.25; 95% CI=0.94-1.66; P for interaction=0.01) and those living in the northern latitudes (≥42°N; MVRR=1.92; 95% CI=1.28-2.88) versus more southern latitudes (<42°N; MVRR=1.19; 95% CI=0.86-1.66; P for interaction=0.04). CONCLUSION: NMSC was associated with higher XFG risk, particularly among younger participants and those living in the Northern US.