Cell-free DNA concentration and fragment size fraction correlate with FDG PET/CT-derived parameters in NSCLC patients.

PURPOSE: The aim of our study was to investigate the correlation between cfDNA concentration and fragment size fraction with FDG PET/CT- and CT-derived parameters in untreated NSCLC patient. METHODS: Fifty-three patients diagnosed of locally advanced or metastatic NSCLC who had undergone FDG PET/CT, CT and cfDNA analysis prior to any treatment were included in this retrospective study. CfDNA concentration was measured by fluorometry and fragment size fractions were determined by microchip electrophoresis. [18F]F-FDG PET/CT was performed and standardised uptake values (SUV), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) were calculated for primary, extrapulmonary and total disease. CT scans were evaluated according to RECIST 1.1 criteria. RESULTS: CfDNA concentration showed a positive correlation with extrapulmonary MTV (r2 = 0.36, P = 0.009), and extrapulmonary TLG (r2 = 0.35, P = 0.009) and their whole-body (wb) ratios. Higher concentrations of total cfDNA were found in patients with liver lesions. Short fragments of cfDNA (100-250 bp) showed a positive correlation with extrapulmonary MTV (r2 = 0.49, P = 0.0005) and extrapulmonary TLG (r2 = 0.39, P = 0.006) and their respective wb ratios, and a negative correlation with SUVmean (r2 = -0.31, P = 0.03) and SUVmean/SUVmax ratio (r2 = -0.34, P = 0.02). A higher fraction of short cfDNA fragments was found in patients with liver and pleural lesions. CONCLUSIONS: This study supports the hypothesis that cfDNA concentration and short cfDNA fragment size fraction reflect the tumour burden as well as metabolic activity in advanced NSCLC patients. This suggests their suitability as complementary tests for a more accurate diagnosis of tumour metabolic behaviour and to allow personalised therapies.

Combined hyperosmolarity and inflammatory conditions in stressed human corneal epithelial cells and macrophages to evaluate osmoprotective agents as potential DED treatments.

PURPOSE: To develop an easy-to-perform combined model in human corneal epithelial cells (HCECs) and Balb/c mice macrophages J774.A1 (MP) for preliminary screening of potential ophthalmic therapeutic substances. METHODS: HCECs were exposed to different osmolarities (350-500 mOsm/L) and MTT assay was employed for cell survival and flow cytometry to assess apoptosis-necrosis and relative cell size (RCS) distribution. Effectiveness of Betaine, L-Carnitine, Taurine at different concentrations (ranging from 20 mM to 200 mM) was studied. Also, mucoadhesive polymers such as Hyaluronic acid (HA) and Hydroxypropylmethylcellulose (HPMC) (0.4 and 0.8%) were evaluated. Cells were pre-incubated with the compounds (8h) and then exposed to hyperosmotic stress (470 mOsm/L) for 16h. Moreover, anti-inflammatory activity was performed in LPS-stimulated MP. RESULTS: Exposure to hyperosmotic solutions between 450 and 500 mOsm/L promoted the highest cell death after 16h exposures (p < 0.0001) with a drop in viability to 34.96% ± 11.77 for 470 mOsm/L. Pre-incubation with Betaine at 150 mM and 200 mM provided the highest cell survival against hyperosmolarity (66.01% ± 3.65 and 65.90% ± 0.78 respectively) while HA 0.4% was the most effective polymer in preventing cell death (42.2% ± 3.60). Flow cytometry showed that Betaine and Taurine at concentrations between 150-200 mM and 20-80 mM respectively presented the highest anti-apoptotic activity. Also, HA and HPMC polymers reduced apoptotic-induced cell death. All osmoprotectants modified RCS, and polymers increased their value over 100%. L-Carnitine 50 mM, Taurine 40 mM and HA 0.4% presented the highest TNF-α inhibition activity (60%) albeit all of them showed anti-inflammatory inhibition percentages higher than 20% CONCLUSIONS: HCECs hyperosmolar model combined with inflammatory conditions in macrophages allows the screening of osmoprotectants by simulating chronic hyperosmolarity (16h) and inflammation (24h).

Realized niche and spatial pattern of native and exotic halophyte hybrids.

Interspecific hybridization is an important and common evolutionary mechanism, but field-based evaluations of changes in realized niches and zonation patterns of native and exotic hybrids relative to those of their parental plant species are rare. Would native hybrids forming hybrid zones between their parental species show realized niches similar to that of their parents, whereas would exotic hybrids show larger realized niches than their parents, and alter zonation patterns of native species? To address these questions, we examined key sediment characteristics in plots representing realized niches of native Sarcocornia hybrids, invasive Spartina hybrids and parental species in 14 salt marshes from four estuaries in the Gulf of Cadiz, Southwest Iberian Peninsula. In one representative marsh, the presence of plant taxa relative to intertidal plant zonation was recorded. Results documented that native and fertile hybrids of Sarcocornia had similar realized niche dimensions as their parental species and co-occurred with other plant species, supporting community diversity. However, exotic sterile hybrids of Spartina had realized niche dimensions lower than those of their parental species and occurred in monocultures. The native hybrids played a community structuring role, whereas the exotic Spartina hybrids were a disruptive influence that changed native halophyte zonation pattern and decreased diversity. This negative functional role could intensify if the sterile hybrids evolve and become fertile. Our study suggests the ecological niche dimension concept is an important tool for understanding species roles in ecosystems, incorporating many ideas from the individual to ecosystem levels.

Pyometra and unilateral uterine horn torsion in a sheep.

A 13-year-old Romanov sheep presented for evaluation of vaginal discharge, depression and anorexia. Blood work demonstrated mature neutrophilia and marked hyperlactatemia. Transrectal and transabdominal ultrasound revealed echogenic fluid (pus) within the uterus. Purulent uterine fluid culture yield Escherichia coli. A diagnosis of pyometra was made. After medical treatment without clinical improvement, an exploratory laparotomy was performed, and a 360-degree uterine left horn torsion was identified with the pyometra and multiple corpora lutea on both ovaries. Ovariohysterectomy was performed and the ewe recovered uneventfully.

Consensus document on allergic conjunctivitis (DECA).

Allergic conjunctivitis (AC) is an inflammatory disease of the conjunctiva caused mainly by an IgE-mediated mechanism. It is the most common type of ocular allergy. Despite being the most benign form of conjunctivitis, AC has a considerable effect on patient quality of life, reduces work productivity, and increases health care costs. No consensus has been reached on its classification, diagnosis, or treatment. Consequently, the literature provides little information on its natural history, epidemiological data are scarce, and it is often difficult to ascertain its true morbidity. The main objective of the Consensus Document on Allergic Conjunctivitis (Documento dE Consenso sobre Conjuntivitis Alérgica [DECA]), which was drafted by an expert panel from the Spanish Society of Allergology and Spanish Society of Ophthalmology, was to reach agreement on basic criteria that could prove useful for both specialists and primary care physicians and facilitate the diagnosis, classification, and treatment of AC. This document is the first of its kind to describe and analyze aspects of AC that could make it possible to control symptoms.

Dry eye disease pathogenesis and clinical signs: searching for correspondence in the clinical practice.

BACKGROUND: Ocular surface alterations causing dry eye disease (DED) can be described as a vicious circle consisting of different consecutive stages. Among the factors involved, the ocular surface immune-inflammatory response has been established as a key player in the pathogenesis of the vicious circle of DED. Thus, the prompt recognition of the disruption of the immunoregulatory mechanisms is crucial for properly managing the ocular surface alterations. To increase awareness and knowledge of the identification and clinical interpretation of immunological mechanisms of dry eye in clinical practice, we present two clinical cases related to DED patients to provide a practical example of clinical examination application and interpretation of diagnostic parameters in daily practice. Moreover, a literature overview of the available clinical examinations to assess the immunological involvement in DED patients, with a particular focus on the correlation between diagnostic parameters and pathogenesis of clinical signs, is provided with an educational intent. CASE PRESENTATION: The presented clinical experiences suggested that in ocular surface pathologies, knowledge of the immune-inflammatory pathogenetic mechanisms underlying the observed clinical sign is of great help for understanding what is being observed in the patient and, consequently, for the choice of appropriate therapy. Literature evidence suggests that many different clinical examinations can be used to assess inflammation in DED patients, such as the assessment of hyperemia, staining of the ocular surface and measurement of hyperosmolarity and MMP-9 levels. The combination of impression cytology and flow cytometry to assess for markers of inflammation is considered the best technique to quantify the level of inflammation on the ocular surface, even if not always applicable in clinical practice. CONCLUSIONS: Literature evidence and clinical experiences suggest that basic diagnostic approaches (assessment of hyperemia, MMP-9 levels, and staining of the ocular surface with Lissamine green or fluorescein) represent useful tools to assess the inflammatory component of DED in everyday practice, providing a guide to establish the correct therapeutic strategy.

IMPULSE Study: Impact of COVID-19 in the present of ophthalmology focusing on ocular surface and future trends.

INTRODUCTION AND OBJECTIVE: Digital evolution represents an opportunity for ophthalmology to adapt to new care models. This study aimed to find out how the pandemic has modified the clinical practice and training activities of the ophthalmologist specialised in ocular surface, as well as to analyse emerging trends and needs. MATERIALS AND METHODS: This study was carried out through an online survey. A committee of 3 specialists developed a questionnaire of 25 questions structured in: 1) Participant profile; 2) Impact of the pandemic on patient management and professional activities; 3) Trends and needs. RESULTS: 68 clinical ophthalmologists participated. There was a high degree of agreement (90%) that the pandemic has delayed ophthalmological follow-up visits and diagnosis. The participants agreed that the frequency of patients with dry eye disease (75%), stye/chalazion (62%) and blepharitis (60%) has increased. According to 28%, remote monitoring of pathologies such as dry eye, glaucoma, diabetes, conjunctivitis, hyposphagmas, styes, etc., will be common, especially in the young population. This will be especially relevant in chronic or mild pathologies of the ocular surface, and in the follow-up of patients after cataract and diabetic retinopathy interventions. CONCLUSIONS: During the pandemic, an increase in the incidence of certain ocular surface diseases has been perceived. The telematic follow-up of chronic or mild pathologies of the ocular surface entails the need to provide specific training for both the patient and the healthcare professional, in addition to screening and referral protocols that would optimise the flow of care.

[IMPULSE Study: Impact of COVID-19 in the present of ophthalmology focusing on ocular surface and future trends]. / Estudio IMPULSO: impacto de la COVID-19 en el presente de la oftalmología centrada en superficie ocular y tendencias de futuro.

Background and objective: Digital evolution represents an opportunity for ophthalmology to adapt to new care models. This study aimed to find out how the pandemic has modified the clinical practice and training activities of the ophthalmologist specialized in ocular surface, as well as to analyze emerging trends and needs. Materials and methods: This study was carried out through an online survey. A committee of 3 specialists developed a questionnaire of 25 questions structured in: 1) Participant profile; 2) Impact of the pandemic on patient management and professional activities; 3) Trends and needs. Results: Sixty-eight clinical ophthalmologists participated. There was a high degree of agreement (90%) that the pandemic has delayed ophthalmological follow-up visits and diagnosis. The participants agreed that the frequency of patients with dry eye disease (75%), stye/chalazion (62%) and blepharitis (60%) has increased. According to 28%, remote monitoring of pathologies such as dry eye, glaucoma, diabetes, conjunctivitis, hyposphagmas, styes, etc., will be common, especially in the young population. This will be especially relevant in chronic or mild pathologies of the ocular surface, and in the follow-up of patients after cataract and diabetic retinopathy interventions. Conclusions: During the pandemic, an increase in the incidence of certain ocular surface diseases has been perceived. The telematic follow-up of chronic or mild pathologies of the ocular surface entails the need to provide specific training for both the patient and the healthcare professional, in addition to screening and referral protocols that would optimize the flow of care.

New trends towards glaucoma treatment: Topical osmoprotective microemulsions loaded with latanoprost.

The chronic use of hypotensive agents eventually leads to ocular surface damage and poor patient compliance during glaucoma management. Thus, new sustained drug delivery systems are needed. This work aimed to develop osmoprotective latanoprost-loaded microemulsion formulations as new potential glaucoma treatments with ocular surface protective properties. The microemulsions were characterized and latanoprost encapsulation efficacy determined. In-vitro tolerance, osmoprotective efficacy, cell internalization as well as cell-microemulsion interactions and distribution were performed. In vivo hypotensive activity was conducted in rabbits to assess intraocular pressure reduction and relative ocular bioavailability. Physicochemical characterization showed nanodroplet sizes within 20-30 nm, being in vitro tolerance within 80 and 100% viability in corneal and conjunctival cells. Besides, microemulsions exhibited higher protection under hypertonic conditions than untreated cells. Cell fluorescence lasted for 11 days after short exposure to coumarin-loaded microemulsions (5 min) showing extensive internalization in different cell compartments by electronic microscopy. In vivo studies exhibited that a single instillation of latanoprost-loaded microemulsions reduced the intraocular pressure for several days (4-6 days without polymer and 9-13 days with polymers). Relative ocular bioavailability was 4.5 and 19 times higher than the marketed formulation. These findings suggest the use of these microemulsions as potential combined strategies for extended surface protection and glaucoma treatment.

Long-term use of antimalarial drugs in rheumatic diseases.

OBJECTIVES: To evaluate long-term use of antimalarial drugs and to analyse all causes of discontinuation. METHODS: This is a retrospective study of a cohort of rheumatic diseases patients on antimalarials, during a maximum period of 17.5 years. Case was defined as antimalarial treatment discontinuation due to: a) lack of efficacy, b) adverse events, and c) other causes. Survival techniques were used to estimate the incidence rate (IR) per 1,000 patient-years with the 95% Confidence Interval (95% CI) of antimalarial treatment discontinuation. Cox regression models were conducted to evaluate possible associated factors to antimalarial discontinuation. RESULTS: One thousand, two hundred and ninety-one medical records were reviewed, and 778 patients were included. Patients started 869 different courses of treatment, with a total follow-up of 2,263 person-years. The IR of global discontinuation was 204 (95% CI 186-224). Fifty-two per cent of the treatments stopped were related to adverse events, 14% to lack of efficacy; and 34% to other reasons (refusal to take medication, ocular comorbidity, remission, or pregnancy). Adverse events discontinuations were related to non-ophthalmologic reasons in 54.5% (gastrointestinal, neuro-psychiatric, skin problems), and to ophthalmologic adverse events in 45.5%. Nine patients suffered definite presence of antimalarial retinopathy (IR: 3.97 [IC 95%: 2.06-7.62]) and one of them irreversible loss of vision (IR: 0.44 [IC 95%: 0.06-3.12]). Women, increasing age, and chloroquine vs. hydroxychloroquine use, increased the risk of discontinuation due to ophthalmologic adverse events. CONCLUSIONS: Results suggest that antimalarials have a good balance between benefit and risk. However, we noted a number of discontinuations due to both inefficacy and adverse events. The potential for an unusual but serious ophthalmologic toxicity emphasises the importance of close ophthalmologic monitoring.

Hypochlorous acid as an antiseptic in the care of patients with suspected COVID-19 infection.

PURPOSE: The SARS-CoV-2 virus, which causes COVID-19 disease, is transmitted by aerosols or by contact with infected surfaces. The route of entry to the body is through the nasal, oral or conjunctival mucosa. Health workers must use effective protection measures against the entry of the virus into mucous membranes, both physical and antiseptic filters. There is an antiseptic used in Ophthalmology that we believe could have virucidal action against the SARS-CoV-2 virus, formulated based on 0.01% hypochlorous acid. METHODS: An exhaustive search has been carried out in the databases of Pubmed and Web of Science to identify relevant articles on the virucidal activity of hypochlorous acid in different concentrations until October 4, 2020. RESULTS: There is evidence of the virucidal efficacy of 0.01% hypochlorous acid against SARS-CoV-2. According to the different scientific publications reviewed, hypochlorous acid has virucidal efficacy against different viruses, among them, SARS-CoV-2. CONCLUSIONS: The 0.01% hypochlorous acid could act as an effective antiseptic against SARS-CoV-2, exerting a barrier on the mucosa to prevent COVID-19 infection. It can be used on the eyes, nose and mouth. We consider it necessary to assess its use in the protocol for patient health care in ophthalmology consultations, as well as to recommend its use to the general population to reduce viral load and/or prevent transmission of infection. Additional in vivo studies would be required to confirm its antiseptic action.

Association of Dry Eye with Laryngopharyngeal Reflux in Clinical Practice.

BACKGROUND: Dry eye disease (DED) is a common disorder, accounting for up to 35% of the general population. Therefore, we hypothesized that laryngopharyngeal reflux (LPR), inducing refluxate rising into airways, may involve the ocular surface and may either induce or worsen DED. AIM: To investigate the prevalence and relevance of suspected LPR in DED patients and subjects with refractive problems (RP) without DED, they were defined as non-dry eye group (NEG) in clinical practice. METHODS: This retrospective study included consecutive patients evaluated because of dry eye-like symptoms at eight tertiary ophthalmological clinics. Parameters included reflux symptom index (RSI), ocular surface disease index (OSDI), symptom assessment in dry eye (SANDE) for frequency and severity, Schirmer test, tear break-up time (BUT), and Oxford grading. RESULTS: The study included 245 subjects (72.5% females; mean age 56.3 years), 152 DED patients, and 93 sex- and age-matched NEG subjects. Pathological RSI (score>13) was detected in 80 subjects (32.6%); 68 (85%) with DED and 12 (15%) CG (OR = 8; p < .0001). In NEG, pathological RSI was associated with higher SANDE (Frequency and Severity), OSDI, and Schirmer scores (OR = 16.36; 14.51; 12.54; and 7.22, respectively. In DED patients, pathological RSI was associated with higher OSDI values (OR = 8.75). CONCLUSION: Patients with DED are at eight times higher risk for having pathological RSI than NEG patients. Moreover, pathological RSI was associated with more severe ocular symptoms both in DED and non-DED patients. The role of LPR in definite DED patients remains to be clarified, but this condition deserves to be investigated in managing patients with DED symptoms.

[Hypochlorous acid as an antiseptic in the care of patients with suspected COVID-19 infection]. / Ácido hipocloroso como antiséptico en la atención al paciente con sospecha de infección por COVID-19.

PURPOSE: The SARS-CoV-2 virus, which causes COVID-19 disease, is transmitted by aerosols or by contact with infected surfaces. The route of entry to the body is through the nasal, oral or conjunctival mucosa. Health workers must use effective protection measures against the entry of the virus into mucous membranes, both physical and antiseptic filters. There is an antiseptic used in Ophthalmology that we believe could have virucidal action against the SARS-CoV-2 virus, formulated based on 0.01% hypochlorous acid. METHODS: An exhaustive search has been carried out in the databases of Pubmed and Web of Science to identify relevant articles on the virucidal activity of hypochlorous acid in different concentrations until October 4, 2020. RESULTS: There is evidence of the virucidal efficacy of 0.01% hypochlorous acid against SARS-CoV-2. According to the different scientific publications reviewed, hypochlorous acid has virucidal efficacy against different viruses, among them, SARS-CoV-2. CONCLUSIONS: The 0.01% hypochlorous acid could act as an effective antiseptic against SARS-CoV-2, exerting a barrier on the mucosa to prevent COVID-19 infection. It can be used on the eyes, nose and mouth. We consider it necessary to assess its use in the protocol for patient health care in ophthalmology consultations, as well as to recommend its use to the general population to reduce viral load and / or prevent transmission of infection. Additional in vivo studies would be required to confirm its antiseptic action.

Development of an osmoprotective microemulsion as a therapeutic platform for ocular surface protection.

Self-emulsified osmoprotective ophthalmic microemulsions (O/A) were prepared by combining betaine/leucine, clusterin/oleanolic acid, and hyaluronic acid or Dextran. The microemulsions contained an internal oily phase (1.2%), an external aqueous phase (96.3%), cosolvents (1%), and surfactants (1.5%). Physicochemical characterization and in vivo and in vitro tolerance were analyzed. The formulations' osmoprotective in vitro activity was assayed in a hyperosmolar model in human corneal cells. Average internal phase sizes were 16-26 nm for the microemulsions including Dextran. Addition of hyaluronic acid increased the size range (25-39 nm). Addition of osmoprotectants did not change nanodroplet size. The formulations were isotonic (280-290 mOsm/L) with neutral pH (≈7) and zeta potential (-10 to 0 mV), low surface tension (≈35-40mN·m-1), and low viscosity (≈1 mPa·s), except for the microemulsions containing hyaluronic acid (≈4-5 mPa·s). SEM and cryo-TEM showed that all formulations exhibited sphere-shaped morphology with good cell tolerance (≈100%) and were stable at 8 °C for 9 months. Osmoprotective formulations were well tolerated in vitro and in vivo, protecting cells from hypertonic stress. We therefore developed stable microemulsions compatible with the ocular surface that could constitute a novel tool for treatment of ophthalmic diseases.

Aniridia and the ocular surface: Medical and surgical problems and solutions.

Congenital aniridia is a multisystemic genetic disease due to a mutation in PAX6 gene which severely affects the development and functionality of the human eyes. In patients affected by the mutation, aside from the absence or defects of iris tissue formation, abnormalities in position or opacities of the crystalline lens, macular hypoplasia, ocular surface disease is the main cause of visual loss and the deterioration of the quality of life of most patients. Limbal stem cell deficiency combined with tear film instability and secondary dry eye cause aniridic keratopathy which, in advanced stages, ends up in corneal opacification. In this paper, the actual knowledge about congenital aniridia keratopathy physiopathology and medical and surgical treatment options and their efficacy are discussed. Indications and results of topical treatments with artificial tears and blood-derivatives in its initial stages, and different surgical techniques as limbal stem cell transplantation, keratoplasty and keratoprostheses are reviewed. Finally, recent advances and results in regenerative medicine techniques with ex vivo stem cell cultivation or other types of cultivated cells are presented.

Role of metalloproteases in retinal degeneration induced by violet and blue light.

INTRODUCTION: An essential role for metalloproteases (MMPs) has been described in blood vessel neoformation and the removal of cell debris. MMPs also play a key role in degenerative processes and in tumors. The participation of these enzymes in light-induced phototoxic processes is supported by both experimental and clinical data. Given that patients with age-related macular degeneration often show deposits, or drusen, these deposits could be the consequence of deficient MMP production by the pigment epithelium. OBJECTIVE: To gain insight into the regulation of metalloproteases in the pathogenia of retinal degeneration induced by light. MATERIALS AND METHODS: We examined the eyes of experimental rabbits exposed for 2 years to circadian cycles of white light, blue light and white light lacking short wavelengths. For the trial the animals had been implanted with a transparent intraocular lens (IOL) and a yellow AcrySof((R)) IOL, one in each eye. After sacrificing the animals, the retinal layer was dissected from the eye and processed for gene expression analyses in which we examined the behavior of MMP-2, MMP-3 and MMP-9. RESULTS: MMP-2 expression was unaffected by the light received and type of IOL. However, animals exposed to white light devoid of short wavelengths or those fitted with a yellow IOL showed 2.9- and 3.6-fold increases in MMP-3 expression, respectively compared to controls. MMP-9 expression levels were also 3.1 times higher following exposure to blue light and 4.6 times higher following exposure to white light lacking short wavelengths or 4.2 times higher in eyes implanted with a yellow IOL. CONCLUSION: Exposure to long periods of light irrespective of its characteristics leads to the increased expression of some MMPs. This alteration could indicate damage to the extracellular matrix and have detrimental effects on the retina.

Changes in Left Ventricular Mechanics After Sleeve Gastrectomy.

OBJECTIVE: The aim of this study was to examine echocardiographic parameters of left ventricle (LV) mechanics in obese patients before and after sleeve gastrectomy (SG). DESIGN AND METHODS: Twenty-five obese individuals submitted to laparoscopic SG were enrolled in this study. Echocardiography was performed before and after the procedure, and left ventricle mechanics were evaluated by speckle tracking imaging. RESULTS: Before surgery, altered global longitudinal strain (GLS) values were present in 56% of the patients. In a mean follow-up of 3.6 ± 0.5 months after surgery, there was an increase in GLS values (from 17.4 ± 3.2 to 19.3 ± 2.7%, P = 0.01). There was an inverse correlation between the absolute values of GLS in the preoperative period and the variation in the GLS at follow-up (r = 0.577, P = 0.002). Measurements of global circumferential strain (GCS), global radial strain (GRS), and LV twist were normal preoperatively and did not change after surgery. CONCLUSIONS: Altered global longitudinal strain values were common in young obese patients. Sleeve gastrectomy increased global longitudinal strain even in the early postoperative phase without promoting changes in global radial strain, global circumferential strain, and left ventricle twist measurements.

Dry eye disease treatment: the role of tear substitutes, their future, and an updated classification.

OBJECTIVE: The aim of this review is to summarize the results of a consensus meeting held by a group of experts in dry eye disease (DED) to discuss the importance of tear substitutes in the treatment of DED. The meeting focused especially on the main characteristics of lacrimal substitutes, the development of in vitro models to investigate DED pathophysiology and treatment, the importance of conducting rigorous clinical trials, the requirements of the upcoming European Legislation on medical devices, the advances in the formulation of safer preservatives, the peculiarities of treatment in younger subjects, and the importance of an updated terminology for lacrimal substitutes. MATERIALS AND METHODS: A literature search was conducted using MEDLINE, with different combinations of pertinent keywords, depending on the subject under discussion, such as "dry eye disease"; "tear substitutes"; "in vitro models"; "ocular surface"; "clinical trials"; "European Regulation"; "preservatives" "younger patients". Also, each author included in the discussion selected articles from their personal library. Using a consensus-based method called nominal group technique to reach a conclusion and proposal for a new classification of eye drops used to improve the tear film and ocular surface epithelia, the experts also conducted a round table meeting. RESULTS: The new terms proposed by the authors are "wetting agents", "multiple-action tear substitutes" or "ocular surface modulators". The new classification is needed to distinguish eye drops used to improve the tear film and ocular surface epithelia, in line with the new definition of DED, which recognizes the loss of ocular homeostasis, and the creation of a vicious circle of chronic inflammation and ocular damage as fundamental aspects of DED pathophysiology. CONCLUSIONS: Although tear substitutes have been historically used to provide eye lubrication to the ocular surface, recent advances in the pathophysiology of dry eye disease (DED) clarified that treatment should not just focus on tear film quality or quantity, but address the loss of homeostasis of the ocular surface, blocking the vicious circle of chronic inflammation and ocular damage. Given the scant comparative evidence on tear substitutes currently on the market, further studies should focus on developing new agents, considering the advantages provided by in vitro models, importance of conducting rigorous clinical trials, availability of less harmful preservatives and obligations related to the new European legislation on medical devices. Based on the discussion of these topics, a group of experts held a consensus meeting to identify new and more appropriate terms for different tear substitutes. The proposed terms are wetting agents, multiple-action tear substitutes and ocular surface modulators. Regardless of the agent used, it is important to note that tear substitutes represent one of many options for DED treatment, which should not overlook the psychological aspects of the disease and the peculiarities of younger subjects, who seem to have a higher risk for DED, possibly related to digital devices excessive use.

Management of corneal neurotrophic ulcers with Cacicol®-RGTA (ReGeneraTing Agent): a case series. / Manejo de las úlceras corneales neurotróficas con Cacicol®- ReGeneraTing Agent: serie de casos.

PURPOSE: Neurotrophic corneal ulcers are difficult to treat, and the conventional treatment often results in failure. A new matrix regenerating agent ("ReGeneraTing Agents"), Cacicol® (Laboratoires Théa), has demonstrated good results over the last few years. Therefore, the aim of this study was to evaluate the response to Cacicol® in a series of cases with neurotrophic corneal ulcers. METHODS: Retrospective case series looking at 11 patients with corneal ulcers unresponsive to conventional therapy that underwent treatment with Cacicol®. One cycle included 1 drop every two days for 5 days. RESULTS: The range of conventional therapy prior to Cacicol® was 0-91 days. On introducing Cacicol® 82% (9/11) of the cases were cured, and 18% (2/11) failed, requiring an amniotic membrane transplant or penetrating keratoplasty. The healing only required one cycle of Cacicol® in 67% (6/9) of the patients. More than one cycle of Cacicol® was needed in 45% (5/11) patients. One corneal bacterial ulcer responded favourably and one case related to Acanthamoeba did not respond. Most of the patients improved or maintained their visual acuity. CONCLUSION: Cacicol® was a useful therapy in a high number of difficult neurotrophic corneal ulcers, including corneal infections. Some cases may require more than one cycle of Cacicol® or used as first-line treatment in order to achieve the desired result.

Effects and safety of perfluorohexyloctane on the eye surface and corneal endothelium. / Efectos y seguridad del perfluorohexiloctano en la superficie ocular y el endotelio corneal.

OBJECTIVE: To evaluate the effects and safety of topical drops of perfluorohexyloctane (F6H8) on the ocular surface and the corneal endothelium. METHODS: Forty-five patients (90 eyes) diagnosed with dry eye disease were recruited and prescribed treatment with F6H8 as part of a six-month prospective multicentre study. Variables in corneal staining were documented using the National Eye Institute/Industry Workshop scale. The conjunctival variables included using the Oxford scale, as well as corneal parameters, such as central corneal thickness, cell density, coefficient of variation, hexagonality, and mean cell area, at the start of the study, and at 3months and 6months. Compliance and satisfaction with the treatment were measured. RESULTS: F6H8 drops reduced mean corneal staining based on the NEI scale in compliant patients to a mean of -0.84 ± 1.95 at 3months (P=.001) and to -1.65 ± 2.42 at 6months (P<.001). Conjunctival staining at 6months showed a mean decrease of -0.13 (P=.319). The endothelial parameters did not show a significant difference, in contrast to the central corneal thickness that showed a statistically significant decrease (545.30 ± 32.25 at the start of the study to 538.40 ± 31.36 after 6months, P=.009). At the end of the study, 46% of patients reported feeling subjectively better, 40.5% felt the same, and 13.5% felt subjectively worse. CONCLUSIONS: Topical treatment with F6H8 for dried eye disease did not alter the measured variables of the corneal endothelium, but showed improvement in corneal staining and satisfaction.