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Resumen La aniridia congenita es una patologia multisistemica derivada de una mutacion en el gen PAX6 que afecta severamente al desarrollo y a la funcion de los globos oculares. En los pacientes afectados por esta enfermedad, ademas de la ausencia o defectos en la formacion del iris, anomalias y opacidades del cristalino e hipoplasia de la macula, la patologia de la superficie ocular es la responsable del deterioro visual y de la calidad de vida en un porcentaje muy importante de casos. La insuficiencia limbica producida por la enfermedad, junto con la inestabilidad y el deterioro de la pelicula lagrimal desarrollan la llamada queratopatia que, en estadios avanzados, conlleva la opacificacion final de la cornea. En este articulo se repasan los conocimientos actuales tanto de la fisiopatologia de la queratopatia como de los posibles tratamientos medicos y quirurgicos disponibles en el presente y las evidencias existentes al respecto de su eficacia en esta patologia ocular. Se describen las indicaciones y los resultados de los tratamientos topicos con lagrimas artificiales y colirios hemoderivados en las fases iniciales, y de las diferentes tecnicas quirurgicas como los trasplantes alogenicos de limbo corneal, las queratoplastias, las queratoprotesis y, finalmente, se expondran los avances y resultados actuales de la medicina regenerativa basada en el trasplante de celulas obtenidas, expandidas y modificadas ex vivo en el laboratorio.

Allergic conjunctivitis is a disease of increasing prevalence that affects both children and adults and causes significant deterioration of their quality of life and sometimes irreversible visual damage. There are various forms of the disease, some are allergen-induced such as seasonal and perennial allergic conjunctivitis, giant papillary conjunctivitis, and contact allergic blepharoconjunctivitis, whereas others are not always explained by allergen exposure, such as vernal keratoconjunctivitis and atopic keratoconjunctivitis. We review their clinical course, characteristics, and differential diagnosis, and highlight recent advances in their pathophysiology and treatment.

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 (DED) 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 (NEI) 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 three months and six months. 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 three months (P = .001) and to −1.65 ± 2.42 at six months (P Conclusions Topical treatment with F6H8 for DED did not alter the measured variables of the corneal endothelium, but showed improvement in corneal staining and satisfaction.

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.

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 apoptoticinduced cell death. All osmoprotectants modified RCS, and polymers increased their value over 100%. LCarnitine 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).

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 &gt, 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.

The ocular surface flora perform an important role in the defense mechanisms of the ocular surface system. Its regulation of the immunological activity and the barrier effect against pathogen invasion are remarkable. Composition of the flora differs according to the methods of investigation, because the microbiome, composed of the genetic material of bacteria, fungi, viruses, protozoa, and eukaryotes on the ocular surface, differs from the microbiota, which are the community of microorganisms that colonize the ocular surface. The observed composition of the ocular surface flora depends on harvesting and examining methods, whether with traditional culture or with more refined genetic analysis based on rRNA and DNA sequencing. Environment, diet, sex, and age influence the microbial flora composition, thus complicating the analysis of the baseline status. Moreover, potentially pathogenic organisms can affect its composition, as do various disorders, including chronic inflammation, and therapies applied to the ocular surface. A better understanding of the composition and function of microbial communities at the ocular surface could bring new insights and clarify the epidemiology and pathology of ocular surface dynamics in health and disease. The purpose of this review is to provide an up-to-date overview of knowledge about this topic.

The seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was examined among 105 healthcare workers (HCWs) exposed to four patients who were laboratory confirmed with coronavirus disease 2019 (COVID-19), the disease caused by SARS-CoV-2 infection. These HCWs were immediately under quarantine for 14 days as soon as they were identified as close contacts. The nasopharyngeal swab samples were collected on the first and 14th day of the quarantine, while the serum samples were obtained on the 14th day of the quarantine. With the assay of enzyme immunoassay (EIA) and microneutralization assay, 17.14% (18/105) of HCWs were seropositive, while their swab samples were found to be SARS-CoV-2 RNA negative. Risk analysis revealed that wearing face mask could reduce the infection risk (odds ratio [OR], 0.127, 95% confidence interval [CI] 0.017, 0.968), while when exposed to COVID-19 patients, doctors might have higher risk of seroconversion (OR, 346.837, 95% CI 8.924, 13479.434), compared with HCWs exposed to colleagues as well as nurses and general service assistants who exposed to patients. Our study revealed that the serological testing is useful for the identification of asymptomatic or subclinical infection of SARS-CoV-2 among close contacts with COVID-19 patients.

Purpose The purpose of this study was to evaluate the frequency and clinical presentation of conjunctivitis in hospitalized patients with COVID-19. Methods A cross-sectional study was conducted at the Hospital Clinico San Carlos of Madrid, Spain. A total of 301 subjects from the COVID admission unit with laboratory-confirmed SARS-CoV-2 infection were included. The presence and clinical characteristics of conjunctivitis were evaluated. Laboratory, radiological, and clinical results in patients with and without conjunctivitis stratified by sex were analyzed. Results Of the 301 subjects included, 180 patients (59.8%) were male and the median age was 72 years (IQ 59–82). Overall, 35 patients (11.6%) were diagnosed with acute conjunctivitis. We found no relationship between the COVID-19 severity score and the presence of conjunctivitis (P = 0.17). However, conjunctivitis was more frequent in males with moderate clinical severity and in women classified as clinically mild. The natural history of the disease seems to be a rapid self-limited conjunctivitis that improves without treatment and does not affect visual acuity nor associate short-term complications. Conclusions Approximately, 1 out of 10 hospitalized non-critical COVID-19 patients presents conjunctivitis during the disease. Compared with other viral conjunctivitis, we found distinctive clinical findings that could guide defining and differentiating conjunctivitis in COVID-19 patients. Trial registration number 20/336_E_COVID

Corneal nerves are key components of the physiological system that controls ocular surface homeostasis. The cornea is primarily innervated by the ophthalmic branch of the trigeminal nerves (cranial nerve V), which distend bilaterally from the pons. The nasociliary branch (afferent) of the ophthalmic nerve is sensory for cornea, eyelid and conjunctiva. These nerve fibres play a role in sensing temperature, chemical and mechanical stimuli, and pain, whereas, branches of the facial nerve (cranial nerve VII) contain motor nerves that control blinking and autonomic (sympathetic and a paucity of parasympathetic) fibres that stimulate tear production and secretion via feedback loops between the ocular surface, lacrimal glands and brain. Disruption of these nerves with interruption of neural feedback loops between the ocular surface and lacrimal glands can lead to corneal diseases such as dry eye disease (DED) and neurotrophic keratopathy (NK). Inversely, hypersensitivity of the nerve fibres and/or dysregulation of pain-controlling nervous centres may lead to neuropathic pain. Recently, medications that specifically target regeneration of corneal nerves have started to become available - and considering the high prevalence of diseases associated with corneal nerve dysfunction, these agents promise to fulfil a hitherto important unmet need. In this review, we explore the physiology of corneal nerves, the pathology of corneal nerve diseases and how these relate to neuropathic pain, NK and DED. We also discuss what novel treatments may be useful against diseases involving corneal nerves.

Neurotrophic Keratopathy (NK) refers to a condition where corneal epitheliopathy leading to frank epithelial defect with or without stromal ulceration (melting) is associated with reduced or absent corneal sensations. Sensory nerves serve nociceptor and trophic functions, which can be affected independently or simultaneously. Loss of trophic function and consequent epithelial breakdown exposes the stroma making it susceptible to enzymatic degradation. Nerve pathology can range from attrition to aberrant re-generation with corresponding symptoms from anaesthesia to hyperaesthesia/allodynia. Many systemic and ocular conditions, including surgery and preserved medications can lead to NK. NK can be mild (epithelium and tear film changes), moderate (non-healing epithelial defect) or severe (stromal melting and perforation). Moderate and severe NK can profoundly affect vision and adversely impact on the quality of life. Medical management with lubricating agents from artificial tears to serum/plasma drops, anti-inflammatory agents, antibiotics and anti-proteases all provide non-specific relief, which may be temporary. Contact lenses, punctal plugs, lid closure with botulinum toxin and surgical interventions like tarsorrhaphy, conjunctival flaps and amniotic membrane provide greater success but often at the cost of obscuring sight. Corneal surgery in a dry ocular surface with reduced sensation is at high risk of failure. The recent advent of biologicals such as biopolymers mimicking heparan sulfate; coenzyme Q10 and antisense oligonucleotide that suppress connexin 43 expression, all offer promise. Recombinant nerve growth factor (cenegermin), recently approved for human use targets the nerve pathology and has the potential of addressing the underlying deficit and becoming a specific therapy for NK.

To describe and analyze the biomicroscopic features and in vivo confocal microscopy of the crystalline form of pre-Descemet corneal dystrophy (PDCD). We examined two non-related families using biomicroscopy, in vivo confocal microscopy, and a genetic study using a gene panel test, looking for mutations in the PIKFYVE gene. A slit-lamp examination of the first family revealed polychromatic crystalline punctiform opacities distributed all over the stroma in 8 of 11 family members in three generations with an autosomal dominant inheritance. The second family showed in three of four members in two generations the same opacities located in the pre-Descemet region. It was also a hint for autosomal dominant inheritance. The in vivo confocal microscopy identified numerous rounded and hyperreflective stromal particles measuring 10–15 μm in diameter, with the highest density in the posterior stroma and with normal keratocytes. No systemic disease was diagnosed. No variants or mutations were identified in PIKFYVE gene. Polychromatic deposits in patients with Punctiform and Polychromatic Pre-Descemet corneal dystrophy can be located not only in the deep stroma but also in the anterior and middle stroma. Our presentation reveals the possibility of considering this characteristic corneal disorder as a corneal dystrophy of its own and not as a subtype of pre-Descemet corneal dystrophy.

Summary Introduction To determine outcomes of conjunctival autograft attached with fibrin glue (FG) for primary pterygium , and compare these outcomes in expert versus closely supervised trainee ophthalmologists. Methods This was a retrospective, comparative, non-randomized, interventional study. Patients were recruited among those with primary nasal pterygium undergoing FG conjunctival autograft. Surgery was performed by expert (136 eyes) or closely supervised trainee (128 eyes) ophthalmologists. Mean follow-up was 7.82 ± 8.23 months. Main outcome measures were recurrence rate, reoperation rate and complications. Results The study sample comprised 264 eyes of 225 patients. Participants were of mean age 47.09 ± 12.89 years; 46.7% were male, 28.4% Caucasian and 70.5% Hispanic. Recurrence was recorded in 6.4%: 5.9% in the expert group and 7% in the trainee group (P = 0.704) and reoperation in 1.9%: 0.7% and 3.1% (P = 0.202), respectively. Both groups showed similar rates of complications such as transient graft edema, graft dehiscence, hematoma or ocular hypertension . Reoperation was slightly more frequent in patients younger than 40 years (P = 0.064). Conclusions Good outcomes were observed for FG conjunctival autografting in primary pterygium surgery, with no differences recorded between supervised trainee and expert surgeons. Our findings suggest the need to supervise pterygium surgeries during training.

PURPOSE To report 2 cases of cornea verticillata (CV) after vandetanib treatment for medullary thyroid carcinoma (MTC). METHODS In this retrospective interventional, case-report study, 2 patients who under vandetanib treatment for MTC were referred to our ophthalmology department because of vision complaints. Both subjects underwent a complete ophthalmologic examination, including confocal microscopy (CM) using the Heidelberg Retina Tomograph and Rostock Cornea Module. RESULTS A 70-year-old man and a 43-year-old woman, both with a history of MTC under treatment with vandetanib for 5 months and 30 months, respectively, presented with blurred vision. In both patients, a mild CV pattern was observed although deposits were more evident in the male patient. CM images showed hyperreflective deposits in the corneal epithelium and subepithelial nerve plexus. Bright microdots were also seen throughout the stroma, along with a few hyperreflective keratocytes in the anterior stroma. CONCLUSIONS In both patients, vandetanib seemed to be the cause of CV. The CM images supported the idea of drug-lipid complex deposits in vandetanib-induced CV.

Resumen Objetivo Estudio epidemiologico, observacional, no intervencionista, cuya finalidad es determinar las caracteristicas clinicas y la frecuencia de la conjuntivitis adenovirica diagnosticada con AdenoPlus ® en pacientes que presentaban signos y sintomas de conjuntivitis aguda, asi como establecer la seguridad de dicho test. Metodo Este trabajo presenta los datos recogidos de los 386 pacientes incluidos en Espana. Los pacientes debian presentar signos o sintomas de conjuntivitis aguda de ≤ 7 dias de evolucion. La edad minima para participar era de 1 ano. Se excluyeron los pacientes ya tratados con diversos farmacos (antiviricos topicos, esteroides topicos o inmunomoduladores). Se utilizo un cuestionario estandarizado para recoger los datos del paciente y los resultados del test. Resultados Veintidos centros reclutaron 386 pacientes, de los cuales 329 fueron analizados. El porcentaje de «AdenoPlus ® positivo» fue del 36,2% (119/329). En el 84,1% de casos los investigadores consideraron que la conjuntivitis era de origen virico, pero solo el 50,3% de ellos vio su criterio clinico confirmado por el test. Los pacientes con resultado positivo a adenovirus tendian a presentar mas signos y sintomas comparados con el resto de pacientes. Conclusiones Ningun signo ni sintoma puede considerarse patognomonico de la enfermedad, dificultando el diagnostico por parte del clinico. El test AdenoPlus ® es una prueba de inmunoanalisis rapida para la deteccion de adenovirus directamente de secrecion lagrimal, y puede ser una herramienta util para ayudar en el diagnostico diferencial precoz en pacientes con signos y sintomas de conjuntivitis con una evolucion de 7 dias o menos.

Objective Non-interventional, observational, epidemiology study to assess clinical characteristics and frequency of adenovirus conjunctivitis diagnosed by AdenoPlus® in patients who presented with signs and symptoms of acute conjunctivitis. Safety aspects during use of the test were analyzed as well. Method This analysis presents the data obtained from the 386 patients enrolled in Spain. Patients had to present with acute signs and symptoms of conjunctivitis ≤7 days. The minimum age was 1 year old. Patients who had already used local antiviral therapies, topical steroids or immuno-modulators were not allowed to enter the study. A standardized questionnaire was used to collect patient's ocular history and test results. Results A total of 386 patients were recruited in 22 sites, being analyzed 329 patients. Among them, the percentage of “AdenoPlus® positive” was 36.2% (119/329). Before the test was performed, in 84.1% of the cases, investigators believed that the conjunctivitis was of viral origin but only 50.3% of the investigators had their clinical assessment confirmed by the test. Patients who tested positive for adenoviral conjunctivitis presented higher percentages of signs and symptoms than the rest of the patients. Conclusions None of the signs or symptoms could be qualified as pathognomonic of the disease, being difficult for the clinicians to perform an accurate diagnosis. AdenoPlus® test is an antigen based immunoassay test that detects the presence of adenovirus directly from tears, and it can be an useful tool to help early differential diagnosis in patients with conjunctivitis signs and symptoms lasting for less than or equal to 7 days.

Purpose: To determine variations in cytokine levels of glaucoma patients treated either with preservative-free latanoprost or preserved latanoprost, relative to healthy individuals. Methods: Tear samples were collected from 39 healthy subjects, 20 glaucoma patients treated with preserved latanoprost, and 20 patients treated with preservative-free latanoprost. A set of 27 inflammatory cytokines was analyzed in each group, including interleukin (IL)-1β, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL9, IL-10, IL-12 (p70), IL-13, IL-15, IL-17, eotaxin, fibroblast growth factor (FGF) basic, granulocyte colony stimulating factor (G-CSF), granulocyte monocyte colony stimulating factor (GM-CSF), interferon (IFN)-γ, interferon gamma-induced protein (IP)-10, monocyte chemo attractant protein (MCP)-1MCAF, macrophage inflammatory protein (MIP)-1α, MIP-1β, platelet-derived growth factor (PDGF)-BB, regulated on activation, normal T cell expressed and secreted (RANTES), tumor necrosis factor (TNF)-α and vascular endothelial growth factor (VEGF). Cytokine concentrations were obtained by the Bio-Plex Human Cytokine Immunoassay. Non-invasive tear breakup time (NI-TBUT), tear meniscus height, corneal fluorescein staining, conjunctival hyperemia and ocular surface disease index (OSDI) were assessed in patients treated with preservative-free and preserved latanoprost. Results: The levels of IL-2, IL-5, IL-10, IL-12 (p70), IL-13, IL-15, IL-17, FGF basic, PDGF-BB, and TNF-α were significantly higher in patients receiving preserved latanoprost, compared to normal controls (p < 0.05). The expression of all the cytokines studied remained statistically invariable in patients receiving preservative-free latanoprost, compared to healthy subjects (p > 0.05). Ocular surface parameters were not significantly different in both glaucoma groups, and no correlation between these clinical parameters and cytokine levels was observed. Conclusions: Treatment with preserved latanoprost has a direct impact on tear cytokine levels, whereas this effect is not observed upon preservative-free latanoprost instillation.

The members of the Management and Therapy Subcommittee undertook an evidence-based review of current dry eye therapies and management options. Management options reviewed in detail included treatments for tear insufficiency and lid abnormalities, as well as anti-inflammatory medications, surgical approaches, dietary modifications, environmental considerations and complementary therapies. Following this extensive review it became clear that many of the treatments available for the management of dry eye disease lack the necessary Level 1 evidence to support their recommendation, often due to a lack of appropriate masking, randomization or controls and in some cases due to issues with selection bias or inadequate sample size. Reflecting on all available evidence, a staged management algorithm was derived that presents a step-wise approach to implementing the various management and therapeutic options according to disease severity. While this exercise indicated that differentiating between aqueous-deficient and evaporative dry eye disease was critical in selecting the most appropriate management strategy, it also highlighted challenges, based on the limited evidence currently available, in predicting relative benefits of specific management options, in managing the two dry eye disease subtypes. Further evidence is required to support the introduction, and continued use, of many of the treatment options currently available to manage dry eye disease, as well as to inform appropriate treatment starting points and understand treatment specificity in relation to dry eye disease subtype.

Objetivo Evaluar los efectos y la seguridad del perfluorohexiloctano (F6H8) tópico en la superficie ocular y el endotelio corneal. Métodos Fueron diagnosticados 45 pacientes (90 ojos) de enfermedad de ojo seco, se seleccionaron y se les prescribió tratamiento con F6H8 durante 6 meses. Las variables en la tinción corneal se documentaron usando la escala National Eye Institute/Industry Workshop (NEI), las variables conjuntivales usando la escala Oxford y los parámetros corneales, como el espesor corneal central, la densidad celular, el coeficiente de variación, la hexagonalidad y el área celular promedio, al inicio del estudio, a los 3 meses y a los 6 meses. Se evaluó también el cumplimiento y la satisfacción. Resultados El tratamiento con F6H8 redujo la tinción corneal promedio en pacientes cumplidores a una media de -0, 84 ± 1, 95 a los 3 meses (p = 0, 001) y a -1, 65 ± 2, 42 a los 6 meses (p < 0, 001). La tinción conjuntival a los 6 meses mostró una disminución promedio de -0, 13 (p = 0, 319). Los parámetros endoteliales no mostraron diferencia significativa, excepto el espesor corneal central, que mostró una disminución estadísticamente significativa (era de 545, 30 ± 32, 25 µm al comienzo del estudio y 538, 40 ± 31, 36 µm tras 6 meses, p = 0, 009). Al final del estudio, el 46% de los pacientes informaron sentirse subjetivamente mejor, el 40, 5% no sintió cambios y el 13, 5% se sintió subjetivamente peor. Conclusiones El tratamiento tópico con F6H8 para la enfermedad de ojo seco no alteró las variables medidas del endotelio corneal, aunque sí mostró mejoría en la tinción corneal y en la satisfacción. 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 3 months and 6 months. 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 3 months (P=.001) and to -1.65 ± 2.42 at 6 months (P

Pasquale Aragona,1 Jose M Benítez-del-Castillo,2 Minas T Coroneo,3 Subhanjan Mukherji,4 Jacqueline Tan,5 Evelien Vandewalle,6 Algis Vingrys,7 Haixia Liu,8 Cindy Carlisle-Wilcox,8 Joseph Vehige,8 Peter A Simmons5,8 1Department of Biomedical Sciences, Università di Messina, Messina, Italy; 2Department of Ophthalmology, Hospital Clinico de Madrid, Universidad Complutense, Madrid, Spain; 3M.T. Coroneo Pty. Ltd, Randwick, NSW, Australia; 4Department of Ophthalmology, James Paget University Hospital, Great Yarmouth, UK; 5Optometry and Vision Science, UNSW Sydney, Sydney, NSW, Australia; 6Department of Ophthalmology, University Hospitals Leuven, Leuven, Belgium; 7University of Melbourne EyeCare Clinic, Carlton, VIC, Australia; 8Allergan, an AbbVie company, Irvine, CA, USACorrespondence: Peter A SimmonsPCS Research, 16611 Camille Place, Yorba Linda, CA, USATel + 1-714-743-3352Email pasimmons17@gmail.comPurpose: To compare the efficacy and safety of an artificial tear combining the polymers carboxymethylcellulose (CMC) and hyaluronic acid (HA), to a formulation of CMC alone in subjects with dry eye.Methods: A preservative-free artificial tear (CMC-HA) was compared with an existing artificial tear (CMC). Subjects with mild-to-severe signs and symptoms of dry eye were enrolled in this double-masked, randomized, multicenter trial, and dosed at least twice daily for 90 days, with follow-up visits at Days 7, 30, 60, and 90. Ocular Surface Disease Index (OSDI) was the primary outcome measure. Secondary outcome measures were tear break-up time (TBUT), ocular surface staining, Schirmer test with anesthesia, and visual analog scale (VAS) scores of dry eye symptom severity and formulation acceptability. Safety measures included adverse events, biomicroscopy, and visual acuity.Results: A total of 460 subjects were enrolled across 45 sites (38 in Europe; 7 in Australia), of whom 454 were randomized to receive treatment. The per-protocol (PP) population consisted of 394 subjects, 364 (92.4%) of whom completed the study. In the PP population, the mean ± SD change from baseline in OSDI score at the primary timepoint, Day 90, was − 16.9± 17.5 for CMC-HA and − 16.0± 16.1 for CMC. CMC-HA was non-inferior to CMC based upon a confidence interval method. Both treatments significantly improved (P< 0.001) OSDI, symptom VAS scores, TBUT, and ocular surface staining from baseline at all follow-up visits, with minimal differences between groups. Greater reduction of overall ocular pain/discomfort was reported in subjects using CMC-HA versus CMC (P=0.048). Approximately 10% of subjects in each group reported treatment-related adverse events of generally mild to moderate severity.Conclusion: The new CMC-HA formulation was effective and well tolerated, and demonstrates a greater potential for symptom relief compared with CMC. These data support implementation of this formula for the management of dry eye patients.Keywords: carboxymethylcellulose, hyaluronic acid, artificial tears, dry eye

Purpose To assess intraobserver repeatability and interobserver and intersession reproducibility of lower tear meniscus height (LTMH) measurements obtained using a new anterior segment swept-source optical coherence tomography (SS-OCT) device. Agreement with Fourier-domain (FD) OCT (Spectralis) was also examined. Methods In an observational cross-sectional study, one eye of 29 healthy subjects was randomly imaged with both devices at our center. Two examiners then randomly measured the LTMH using the software's calipers. To assess intraobserver repeatability and interobserver and intersession reproducibility, within-subject standard deviation (Sw), test-retest repeatability, coefficients of variation (CoV), and intraclass correlation coefficients (ICCs) were calculated. Agreement between both devices was also determined in Bland-Altman plots. Results Mean LTMHs for SS-OCT and FD-OCT were 276.6 ± 87.6 and 280.3 ± 80 μm, respectively. Using the SS-OCT device, intraobserver CoV, interobserver CoV, and intersession CoV were found to be ≥16.9%, ≤7.2%, and ≤11.5%, respectively. ICCs for these parameters were ≤88%, ≥97%, and ≥94%, respectively. Bland-Altman analysis indicated poor agreement between SS-OCT and FD-OCT, and the correlation was low (CoV 34.5%, ICC 0.36). Conclusions SS-OCT LTMH measurements showed excellent interobserver and intersession repeatability along with good intraobserver reproducibility. Agreement between the devices was poor.

Dry eye is commonly treated with artificial tears; however, developing artificial tears similar to natural tears is difficult due to the complex nature of tears. We characterized and evaluated a novel artificial tear formulation with components similar to the lipid and aqueous constituents of natural tears. Nano-liposomes, composed in part of phosphatidylcholine, were dispersed in an aqueous solution of bioadhesive sodium hyaluronate. Liposome size, zeta potential, and physicochemical properties of the fresh and stored (4°C) liposomal formulation were analyzed. In vitro tolerance was tested using human corneal and conjunctival cell lines by exposures of 15 min to 4 h. The tolerance of the liposomal formulation was evaluated in animals (rabbits). The average liposome size was 186.3 +/- 7.0 nm, and the zeta potential was negative. The osmolarity of the formulation was 198.6 +/- 1.7 mOsm, with a surface tension of 36.5 +/- 0.4 mN/m and viscosity of 3.05 +/- 0.02 mPa·s. Viability values in the human corneal and conjunctival cell lines were always >80%, even after liposomal formulation storage for 8 weeks. Discomfort and clinical signs after instillation in rabbit eyes were absent. The new formulation, based on phosphatidylcholine-liposomes dispersed in sodium hyaluronate has suitable components and characteristics, including high in vitro cell viability and good in vivo tolerance, to serve as a tear substitute.

Resumen Caso clinico Mujer de 22 anos que consulto por cefalea y disminucion de la vision. Presentaba papiledema asimetrico y, en las pruebas de imagen, un descenso amigdalar de 6 mm, siendo diagnosticada de hipertension intracraneal idiopatica coincidente con una malformacion de Chiari (MC). Discusion La MC tipo I es la mas frecuente de este grupo de malformaciones y se caracteriza por un descenso amigdalar superior a 5 mm, pudiendo originar hipertension intracraneal por el bloqueo del liquido cefalorraquideo. En este caso la MC no fue la responsable de la hipertension intracraneal, sino una casualidad al coincidir ambos procesos.

Case report The case involves a 22-year-old woman who presented with headache and decreased vision. She showed asymmetric papilledema, and a 6-mm tonsillar descent was observed in the image tests. She was diagnosed with secondary intracranial hypertension coinciding with the symptoms of a Chiari malformation (MC). Discussion Chiari malformation type I is the most common in this group of malformations, and is characterized by a greater than 5 mm descent of the tonsils, being able to cause increased intracranial pressure and papilledema by blocking the flow of the cerebrospinal fluid. In this case, the MC was not the responsible for triggering the secondary intracranial hypertension, but a mere coincidence of both processes.

Purpose Artificial tears are widely used in the treatment of dry eye disease, although current formulations do not closely resemble natural tears. The purpose of this study was the design and characterization of a novel in situ gelling artificial tear formulation, containing both lipid and aqueous components, in order to resemble natural tears and replenish the tear film. Methods Liposomes, containing phosphatidylcholine, cholesterol, vitamins A and E, were prepared by the thin-film hydration method. The aqueous phase of the formulation was comprised of gellan gum, hydroxypropyl methylcellulose, levocarnitine, electrolytes (sodium chloride and potassium chloride), trehalose, and borates. The artificial tear was characterized in terms of liposome size, pH, surface tension, and viscosity. In vitro tolerance studies were performed in a human epithelial carcinoma cell line (HeLa) and a murine macrophage cell line (J774). In vivo tolerance was assessed in rabbits. Results Liposomes presented a unimodal distribution with a mean size of 200.1 ± 4.4 nm. The resulting surface tension was 53.4 ± 1.1 mN/m (at 33 °C) and the pH was 7.6 ± 0.1. The viscosity of the formulation presented a mean value of 4.0 ± 0.1 mPa s within the shear rate interval of 200–1000 s−1 at 33 °C. Cell viability remained higher than 90% in both cell lines. No discomfort or clinical signs were observed in rabbits. Conclusions The liposome-based and in situ gelling artificial tear formulation presented good tolerance and suitable properties for topical ophthalmic administration. It may be beneficial in the treatment of dry eye disease.

BACKGROUND: The use of contact lenses has increased in recent years as has the incidence of Dry Eye Syndrome, partly due to their use. Artificial tears are the most common treatment option. Since these changes can facilitate Acanthamoeba infection, the present study has been designed to evaluate the effect of three artificial tears treatments in the viability of Acanthamoeba genotype T4 trophozoites. Optava Fusion™, Oculotect®, and Artelac® Splash were selected due to their formulation. METHODS: Viability was assessed using two staining methods, Trypan Blue stain and CTC stain at different time intervals (2, 4, 6, 8 and 24 h). Trypan Blue viability was obtained by manual count with light microscopy while the CTC stain was determined using flow cytometry. RESULTS: Trypan Blue staining results demonstrated a decrease in viability for Optava Fusion™ and Artelac® Splash during the first 4 h of incubation. After, this effect seems to lose strength. In the case of Oculotect®, complete cell death was observed after 2 h. Using flow cytometry analysis, Optava Fusion™ and Oculotect® exhibited the same effect observed with Trypan Blue staining. However, Artelac® Splash revealed decreasing cell respiratory activity after four hours, with no damage to the cell membrane. CONCLUSIONS: The present study uses, for the first time, CTC stain analyzed by flow cytometry to establish Acanthamoeba viability demonstrating its usefulness and complementarity with the traditional stain, Trypan Blue. Artelac® Splash, with no preservatives, and Optava Fusion TM, with Purite®, have not shown any useful amoebicidal activity. On the contrary, promising results presented by Ocultect®, with BAK, open up a new possibility for Acanthamoeba keratitis prophylaxis and treatment although in vivo studies should be carried out. This project was supported by Grant PI12/ 02725 from Instituto de Salud Carlos III (FISS) and FEDER by grant USPCEU-PC07/2013 of the Fundación Universitaria San Pablo CEU and by grant CEU-Banco de Santander. TSG was supported by Research Program EADS Construcciones Aeronáuticas S.A. - Brasil I and by CAPES/Brazil (Grant BEX 9132/13-9). Sí

SIGNIFICANCE Reliable intraocular pressure (IOP) measurement after intrastromal corneal ring segments (ICRS) implantation is a challenge because of altered corneal morphology. In this study, IOP is measured with four tonometers, compared with Goldmann applanation tonometry (GAT) values and the influence of corneal parameters is established. PURPOSE This study compares IOP measurements made using different tonometers in patients implanted with ICRS and assesses the effects of central corneal thickness (CCT), corneal curvature, and corneal astigmatism on the IOP measurements obtained. METHODS In this cross-sectional study, IOP was measured using three different tonometers in 91 eyes of 91 patients with corneal ectasia implanted at least 6 months previously with ICRS. The tonometers tested were the TonoPen XL, Pascal dynamic contour tonometer (DCT), and iCare Pro rebound tonometer. GAT measurements were used as reference. Agreement among the IOPs provided by the different tonometers and the influence of corneal variables on the IOP measurements obtained were assessed using the Bland-Altman method, intraclass correlation coefficients, and multiple linear regression analysis. RESULTS Mean IOP differences were GAT versus TonoPen XL -0.8 ± 3.07 mm Hg, GAT versus DCT -1.0 ± 3.26 mm Hg, and GAT versus iCare Pro 0.8 ± 2.92 mm Hg. Our multiple linear regression analysis identified CCT as a confounding factor affecting all the tonometer readings but DCT-IOP. CONCLUSIONS In patients fitted with ICRS, IOP measurements made using the iCare Pro and TonoPen XL showed most agreement with GAT. Intraocular pressure measurements made by DCT were unaffected by corneal topographic factors though this procedure slightly overestimated GAT readings.

Purpose To examine the diagnostic accuracy and performance of Uvemaster, a mobile application (app) or diagnostic decision support system (DDSS) for uveitis. The app contains a large database of knowledge including 88 uveitis syndromes each with 76 clinical items, both ocular and systemic (total 6688) and their respective prevalences, and displays a differential diagnoses list (DDL) ordered by sensitivity, specificity, or positive predictive value (PPV). Methods In this retrospective case-series study, diagnostic accuracy (percentage of cases for which a correct diagnosis was obtained) and performance (percentage of cases for which a specific diagnosis was obtained) were determined in reported series of patients originally diagnosed by a uveitis specialist with specific uveitis (N = 88) and idiopathic uveitis (N = 71), respectively. Results Diagnostic accuracy was 96.6% (95% confidence interval [CI], 93.2-100). By sensitivity, the original diagnosis appeared among the top three in the DDL in 90.9% (95% CI, 84.1-96.6) and was the first in 73.9% (95% CI, 63.6-83.0). By PPV, the original diagnosis was among the top DDL three in 62.5% (95% CI, 51.1-71.6) and the first in 29.5% (95% CI, 20.5-38.6; P < 0.001). In 71 (31.1%) patients originally diagnosed with idiopathic uveitis, 19 new diagnoses were made reducing this series to 52 (22.8%) and improving by 8.3% the new rate of diagnosed specific uveitis cases (performance = 77.2%; 95% CI, 71.1-82.9). Conclusions Uvemaster proved accurate and based on the same clinical data was able to detect more cases of specific uveitis than the original clinician only-based method.

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Purpose To compare intraocular pressure (IOP) measurements made using 5 tonometers in keratoconic eyes with and without intrastromal corneal ring segments. Methods and patients This was an observational case series study. A total of 147 eyes of 147 patients with keratoconus, 74 of which had undergone corneal ring segment placement, were prospectively evaluated. IOP was measured using the tonometers Tonopen XL, Pascal dynamic contour tonometer, iCare Pro, ocular response analyzer (ORA), and Goldmann applanation (GAT) in random order. The Bland-Altman method was used to examine interinstrument agreement. Effects on readings of central corneal thickness, corneal curvature, and corneal astigmatism were assessed by multivariate regression analysis. Results Smallest mean IOP differences with GAT measurements in eyes without and with ring segments, respectively, were detected for iCare Pro [0.2 (2.9) mm Hg and 0.4 (3.0) mm Hg, P=0.914] and greatest differences for ORA Goldmann-correlated IOP [5.8 (3.3) mm Hg and 6.0 (3.1) mm Hg, P=0.363]. Best agreement with GAT was shown by iCare Pro (ICC=0.829; 95% CI, 0.721-0.896) and worse agreement by ORA corneal-compensated IOP (ICC=-0.145; 95% CI, -0.826 to 0.283). All but the dynamic contour tonometer readings were influenced by central corneal thickness, yet these measurements were affected by the presence of ring segments (P=0.017) and corneal astigmatism (P=0.030). Corneal curvature only affected ORA Goldmann-correlated IOP (P=0.029). Conclusions All 5 tonometers provided reliable IOP readings in the keratoconic eyes regardless of the presence of corneal ring segments. iCare Pro readings were most consistent with GAT, whereas ORA readings were least consistent with this reference standard.

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.

Purpose To assess in uveitis patients the rate of immunosuppressive drug (ISD) discontinuation in real-life clinical practice, comparing this rate among ISDs. Design Longitudinal retrospective cohort study. Methods We included uveitis patients attending a tertiary eye referral center from Madrid (Spain) between 1989 and 2015, prescribed any ISDs (cyclosporine, methotrexate, azathioprine, anti-TNF drugs, or others). Our main outcome was discontinuation of all ISDs owing to clinical efficacy, inefficacy, adverse drug reaction (ADR), and other medical causes. Discontinuation rates (DRs) per 100 patient-years were estimated. Variables associated with specific-cause discontinuations were analyzed using Cox bivariate and multivariate models. Results We analyzed 110 patients with 263 treatment courses and 665.2 patient-years of observation. Cyclosporine (66.4%), methotrexate (47.3%), azathioprine (30.9%), and anti-TNFs (30.9%) were the most frequently used ISDs. Treatment was suspended in 136 cases (mostly owing to clinical efficacy [38.2%], inefficacy [26.5%], and ADRs [22.8%]). All-cause DR with 95% confidence interval was 20.4 [17.3–24.2]. Retention rates at 1 and 10 years were 74% and 16%, respectively. In the multivariate analysis, combined treatment exhibited higher DRs owing to clinical efficacy than other ISDs in monotherapy. Conversely, nonbiologic combination therapy with azathioprine exhibited the highest DR owing to ADRs. Conclusions Clinical efficacy was the most frequent cause for ISD discontinuation, followed by inefficacy and ADRs. DR owing to efficacy was higher for combination therapy. Furthermore, nonbiologic combination therapy with azathioprine was associated with a higher DR owing to ADRs.

This article discusses current practice in the treatment of conjunctivitis and how the use of topical moxifloxacin can increase therapeutic effectiveness, reduce treatment failures and, consequently, be cost effective and reduce the societal burden of the disorder. Current practice and effectiveness data were derived from the literature. Data on healthcare utilization as a result of treatment failure were collected by survey and the cost of treatment was defined using national costings. A decision-analytic model to assess cost effectiveness was developed and the impact on the healthcare budget was calculated to define the health economic impact. Bacterial conjunctivitis represents a significant health problem and accounts for an estimated 1-1.5% of primary-care consultations. The disorder is highly contagious and causes a substantial healthcare and societal burden. Bacterial conjunctivitis is generally self-limiting, resolving within 1-2 weeks. However, the use of antibacterials significantly improves clinical and microbiological remission, shortens symptom duration, and enables more effective use of healthcare resources, compared with placebo. From a health economic perspective this benefits the healthcare system and society, since fewer healthcare resources are needed and the adult affected, or the parent/caregiver of the child affected, can return to full work capacity sooner, reducing loss of productivity. Treatment strategies vary significantly between countries. Most patients are first seen in primary care, where 'wait-and-see', lubrification and antiseptic or antibacterial treatment is provided. In Europe, when antibacterials are prescribed most general practitioners (GPs) prescribe a broad-spectrum topical antibacterial. The most commonly used drugs are chloramphenicol and fusidic acid, with fluoroquinolones rarely reported as first-line treatment by GPs. At the specialist (ophthalmologist) level, or for second-line treatment at the GP level, topical antibacterials are frequently used. However, in most countries, topical fluoroquinolones, particularly those recently approved by the European Medicines Agency, such as topical levofloxacin and topical moxifloxacin, are rarely used and instead are reserved for use as a last resort. In other parts of the world topical lomefloxacin, gatifloxacin and/or besifloxacin are also available. The strategy of using novel topical fluoroquinolones as a last resort reflects a belief that the use of topical fluoroquinolones may enhance the development of resistance, jeopardizing future availability of antibacterial treatment for ocular infections. In fact, most cases of bacterial resistance arise as a result of systemic treatment. Thus, this concern should not be extrapolated to topical use of fluoroquinolones, which results in antibacterial concentrations at the ocular surface that can significantly exceed mutant prevention concentrations. In addition, with products such as topical moxifloxacin, a dual-step mutation is required for resistance to emerge. Moxifloxacin restricts the selection of resistant mutants, meaning that emergence of resistance is unlikely. The strategy of not using the most effective fluoroquinolones such as topical moxifloxacin may lead to more patients with no improvement or worsening of symptoms, requiring re-intervention, additional examination and new treatment; these outcomes are defined as 'treatment failures'. Treatment failures cause an extra societal burden and increased costs due to the extra healthcare resources required (additional GP/specialist visits, laboratory tests, additional treatment, etc.). Compared with non-fluoroquinolones, topical moxifloxacin has a higher potency and faster in vitro 'speed-to-kill'. It has also been shown that, within the fluoroquinolone class, topical moxifloxacin and besifloxacin achieve the highest mean concentrations in conjunctival tissue, have the longest residence times and display favourable area under the concentration-time curve from time zero to 24 hours (AUC(24))/minimum inhibitory concentration ratio required to inhibit the growth of 90% of organisms (MIC(90)) and thus favourable pharmacokinetic/pharmacodynamic characteristics. This can result in reduced time-to-cure and a lower number of treatment failures, leading to better disease management and a healthcare-economic benefit arising from the associated reduction in utilization of healthcare resources. The high potency and mean concentration in conjunctival tissue combined with the long residence time of topical moxifloxacin enables a dosing strategy of three times daily for 5 days. Topical moxifloxacin is also the first ophthalmic antibacterial in Europe provided as a multidose, self-preserved, topical solution, thus avoiding the risk of benzalkonium chloride preservative-related allergic reactions and swelling. In addition, topical moxifloxacin has a near neutral pH (6.8) and is well tolerated by patients. Given the characteristics of the novel topical fluoroquinolones, a change in the healthcare treatment strategy for acute infectious conjunctivitis is to be recommended. Topical application of fluoroquinolones, such as moxifloxacin multidose self-preserved solution, should be considered earlier in the treatment path for conjunctivitis. Notwithstanding the premium price attached to this novel topical antibacterial, use of topical moxifloxacin for bacterial conjunctivitis can be cost effective and even generate total healthcare budget savings by reducing both the costs of managing treatment failures and the use of clinicians' time to manage such failures.

To compare the effects of Viscofresh 0.5% (carmellose sodium 0. 5%) versus Lubristil (sodium hyaluronate 0.15%) in dry eye syndrome and to study the influence of these two treatments on the expression of various inflammatory markers by flow cytometry in impression cytology specimens.In this randomized, masked-observer, parallel group, single-center study, 15 patients with dry eye syndrome were randomized to sodium carmellose 0.5% or sodium hyaluronate 0.15% 1-month treatment after a 1-week washout period. Corneal staining with flurescein, breakup time, Schirmer 1 test with anesthesia (Jones test), and tear clearance were assessed. Besides, conjunctival impression cytology was performed to investigate inflammatory markers (CD3, CD11b, and HLA-DR) using flow cytometry.Carmellose group shows statistical improvement compared with the hyaluronate group in breakup time, corneal staining, and HLA-DR. The two other inflammatory markers had also a tendency for a decreased expression in both groups, with no statistical significance. There were neither visual acuity loss nor other complications related to treatment.Both artificial tears improve dry eye signs and symptoms and inflammatory markers expression, with significant better results in carmellose group.

Background This study was done to evaluate the visual and anatomical outcomes of topical regenerating agents as a novel therapy for neutrophic corneal ulcer (NCU) secondary to acanthamoeba infection. Findings A 20-year-old woman with a history of contact lens wear was referred to our hospital for keratitis after responding poorly to conventional treatment. In vivo confocal microscopy images suggested acanthamoeba keratitis with double-walled cysts in the anterior corneal stroma. Acanthamoeba infection was confirmed by laboratory findings. She was started on 0.1 % propamidine and 0.02 % chlorhexidine drops every hour. The antibiotic and antifungal drops were stopped when bacterial and fungal cultures proved negative. A central neurotrophic corneal ulcers (NCU) appeared, and despite treatment with artificial tears, bandage contact lens, and autologous serum, the ulcer worsened and she was treated with topical CACICOL20 (1 drop every 2 days) for 8 weeks. The corneal defect was completely repaired in 3 weeks. The treatment was well tolerated, and no local or systemic side effects were noted. Visual acuity remained 20/400. Two months later, the defect was still closed and the patient continued with 0.1 % propamidine and 0.02 % chlorhexidine drops, bandage contact lens, artificial tears, and autologous serum. Conclusions Topical regenerating agents interact with components of the extracellular matrix, binding matrix proteins and protecting them from proteolysis, restoring the matrix environment, and improving tissue healing. In this case, CALCICOL20 was effective for vision stabilization, wound healing, and was well tolerated for NCU secondary to acanthamoeba infection.

Purpose: To evaluate contrast sensitivity and disability glare in patients with dry eye using the Contrast Glaretester 1000. Methods: Contrast sensitivity and disability glare were determined in 33 eyes of 33 patients with dry eye and 30 eyes of 30 healthy control subjects for six target sizes with a visual angle of 6.3–0.7 degrees using the Contrast Glaretester 1000, whose working mechanism is similar to that of the conventional perimetry instrument. Results: Contrast sensitivity was significantly worse in dry eye group when viewing all target sizes (reduction of 0.10–0.25 log contrast units, p

To evaluate the long-term efficacy and safety of infliximab as treatment for noninfectious posterior uveitis. An open-label clinical trial including seven patients (12 eyes) with posterior uveitis refractory to conventional treatment regimens with corticosteroids and at least one immunosuppressive agent. Three intravenous doses of 5 mg/kg of infliximab were administered at weeks 0, 2, and 6. Infliximab infusion was repeated in patients undergoing a relapse of uveitis after initial remission. Improvement was defined as amelioration of visual acuity or disappearance of retinal exudates and/or haemorrhages, decreased macular oedema and/or vitreous opacities. All patients were followed up for at least 36 months. Six of the seven patients (five diagnosed with Behcet's disease and one diagnosed with sarcoidosis) showed a significant improvement after the first infliximab dose. Only in one patient diagnosed with chronic idiopathic multifocal choroiditis did the drug have no effect, and this patient was withdrawn from the study. At the end of follow-up, one eye had lost one line of vision and three eyes showed improved vision. All eyes had improved in terms of signs of inflammation. No adverse effects of treatment were observed. Infliximab is efficient and safe for the long-term management of refractory posterior uveitis, especially in patients with predominant retinal vasculitis and vitritis.

Purpose To compare selective laser trabeculoplasty (SLT) with conventional argon laser trabeculoplasty (ALT) in terms of hypotensive efficacy, anterior chamber inflammation, and pain reported by the patients treated. Methods A prospective study performed on 40 consecutive patients. Group I (n=20): SLT 180°. Group II (n=20): ALT 180°. Intraocular pressure, flare (Laser-Flare-Meter, Kowa FM-500, Japan), and pain (Visual Analogue Scale) were measured before treatment and 1 h, 24 h, 1 week, and 1, 3 and 6 months after treatment. Statistically significant differences were determined by an independent-sample Student's t-test. Results At 6 months after treatment, pressure reduction was similar in both groups: SLT 22.2% (range 0–36.3%) and ALT 19.5% (range 0–30.2%), P=0.741. The energy released during treatment was significantly lower in SLT (48.3 SD 7.4 mJ) than in ALT (4321 SD 241.7 mJ), P

To evaluate the loss of lens transparency incurred by patients undergoing trabeculectomy.A prospective cohort study.Data corresponding to 33 eyes of 33 consecutive patients with primary open-angle glaucoma (POAG) subjected to trabeculectomy (group 1) were compared with those corresponding to 12 eyes of 12 patients with POAG receiving topical antiglaucomatous treatment (group 2).Lens fluorophotometry was performed on the group 1 patients before and 12 months after surgery. In group 2, fluorophotometry was conducted at the onset of the study and at 12 months of follow-up.Starting and final lens autofluorescence and transmittance values corresponding to each subject group were compared.In group 1, starting and final autofluorescence was 556.3 +/- 184.3 and 691.1 +/- 179.3 Eq ng/ml, and starting and final transmittance was 0.78 +/- 0.11 and 0.67 +/- 0.14, respectively. Respective values for group 2 were 574.3 +/- 94.8 and 595.2 +/- 107.0 Eq ng/ml and 0.72 +/- 0.17 and 0.71 +/- 0.16. The mean change between final and initial autofluorescence was statistically different between groups (134.7 +/- 123.7, group 1, 20.9 +/- 25.1 Eq ng/ml, group 2; P0.001). Similarly, a significant difference (P0.001) in transmittance change was observed between the surgery and control groups (-0.11 +/- 0.072, group 1; 0.02 +/- 0.008, group 2)It was demonstrated by lens fluorophotometry that trabeculectomy in POAG leads to a loss in lens transparency.

Objective To assess the safety of posterior chamber phakic intraocular lens (PCPIOL) implantation in patients with high myopia. Design Prospective, noncomparative, interventional case series. Participants Twenty eyes of 10 patients were included. Intervention Staar Collamer Implantable Contact Lens PCPIOLs were implanted for the correction of high myopia. Main outcome measures Intra- and postoperative complications were recorded. Specular microscopy, lens fluorophotometry, laser flare-meter, and ultrasound biomicroscopy were performed before surgery and at different stages of the follow-up period to evaluate endothelial cell density, crystalline lens transmittance, aqueous flare, and anatomic relations of the implanted lenses with the other structures of the anterior segment. Results There were no intraoperative complications. One patient experienced pupillary entrapment by the lens in the immediate postoperative period, which was resolved without incident. Pigmentary dispersion or cataracts did not appear during the postoperative period. All the lenses remained correctly centered, and no patient reported night halos or glare. Anterior chamber depth showed a statistically significant reduction, between 9% and 12%. Central endothelial density was significantly decreased after surgery. The percentages of cell loss after 3, 6, 12, 18, and 24 months were 4.41%, 4.83%, 5.17%, 5.46%, and 6.57%, respectively. Aqueous flare increased by 49.19% in the first postoperative month in relation to preoperative values. Afterward, it decreased and then remained above preoperative values for the entire follow-up period (33.76% at month 3, 27.81% at month 6, 27.65% at month 12, 23.39% at month 18, and 27.27% at month 24). Crystalline lens transmittance decreased by 0.72% at month 3, by 1.44% at month 6, by 1.95% at month 12, by 2.25% at month 18, and by 2.24% at month 24. Finally, by ultrasound biomicroscopy it was observed that the PCPIOL and the crystalline lens were in contact on the peripheral level in 12 patients (60%) and in the center in another three patients (15%) during at least one checkup. In all the patients, contact between the PCPIOL and the posterior iris surface could be observed. Conclusions Posterior chamber phakic IOL implantation for the surgical correction of high myopia is a safe procedure with regard to immediate visual and refractive results. The short-term clinical benefit and lack of immediate surgical complications are impressive. However, the increase in flare, the endothelial cell loss, the decrease in crystalline lens transmittance, and the iris–PCPIOL and crystalline lens–PCPIOL contact are findings that suggest caution regarding the long-term safety of this lens implant.

PURPOSE: To identify the presence of silver deposits in the cornea using a new-generation confocal microscopy technique. METHODS: Case report. RESULTS: A 70-year-old man, who had been a jeweler for many years, was referred to our center for assessment of corneal opacity and ocular pigmentation. Slit-lamp examination revealed grayish, dense confluent deposits in the central and peripheral cornea, deep stroma, and Descemet's membrane. On confocal microscopy, we observed typical images of hyperreflective keratocytes across the entire stromal surface and two hyperreflective plaques coinciding with areas of metal deposition, one at Descemet's membrane and the other at Bowman's membrane. This last deposition site has not been previously identified in vivo by confocal microscopy. CONCLUSIONS: Confocal microscopy is a useful tool for the diagnosis of corneal argyrosis because it allows the in vivo visualization of silver deposits at different corneal levels.

Purpose To assess the effects of sulfasalazine in preventing recurrences and reducing the severity of anterior uveitis associated with ankylosing spondylitis and chronic intestinal inflammation. Methods Twenty-two patients with anterior uveitis associated with ankylosing spondylitis were studied. Ten patients were randomised to receive oral sulfasalazine (group 1) and 12 patients randomised to no treatment (group 2); all were followed for 3 years. Blood-aqueous barrier permeability was determined by fluorophotometry and bowel biopsies were taken. Results A statistically significant difference was observed between the two groups regarding the number of recurrences of uveitis (p = 0.016). The blood-aqueous barrier permeability was significantly higher during acute attacks in group 2 (group 1: 31.3 +/- 26.4 x 10(-4) min-1 vs group 2: 66.2 +/- 28.5 x 10(-4) min-1; p = 0.019) but not during the disease-free period. We observed a higher incidence of chronic intestinal inflammation at the end of the study in group 2 (group 1: 3/8 vs group 2: 7/9, p = 0.153). No relation was observed between blood-aqueous barrier permeability and the number of recurrences. The number of patients with severe persistent posterior synechiae at the end of the study was higher in group 2 (group 1: 4 patients before and 4 patients at the end; group 2: 4 patients before and 8 patients at the end; p = 0.65). Conclusion Sulfasalazine may be beneficial in preventing recurrences and reducing the severity of anterior uveitis associated with ankylosing spondylitis.