Comparative study on the effect of hyperthermic massage and mechanical squeezing in the patients with mild and severe meibomian gland dysfunction: An interventional case series.

BACKGROUND: Meibomian glands exist beneath the palpebral conjunctiva; thus, it is invisible to the naked eye without infrared imaging. This study used meibography to group patients with meibomian gland dysfunction (MGD) and assessed the effects of hyperthermic massage and mechanical squeezing in both groups. MATERIALS AND METHODS: Patients with MGD were divided into two groups, according to the degree of meibomian gland loss: group 1, in which the sum of eyelid scores ranged from 0 to 4 (mild to moderate gland loss) and group 2, in which the sum of eyelid scores ranged from 5 to 6 (severe gland loss). Hyperthermic massage and mechanical squeezing were given to both groups once a week for 4 weeks, and only non-preservative artificial tears were allowed. Ocular surface disease index (OSDI), Schirmer's test, meibography score, tear break-up time (TBUT), ocular surface staining, expressible meibomian gland, and quality before and after treatment were compared. RESULTS: Of the 49 patients who completed the 4 weeks of treatment and the evaluation at week 5, 29 were assigned to group 1 and 20 were assigned to group 2. Meibography scores, OSDI, TBUT, and expressibility of meibum had significant differences before and after treatments in both groups. However, there was no significant difference between the changes in clinical signs between group 1 and 2 after treatment. Without grouping, all patients showed significant decreases in meibography score, OSDI, cornea staining score, and increases in TBUT and expressibility of meibum after treatment. CONCLUSIONS: Considering the results of the current study, hyperthermic massage and mechanical squeezing may be effective in patients with meibomian gland loss, regardless of the degree of severity.

Long term observation of ocular surface alkali burn in rabbit models: Quantitative analysis of corneal haze, vascularity and self-recovery.

Limbal Stem Cell Deficiency (LSCD), caused due to corneal injury, primarily by chemical/alkali burns, leads to compromised vision. Recently, several animal models of corneal alkali burn injury have become available. The majority of the studies with these animal models start interventions soon after the injury. However, in the clinical setting, there is a considerable delay before the intervention is initiated. Detailed knowledge of the molecular, histopathological, and clinical parameters associated with the progression of the injury leading to LSCD is highly desirable. In this context, we set out to investigate clinical, histopathological parameters of ocular surface alkali burn over a long period of time, post-injury. Limbal stem cell-deficient animal models of rabbits were created by alkali burn using sodium hydroxide, which was then assessed for their progression towards LSCD by grading the alkali burn, corneal haze, and vascularization. Additionally, cells present on the corneal surface after the burn was investigated by histology and immunophenotyping. Grading of rabbit eyes post-alkali burn had shown complete conjunctivalization in 80% (n = 12/15) of the rabbits with the alkali burn grade score of 3.88 ± 0.29 in three months and remained stable at four months (4.12 ± 0.24). However, ocular surface showed self-healing in 20% (n = 3/15) of the rabbits with a score of 1.67 ± 0.34 in four months irrespective of similar alkali injury. These self-healing corneas exhibited decreased opacity score from 2.51 ± 0.39 to 0.66 ± 0.22 (p = 0.002) and regressed vascularity from 1.66 ± 0.41 to 0.66 ± 0.33 in one to nine months, respectively. Restoration of the corneal phenotype (CK3+) was observed in central and mid-peripheral regions of the self-healing corneas, and histology revealed the localization of inflammatory cells to the peripheral cornea when compared to conjunctivalized and scarred LSCD eyes. Our study shows the essentiality to consider the time required for surgical intervention after the corneal alkali injury in rabbit models as evident from their tendency to self-heal and restore corneal phenotype without therapy. Such information on the possibility of self-healing should be useful in further studies as well as determining interventional timings and strategy during clinical presentation of corneal alkali burns.

The correction of conjunctivochalasis using high-frequency radiowave electrosurgery improves dry eye disease.

We aimed to determine the clinical impact of conjunctivochalasis (CCh) and its correction using high-frequency radiowave electrosurgery (HFR-ES), for signs and symptoms of dry eye disease (DED). Forty patients diagnosed with symptomatic CCh were prospectively enrolled. As a result, patients with CCh had moderate to severe DED and most of them exhibited meibomian gland dysfunction (MGD). Corneo-conjunctival fluorescein staining score (CFS) and all lid-parallel-conjunctival-folds scores (LIPCOFs) were positively correlated. Nasal LIPCOF significantly correlated with symptoms and tear volume. Central, temporal, and total LIPCOF significantly correlated with MG loss, MGD stage, and lipid layer thickness. Independent significant factors associated with total LIPCOF included CFS, tear break-up time, and MGD stage. One month following HFR-ES, CCh was completely resolved in all cases. Patient age and preoperative nasal LIPCOF were determinants of outcomes associated with postoperative improvements in symptoms. Ocular surface parameters significantly improved, but MGD-related signs did not. Collectively, CCh associated with MGD severity deteriorates not only tear film stability and reservoir capacity, leading to DED exacerbation. Therefore, CCh should be corrected in patients with DED and MGD. Younger patients with nasal CCh are likely to experience more symptomatic relief after HFR-ES. Particularly, management for MGD should be maintained after CCh correction.

Bleb plication: a minimally invasive repair method for a leaking ischemic bleb after trabeculectomy.

Bleb leakage is a serious complication of glaucoma filtering surgery. This study describes the method and the results of a new repair method for ischemic bleb leaks. The subjects were consecutive eleven eyes of 11 patients with bleb leakage who underwent the bleb plication surgery. The bleb plication surgery consisted of two steps: 1) bleb needle redirection to float the conjunctiva away from the sclera as extensively as possible around the ischemic conjunctiva; and 2) multiple "O-shaped" sutures were applied between the non-ischemic conjunctiva just outside the ischemic conjunctiva and corneal limbus. The ischemic conjunctiva was not removed, but undermined beneath the advanced non-ischemic conjunctiva. This bleb plication method was repeated until the leakage was sealed. All patients were followed up for at least 6 months after final bleb plication. After final bleb plication, no recurrence of bleb leakage was observed. Moreover, ischemic changes were no longer observed in the advanced non-ischemic conjunctiva. Pre-operative and final intraocular pressure was 3.2 ± 4.1 and 11.9 ± 2.8 mmHg, respectively. This new repair method of bleb plication was safe and effective in sealing the leakage. The conjunctiva is not excised, and hence it does not run out.

Conjunctival reconstruction via enrichment of human conjunctival epithelial stem cells by p75 through the NGF-p75-SALL2 signaling axis.

Severe conjunctival diseases can cause significant conjunctival scarring, which seriously limits eye movement and affects patients' vision. Conjunctival reconstruction remains challenging due to the lack of efficient methods for stem cells enrichment. This study indicated that p75 positive conjunctival epithelial cells (CjECs) were mainly located in the basal layer of human conjunctival epithelium and showed an immature differentiation state in vivo. The p75 strongly positive (p75++) CjECs enriched by immuno-magnetic beads exhibited high expression of stem cell markers and low expression of differentiated keratins. During continuous cell passage cultivation, p75++ CjECs showed the strongest proliferation potential and were able to reconstruct the conjunctiva in vivo with the most complete structure and function. Exogenous addition of NGF promoted the differentiation of CjECs by increasing nuclear localization of SALL2 in p75++ CjECs while proNGF played an opposite role. Altogether, p75++ CjECs present stem cell characteristics and exhibit the strongest proliferation potential so can be used as seed cells for conjunctival reconstruction, and NGF-p75-SALL2 signaling pathway was involved in regulating the differentiation of CjECs.

A Custom Multiphoton Microscopy Platform for Live Imaging of Mouse Cornea and Conjunctiva.

Conventional histological analysis and cell culture systems are insufficient to simulate in vivo physiological and pathological dynamics completely. Multiphoton microscopy (MPM) has become one of the most popular imaging modalities for biomedical study at cellular levels in vivo, advantages include high resolution, deep tissue penetration and minimal phototoxicity. We have designed an MPM imaging platform with a customized mouse eye holder and a stereotaxic stage for imaging ocular surface in vivo. Dual fluorescent protein reporter mouse enables visualization of cell nuclei, cell membranes, nerve fibers, and capillaries within the ocular surface. In addition to multiphoton fluorescence signals, acquiring second harmonic generation (SHG) simultaneously allows for the characterization of collagenous stromal architecture. This platform can be employed for intravital imaging with accurate positioning across the entire ocular surface, including cornea and conjunctiva.

Tropism, replication competence, and innate immune responses of the coronavirus SARS-CoV-2 in human respiratory tract and conjunctiva: an analysis in ex-vivo and in-vitro cultures.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019, causing a respiratory disease (coronavirus disease 2019, COVID-19) of varying severity in Wuhan, China, and subsequently leading to a pandemic. The transmissibility and pathogenesis of SARS-CoV-2 remain poorly understood. We evaluate its tissue and cellular tropism in human respiratory tract, conjunctiva, and innate immune responses in comparison with other coronavirus and influenza virus to provide insights into COVID-19 pathogenesis. METHODS: We isolated SARS-CoV-2 from a patient with confirmed COVID-19, and compared virus tropism and replication competence with SARS-CoV, Middle East respiratory syndrome-associated coronavirus (MERS-CoV), and 2009 pandemic influenza H1N1 (H1N1pdm) in ex-vivo cultures of human bronchus (n=5) and lung (n=4). We assessed extrapulmonary infection using ex-vivo cultures of human conjunctiva (n=3) and in-vitro cultures of human colorectal adenocarcinoma cell lines. Innate immune responses and angiotensin-converting enzyme 2 expression were investigated in human alveolar epithelial cells and macrophages. In-vitro studies included the highly pathogenic avian influenza H5N1 virus (H5N1) and mock-infected cells as controls. FINDINGS: SARS-CoV-2 infected ciliated, mucus-secreting, and club cells of bronchial epithelium, type 1 pneumocytes in the lung, and the conjunctival mucosa. In the bronchus, SARS-CoV-2 replication competence was similar to MERS-CoV, and higher than SARS-CoV, but lower than H1N1pdm. In the lung, SARS-CoV-2 replication was similar to SARS-CoV and H1N1pdm, but was lower than MERS-CoV. In conjunctiva, SARS-CoV-2 replication was greater than SARS-CoV. SARS-CoV-2 was a less potent inducer of proinflammatory cytokines than H5N1, H1N1pdm, or MERS-CoV. INTERPRETATION: The conjunctival epithelium and conducting airways appear to be potential portals of infection for SARS-CoV-2. Both SARS-CoV and SARS-CoV-2 replicated similarly in the alveolar epithelium; SARS-CoV-2 replicated more extensively in the bronchus than SARS-CoV. These findings provide important insights into the transmissibility and pathogenesis of SARS-CoV-2 infection and differences with other respiratory pathogens. FUNDING: US National Institute of Allergy and Infectious Diseases, University Grants Committee of Hong Kong Special Administrative Region, China; Health and Medical Research Fund, Food and Health Bureau, Government of Hong Kong Special Administrative Region, China.

Femtosecond Laser-assisted Preparation of Conjunctival Autograft for Pterygium Surgery.

Femtosecond laser-assisted conjunctival autografts (CAG) preparation was recently proposed. This study reports the outcomes of the first clinical trial on the use of laser to prepare CAG in pterygium surgery, and to compare the outcomes with those of manual technique. Forty eyes undergoing primary pterygium excision with laser-assisted CAG transplantation were prospectively included (L group). Two historical matched cohorts whose CAGs were prepared manually were compared (n = 78 eyes by the same experienced surgeon, M group; n = 78 eyes by trainees; TM group). We found the laser-created CAGs had only 11 µm deviation from the targeted thickness. The best-corrected visual acuity improved, and the astigmatism significantly decreased after surgery, with comparable efficacy across 3 groups. The 1-year recurrence rate was 2.5%, 3.8% and 7.7% in the L, M and TM groups, respectively (P = 0.12). There was no significant difference between the L and M groups in the complication rate (5.0% and 1.3%, respectively), surgical time (19.4 ± 5.1 and 19.1 ± 6.2 minutes, respectively), and postoperative discomfort scores (0.1 ± 0.3 and 0.2 ± 0.3, respectively), but these outcomes were significantly less favorable in the TM group. The results of this first comparative clinical trial suggest that femtosecond laser-assisted CAG preparation can be considered as an alternative technique for CAGs preparation.

Blood derived treatment from two allogeneic sources for severe dry eye associated to keratopathy: a multicentre randomised cross over clinical trial.

AIM: To compare the efficacy of cord blood and peripheral adult donor blood serum eyedrops, controlled for growth factor content, in the treatment of severe dry eye diseases (DED) resistant to conventional therapy. METHODS: This was a multicentre randomised, double-masked, cross-over clinical trial. Sixty patients diagnosed as severe DED, associated to persistent corneal epithelial defects were randomised and equally assigned to group A (treated with cord blood serum (CBS)) or group B (treated with PBS), eyedrops administered eight times/day for 1 month. Primary outcome was the pretreatment and post-treatment change in corneal fluorescein staining. Secondary outcomes included the pretreatment and post-treatment change in Ocular Surface Disease Index (OSDI) questionnaire and Visual Analogue Score (VAS) of subjective symptoms, Schirmer I test, tear break-up time and conjunctival staining. Patients with relapse in signs or symptoms after further 2 months switched to the remaining group for one additional month. Data were statistically analysed (p<0.05). RESULTS: Corneal staining was more significantly reduced after the CBS treatment, both VAS and OSDI score reduction was observed in both groups, but group A reported significantly less grittiness and pain. Nineteen patients shifted in the crossover period, the within individual comparison confirmed a better recovery in the CBS treatment period. Reduction in epithelial damage was positively associated with epidermal growth factor, transforming growth factorα and platelet-derived growth factor content. Levels of interleukins (IL-13) were positively associated with symptom decrease. CONCLUSIONS: Overall, DED signs improved after both CBS and PBS treatments, with potential advantages of CBS for subjective symptoms and corneal damage reduction. CLINICAL TRIAL REGISTRATION: NCT03064984.

Conjunctival microcirculation is associated with cerebral cortex microcirculation in post-resuscitation mild hypothermia: A rat model.

OBJECTIVE: This study aimed to compare the changes in sublingual and conjunctival microcirculation occurring with cerebral cortex microcirculation changes during mild hypothermia in a rat model of cardiac arrest. METHODS: Twenty-four rats were randomized into mild hypothermia (M) or normothermia (C) groups. Ventricular fibrillation was electrically induced and left untreated for 8 minutes, followed by 8 minutes of cardiopulmonary resuscitation. The core temperature in group M reduced to 33 ± 0.5°C at 13 minutes after restoration of spontaneous circulation and was maintained for 8 hours. In group C, the core temperature was maintained at 37 ± 0.2°C. The hemodynamics and microcirculation in the sublingual region, bulbar conjunctiva, and cerebral cortex were measured at baseline and 1, 2, 3, 4, 6, and 8 hours after restoration of spontaneous circulation. RESULTS: The M group showed significantly worse sublingual microcirculation at 6 hours post-resuscitation. However, microcirculation in the conjunctiva and cerebral cortex at 3 hours post-resuscitation were better in the M group. In the M group, microcirculation in the cerebral cortex was significantly correlated with that in the conjunctiva but not the sublingual microcirculation. CONCLUSIONS: Changes in conjunctival microcirculation are closely related to cerebral cortex microcirculation during mild hypothermia, indicating that cerebral cortex microcirculation could be monitored by measuring conjunctival microcirculation.

Topical Review: Effects of Contact Lens Wear on Corneal, Conjunctival, and Lid Margin Sensitivity.

SIGNIFICANCE: Contemporary soft contact lenses do not affect mechanical sensitivity of the cornea, whereas conjunctival sensitivity is increased compared with nonwearers. Orthokeratology lens wear, however, reduces corneal sensitivity. The effects of contact lenses on lid margin sensitivity are unclear, and the link between ocular surface sensitivity and discomfort requires further exploration.Although up to 50% of contact lens wearers experience discomfort with varying severity, impact, and frequency, the relationship between ocular surface sensitivity and ocular surface discomfort experienced during contact lens wear is unclear. The purpose of this review is to examine and summarize the current evidence for the impact of both historical and contemporary contact lens wear on ocular surface sensitivity, the etiology of changes in ocular surface sensitivity, contact lens wear-related factors associated with changes in ocular surface sensitivity, and the relationship between sensitivity and discomfort. Despite minimal effects on mechanical corneal sensitivity with contemporary soft contact lens wear, orthokeratology reduces corneal sensitivity through pressure-related effects. This review addresses the relevance of conjunctival and potentially lid margin sensitivity in tolerance and discomfort with contemporary lens wear and the impact of instrument and stimulus characteristics. Less invasive techniques particularly for lid margin sensitivity measurements are required. Given the potential interactions between a contact lens and the varied types of ocular surface nociceptors, instruments that allow for exploration of cold and chemical sensitivity particularly may better allow the effects of lens wear to be elucidated compared with those that explore high-threshold mechanical sensitivity alone. A better understanding of the relationships between lens wear and ocular surface sensitivity may result in improved management of contact lens discomfort.

Novel approaches to model effects of subconjunctival blebs on flow pressure to improve clinical grading systems after glaucoma drainage surgery.

Clinical grading systems following glaucoma filtration surgery do not include any effects of the bleb on the intra-ocular pressure and are relatively subjective, therefore carrying the risk of inter and/or intra-observer variability. The main objective of the study is to quantify and model the effect of subconjunctival bleb on flow pressure for assessment of clinical grading following glaucoma surgery. Subconjunctival bleb was created by inserting a tube into ex vivo rabbit eyes via an ab externo approach through the anterior chamber and exiting into the subconjunctival space. Sterile dyed water was injected through the tube into the developing bleb. For the in vitro approach a silicone bleb was created by clamping a circular silicone sheet, injecting dyed water through a fixed resistance outlet tube. Photographic measurements of the bleb height, planform area and pressure were taken as a function of time. Clinical blebs were also collected over a few months. Mathematical algorithm software was used to build the bleb model. Bleb height and volume increase as pressure in the bleb increases. The bleb planform area tended to a constant determined by the section of conjunctiva prior to shunt insertion. These increases were in accordance with the bleb model developed in the Appendix. They show that the pressure in the bleb is related to the resistance of the outflow. The linearity of clinical grading systems is reviewed and a new grading approach is proposed. The pressure in the bleb has a strong dependence on bleb extent, height and a weak dependence on conjunctival thickness. The pressure in a bleb can be estimated from bleb height, radius, and flow rate inlet in agreement with the bleb flow model. These results provide support for an improved bleb categorization system.

The histaminergic control of the iridal vascular tone in rats and its influencing by topical administration of olopatadine and ranitidine.

Objective. We evaluated the histamine's role in regulating the iris vasomotricity in rats, using as a research tool topical olopatadine, a selective H1 blocker, which is indicated for the treatment of allergic conjunctivitis and ranitidine, a selective H2 blocker mainly used for the treatment of peptic ulcer disease. Methods. Two groups of six Wistar rats anesthetized with ketamine 200 mg/kg body weight were used. They received distilled water in conjunctival instillations, initially and after 5 minutes, olopatadine 2.5 mmol/ l for the first group, respectively ranitidine 2.5 mmol/ l for the second group. The changes of the iris arteriolar and venular diameters were recorded. Results. Both olopatadine and ranitidine produced statistically significant iridal arteriolar vasoconstriction and ranitidine determined statistically significant venuloconstriction, while distilled water did not produce any statistically significant effect. Conclusions. There is a vasodilator histaminergic tone exerted through the histaminergic H1 and H2 receptors in the iris arterioles and, respectively, through the H2 receptors in the iridal venules. Olopatadine, a topical H1 antagonist used in the treatment of ocular allergies, may interfere with the humoral regulation of the iris arteriolar tone. Ranitidine, an H2 antagonist, decreased the diameter of the iris arterioles and venules, when administered topically in rats.

The influence of meibomian gland loss on ocular surface clinical parameters.

PURPOSE: To assess the relationship between the meibomian gland loss (MGL) and relevant ocular surface clinical parameters as well as the influence of age in this relationship. METHODS: A total of 161 participants (mean age; 42±17 years) were enrolled in this study. Infrared meibography was performed using Keratograph 5M (K5M; Oculus GmbH, Wetzlar). Participants were divided into five groups according to total meiboscore and the ocular surface parameters of each MGL group were studied. In addition, the relationship between MGL and the ocular surface parameters was established including age as covariant. RESULTS: Both eyelids were taken into account since no association between the MGL from upper and lower eyelid was found (k value=0.2; p=0.3) despite they were significantly correlated (r= 0.3; p<0.001). No statistically significant differences were found in symptomatology among different MGL groups. Statistically significant differences were found among MGL groups in tear osmolarity (p=0.02), bulbar redness (p=0.04), corneal and conjunctival staining (p=0.01 and p=0.004, respectively). Despite this, only corneal staining showed a significant correlation with MGL when age was covariant (r=0.2; p=0.04). CONCLUSIONS: MGL higher than 50% seems to be accompanied by signs on the ocular surface. Furthermore, age demonstrated to be a relevant factor when assessing MGL. For this reason, future studies should compare age-matched groups in order to know the contribution of the MGL on the ocular surface and establish valid cut-off values for dry eye diagnosis.

Ant Bites Conjunctival Tissue: The ABCs of Removing an Ocular Ant Foreign Body.

BACKGROUND: A variety of insect-related ocular injuries have been reported in the literature. However, no reports have been published documenting injuries resulting from exposure of the ocular surface to ants. This is surprising, given the relatively ubiquitous presence of ants. This is the first known case report to describe various techniques utilized in the removal of ants from the ocular surface. CASE REPORT: This case report details the presentation of a distressed 24-year-old woman who presented to the Emergency Department with an ocular foreign body associated with pain and increased lacrimation. She was identified to have an ant adherent to her conjunctiva. Various techniques of removal were performed, with the ant finally removed without any trauma to underlying tissues. CONCLUSION: This is the first case report to detail various techniques utilized in the removal of ants from the ocular surface, and discusses salient features that treating physicians should be aware of in managing patients presenting with ant bites.

One-Year Outcome Predictors of Strabismus Surgery from Anterior Segment Optical Coherence Tomography with Multiple B-Scan Averaging.

Strabismologists are eager to identify preoperative or intraoperative strabismus surgery outcome predictors because of the variable effects in each patient. Conjunctival closure position recession after rectus muscle recession is effective for correcting large angle strabismus. The elasticity of the conjunctiva and Tenon's capsule is important for strabismus surgery management. In this longitudinal study, we evaluated the prognosis of conjunctiva and Tenon's capsule thickness (CTT) near the limbus 1 year after strabismus surgery with a limbal conjunctival incision using swept-source anterior segment optical coherence tomography with multiple B-scan averaging. Also, we identified preoperative and/or intraoperative parameters associated with corrective effects 1 year after surgery in 15 consecutive treatment-naïve patients with exotropia or esotropia who underwent recession and resection. The 1-year CTT was greater than the preoperative CTT on the resection side (269 ± 111 vs 183 ± 53 µm, P < 0.001) but was smaller on the recession side (137 ± 54 vs 183 ± 71 µm, P = 0.02). The corrective effect of surgery (1.6 ± 0.3°/mm) was most strongly correlated with preoperative CTT on the recession side (P = 0.005, ß = -0.73). Hence, CTT on the recession side may provide adjunctive information for strabismus treatment.

Association between systemic activity index and dry eye severity in patients with primary Sjögren syndrome / A associação entre o índice de atividade sistêmica e a severidade do olho seco em pacientes com síndrome de Sjögren primária

ABSTRACT Purpose: The aim of the present study was to compare the severity of ocular and systemic findings among patients with primary Sjögren syndrome. Methods: The study followed a prospective controlled design and comprised two groups; the test group included 58 eyes of 58 patients newly diagnosed with primary Sjögren syndrome with poor dry eye test findings and the control group included 45 right eyes of 45 healthy age- and sex-matched individuals. The ocular surface disease index score, tear osmolarity, Schirmer I test without anesthesia, fluorescein tear breakup time, and cornea-conjunctiva staining with lissamine green (van Bijsterveld scoring) were used to examine tear function in the patients via a complete ophthalmological examination. The results were graded and classified on the basis of a Dry Eye WorkShop report and results of the corneal and conjunctival staining test, Schirmer's test, and fluorescein tear breakup time test. Discomfort, severity and frequency of symptoms, visual symptoms, conjunctival injection, eyelid-meibomian gland findings, and corneal-tear signs were interpreted. Disease activity was scored per the EULAR Sjögren's syndrome disease activity index (ESSDAI) via systemic examination and laboratory evaluations, and the EULAR Sjögren's syndrome patient-reported index (ESSPRI) assessed via a survey of patient responses. Results: Mean patient age was 48.15 ± 16.34 years in the primary Sjögren syndrome group and 44.06 ± 9.15 years in the control group. Mean fluorescein tear breakup time was 4.51 ± 2.89s in the primary Sjögren syndrome group and 10.20 ± 2.39 s in the control group. Mean Schirmer I test result was 3.51 ± 3.18 mm/5 min in the primary Sjögren syndrome group and 9.77±2.30 mm/5 min in the control group. Mean ocular surface disease index score was 18.56 ± 16.09 in the primary Sjögren syndrome group, and 19.92 ± 7.16 in the control group. Mean osmolarity was 306.48 ± 19.35 in the primary Sjögren syndrome group, and 292.54 ± 10.67 in the control group. Mean lissamine green staining score was 2.17 ± 2.76 in the primary Sjögren syndrome group, and 0.00 in the control group. Statistically significant differences were found berween the primary Sjögren syndrome group and control group in terms of fluorescein tear breakup time, Schirmer's test, lissamine green staining, and osmolarity tests (p=0.036, p=0.041, p=0.001, and p=0.001 respectively). The Dry Eye WorkShop score was 2.15 ± 0.98, the EULAR Sjögren's syndrome disease activity index score was 11.18 ± 4.05, and the EULAR Sjögren's syndrome patient-reported index score was 5.20±2.63. When potential associations of the Dry Eye Workshop Study scores and osmolarity scores with the Eular Sjögren's syndrome disease activity index scores were evaluated, the results were found to be statistically significant (p=0.001, p=0.001 respectively). Conclusion: The results showed an association between dry eye severity and systemic activity index in primary Sjögren syndrome patients.

RESUMO Objetivo: O objetivo do presente estudo foi comparar a gravidade dos achados oculares e sistêmicos entre pacientes com síndrome de Sjögren primária. Métodos: O estudo seguiu um delineamento prospectivo controlado e compreendeu dois grupos; o grupo de teste incluiu 58 olhos de 58 pacientes recém-diagnosticados com síndrome de Sjögren primária com resultados deficientes no teste de olho seco e o grupo controle incluiu 45 olhos direitos de 45 indivíduos saudáveis pareados idade e sexo. A contagem do índice de doença da superfície ocular, osmolaridade lacrimal, teste de Schirmer I sem anestesia, tempo de ruptura da fluoresceína e coloração córnea-conjuntiva com verde de lissamina (índice de van Bijsterveld) foram utilizados para examinar a função lacrimal dos pacientes através de exame oftalmológico completo. Os resultados foram classificados com base em um relatório da "Dry Eye Workshop" e resultados do teste de coloração da córnea e conjuntiva, teste de Schirmer e teste do tempo de ruptura da fluoresceína. Desconforto, gravidade e frequência dos sintomas, sintomas visuais, injeção conjuntival, achados das glândulas palpebrais e sinais da córnea foram interpretados. A atividade da doença foi avaliada pelo índice de atividade da doença da síndrome de Sjögren EULAR por meio de exame sistêmico e avaliações laboratoriais, e o índice relatado pelo paciente da síndrome de Sjörgen EULAR avaliado através de uma pesquisa das respostas dos pacientes. Resultados: A média de idade dos pacientes foi de 48,15 ± 16,34 anos no grupo da Síndrome de Sjörgen primária e 44,06 ± 9,15 anos no grupo controle. O tempo médio de ruptura da fluoresceína foi de 4,51 ± 2,89 s no grupo síndrome de Sjögren primária e 10,20 ± 2,39 s no grupo controle. O resultado do teste de Schirmer I médio foi de 3,51 ± 3,18 mm/5 min no grupo síndrome de Sjögren primária e de 9,77 ± 2,30 mm/5 min no grupo controle. O índice médio de doença da superfície ocular foi de 18,56 ± 16,09 no grupo síndrome de Sjögren primária e 19,92 ± 7,16 no grupo controle. A osmolaridade média foi 306,48 ± 19,35 no grupo síndrome de Sjögren primária e 292,54 ± 10,67 no grupo controle. O resultado médio de coloração com lissamina verde foi de 2,17 ± 2,76 no grupo síndrome de Sjögren primária e 0,00 no grupo controle. Diferenças es­tatisticamente significativas foram encontradas entre o com sín­­drome de Sjögren primária e o grupo controle em termos de tempo de ruptura da fluoresceína lacrimal, teste de Schirmer I, coloração com lissamina verde e osmolaridade (p=0,036, p=0,041, p=0,001, p=0,001 respectivamente). O índice Estudo do Olho Seco foi de 2,15 ± 0,98, o índice de atividade da doença da síndrome de Sjögren EULAR foi de 11,18 ± 4,05 e a pontuação do índice relatado pelo paciente EULAR Sjögren foi de 5,20 ± 2,63. Quando associações potenciais do Estudo do Olho Seco e o índice da osmolaridade foram comparados a pontuação de índice de atividade da doença da síndrome de Sjögren EULAR, os resultados foram estatisticamente significantes (p=0,001, p=0,001 respectivamente). Conclusão: Os resultados mostraram uma associação entre a gravidade do olho seco e o índice de atividade sistêmica em pacientes com síndrome de Sjögren primária.

Nuclear parameters and chromatin remodeling in epithelial cells and lymphocytes from the palpebral conjunctiva of dogs with keratoconjunctivitis sicca.

OBJECTIVE: To study parameters related to nuclear morphology and chromatin remodeling in epithelial cells and lymphocytes from the inferior palpebral conjunctiva of dogs with and without keratoconjunctivitis sicca (KCS). ANIMALS STUDIED: Thirty-two dogs (64 eyes) were included in the study. Based on the tear production measured by Schirmer tear test 1, the dogs were distributed into control and KCS groups. PROCEDURES: Epithelial cells and lymphocytes were collected by conjunctival brush cytology, fixed on glass slides, and subjected to the Feulgen reaction, a topochemical method specific for DNA/chromatin. Feulgen-stained cells were studied by microscopy and video image analysis to establish nuclear size (area and perimeter) and shape (relative nuclear roundness factor = RNRF), DNA content (ploidy), and compaction and texture of chromatin. RESULTS: Conjunctival samples in the KCS group showed infiltration of inflammatory and immune cells. Micronuclei, snake-like chromatin, aberrant chromosomes, and goblet cells were not detected. Compared with the controls, cells on the conjunctival surface of dogs with KCS showed altered nuclei. Conjunctival epithelial cells were more affected by KCS (changes in nuclear size, shape, DNA content, and chromatin compaction) than lymphocytes (changes in chromatin compaction, only). Significant chromatin decompaction was observed in both conjunctival epithelial cells and lymphocytes. CONCLUSIONS: Our results show that KCS promotes chromatin remodeling in epithelial cells and lymphocytes on the conjunctival surface of dogs. The changes described in this study are different from those reported for conjunctival cell nuclei of human KCS patients.

Surgical Factors Affecting Changes in Ocular Surface Dynamics in the Early Postoperative Period After 25-Gauge Vitrectomy.

OBJECTIVES: Because vitrectomy-associated postoperative ocular surface changes are not well known, we evaluated such changes before and after vitrectomy in eyes with posterior segment diseases and investigated their associations with patients' characteristics and surgical procedures. METHODS: Thirty-five eyes of 32 consecutive patients (16 women; average age 66.6±11.1 years) were included in this prospective, noncomparative case series from tertiary care university hospital. Contact lens wearers and patients with history of ocular surgery or regular use of topical eyedrops were excluded. Patients had undergone primary 25-gauge vitrectomy at Osaka University Hospital in Japan between July and December 2016. Tear break-up time (TBUT), corneal and conjunctival fluorescein staining score (FSS), and tear meniscus height (TMH) were evaluated before, 1 week after, and 1 month after vitrectomy. RESULTS: Conjunctival FSS and TMH were significantly higher at 1 week after vitrectomy than preoperatively. However, they decreased significantly 1 month after. Changes in TBUT and corneal FSS showed a similar course at 1 week, but this was not statistically significant. Multiple linear regression analysis showed no significant correlation between significantly increased ocular parameters and patients' characteristics. By contrast, surgical time and combined cataract surgery significantly contributed to increased and decreased conjunctival FSS, respectively (P=0.011 and 0.033, respectively). Sclerotomy site suturing significantly contributed to increased TMH (P=0.025). CONCLUSIONS: We showed associations between ocular surface changes and specific surgical procedures. Caution should be exercised to minimize the effect of surgical procedures on the ocular surface during vitrectomy.

Association between systemic activity index and dry eye severity in patients with primary Sjögren syndrome.

PURPOSE: The aim of the present study was to compare the severity of ocular and systemic findings among patients with primary Sjögren syndrome. METHODS: The study followed a prospective controlled design and comprised two groups; the test group included 58 eyes of 58 patients newly diagnosed with primary Sjögren syndrome with poor dry eye test findings and the control group included 45 right eyes of 45 healthy age- and sex-matched individuals. The ocular surface disease index score, tear osmolarity, Schirmer I test without anesthesia, fluorescein tear breakup time, and cornea-conjunctiva staining with lissamine green (van Bijsterveld scoring) were used to examine tear function in the patients via a complete ophthalmological examination. The results were graded and classified on the basis of a Dry Eye WorkShop report and results of the corneal and conjunctival staining test, Schirmer's test, and fluorescein tear breakup time test. Discomfort, severity and frequency of symptoms, visual symptoms, conjunctival injection, eyelid-meibomian gland findings, and corneal-tear signs were interpreted. Disease activity was scored per the EULAR Sjögren's syndrome disease activity index (ESSDAI) via systemic examination and laboratory evaluations, and the EULAR Sjögren's syndrome patient-reported index (ESSPRI) assessed via a survey of patient responses. RESULTS: Mean patient age was 48.15 ± 16.34 years in the primary Sjögren syndrome group and 44.06 ± 9.15 years in the control group. Mean fluorescein tear breakup time was 4.51 ± 2.89s in the primary Sjögren syndrome group and 10.20 ± 2.39 s in the control group. Mean Schirmer I test result was 3.51 ± 3.18 mm/5 min in the primary Sjögren syndrome group and 9.77±2.30 mm/5 min in the control group. Mean ocular surface disease index score was 18.56 ± 16.09 in the primary Sjögren syndrome group, and 19.92 ± 7.16 in the control group. Mean osmolarity was 306.48 ± 19.35 in the primary Sjögren syndrome group, and 292.54 ± 10.67 in the control group. Mean lissamine green staining score was 2.17 ± 2.76 in the primary Sjögren syndrome group, and 0.00 in the control group. Statistically significant differences were found berween the primary Sjögren syndrome group and control group in terms of fluorescein tear breakup time, Schirmer's test, lissamine green staining, and osmolarity tests (p=0.036, p=0.041, p=0.001, and p=0.001 respectively). The Dry Eye WorkShop score was 2.15 ± 0.98, the EULAR Sjögren's syndrome disease activity index score was 11.18 ± 4.05, and the EULAR Sjögren's syndrome patient-reported index score was 5.20±2.63. When potential associations of the Dry Eye Workshop Study scores and osmolarity scores with the Eular Sjögren's syndrome disease activity index scores were evaluated, the results were found to be statistically significant (p=0.001, p=0.001 respectively). CONCLUSION: The results showed an association between dry eye severity and systemic activity index in primary Sjögren syndrome patients.