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1.
Transl Vis Sci Technol ; 12(6): 8, 2023 06 01.
Article En | MEDLINE | ID: mdl-37310735

Purpose: The purpose of this study was to determine if there are significant differences in the concentrations of tear proteins in Sjögren's syndrome keratoconjunctivitis sicca (SS KCS) compared to healthy controls. Methods: Tear samples were collected with unmarked Schirmer strips from 15 patients with SS KCS and 21 healthy controls. Tear protein was eluted and the concentration measured. Inflammatory mediators were assayed with a Raybiotech L-507 glass slide array and normalized by strip wetting length. All patients underwent an ocular surface exam to evaluate tear break-up time (TBUT), corneal fluorescein (CF) staining, and conjunctival (CJ) staining. The symptom assessment questionnaire in dry eye (SANDE) scores were collected for all patients. Results: Two hundred fifty-three of the 507 tear proteins analyzed were significantly different in patients with SS compared to controls. Two hundred forty-one if the proteins were upregulated and 12 were downregulated. One hundred eighty-one differentially expressed proteins were significantly correlated with all four clinical parameters: TBUT, CF staining, CJ staining, and SANDE score. Conclusions: These findings indicate that hundreds of factors can be assayed in tear proteins collected from a Schirmer strip. The results suggest tear protein concentrations are altered in patients with SS KCS compared to controls. The upregulated tear proteins correlated with clinical measures of dry eye symptoms and disease severity. Translational Relevance: Tear proteins could serve as important biomarkers for studying pathogenesis and in clinical diagnosis and management of SS KCS.


Dry Eye Syndromes , Keratoconjunctivitis Sicca , Sjogren's Syndrome , Humans , Keratoconjunctivitis Sicca/diagnosis , Sjogren's Syndrome/diagnosis , Dry Eye Syndromes/diagnosis , Conjunctiva , Fluorescein
2.
J Vet Sci ; 24(2): e32, 2023 Mar.
Article En | MEDLINE | ID: mdl-37012039

BACKGROUND: The association between vitamin D and canine keratoconjunctivitis sicca (KCS) has not been investigated in dogs. OBJECTIVES: To investigate the association of serum 25-hydroxyvitamin D [25(OH)D] concentrations with Schirmer tear test 1 (STT-1) and tear film breakup time (TFBUT) in dogs. METHODS: Sixty-one clinically healthy, client-owned dogs were enrolled. STT-1 and TFBUT were measured in 122 (61dogs) and 82 (41 dogs out of total 61 dogs) eyes, respectively. Serum 25(OH)D concentrations were evaluated by quantitative chemiluminescent immunoassay. The dogs were classified into 6 groups according to the evaluations (STT-1: group 1, normal [≥ 15 mm/min] in both eyes; group 2, normal in one eye and abnormal [< 15 mm/min] in the fellow eye; group 3, abnormal in both eyes; TFBUT: group 4, normal [≥ 20 sec] in both eyes; group 5, normal in one eye and abnormal [< 20 sec] in the fellow eye; group 6, abnormal in both eyes). RESULTS: STT-1 was positively correlated with TFBUT (p < 0.001). Among the STT-1 groups, the mean serum 25(OH)D concentration in group 1 was significantly higher than in groups 2 and 3 with positive correlation (p < 0.001). However, there were no significant differences among the TFBUT groups 4, 5, and 6. CONCLUSIONS: In dogs, it was found that serum 25(OH)D concentrations had a greater effect on quantitative KCS than qualitative KCS. Therefore, it is considered that measurement of serum 25(OH)D concentration could be included in the diagnostic tests in canine quantitative KCS patients.


Dog Diseases , Keratoconjunctivitis Sicca , Dogs , Animals , Keratoconjunctivitis Sicca/diagnosis , Keratoconjunctivitis Sicca/veterinary , Eye , Dog Diseases/diagnosis , Vitamin D
3.
Vet Ophthalmol ; 26 Suppl 1: 5-15, 2023 Apr.
Article En | MEDLINE | ID: mdl-36575128

Dry eye disease (DED) is a complex multifactorial condition caused by loss of ocular surface homeostasis from quantitative and/or qualitative tear film deficiency. Schirmer tear test (STT) is often the only diagnostic test used to assess for DED in veterinary practice. STT is invaluable in the diagnosis and monitoring of quantitative tear film deficiency (i.e., keratoconjunctivitis sicca); however, it is not sufficient to optimize therapy and fully recognize other contributing factors for the disturbance in ocular surface homeostasis. The present work reviews diagnostic tests for assessing aqueous tear production in veterinary medicine, as well as the quality of tears, corneal epithelial barrier integrity, and the lacrimal functional unit.


Dry Eye Syndromes , Keratoconjunctivitis Sicca , Dogs , Animals , Dry Eye Syndromes/diagnosis , Dry Eye Syndromes/veterinary , Keratoconjunctivitis Sicca/diagnosis , Keratoconjunctivitis Sicca/veterinary , Cornea , Tears , Diagnostic Tests, Routine
4.
Curr Opin Ophthalmol ; 33(6): 551-556, 2022 Nov 01.
Article En | MEDLINE | ID: mdl-36165413

PURPOSE OF REVIEW: This article summarizes the pathophysiology of rheumatoid arthritis and common ocular manifestations that it is associated with: keratoconjunctivitis sicca, episcleritis, scleritis, and peripheral ulcerative keratitis. RECENT FINDINGS: Newer biologic agents are being used to effectively treat rheumatoid arthritis and its ocular manifestations. SUMMARY: The eye is a frequent extra-articular site of inflammation in patients with rheumatoid arthritis. Ocular involvement can range from more benign conditions such as keratoconjunctivitis sicca and episcleritis, to potentially vision and globe-threatening diseases like scleritis and peripheral ulcerative keratitis. Clinicians should be aware of these ophthalmic manifestations and the various treatment options that are available. Coordination between ophthalmology and rheumatology is helpful in the treatment of these patients.


Arthritis, Rheumatoid , Corneal Ulcer , Keratoconjunctivitis Sicca , Scleritis , Arthritis, Rheumatoid/complications , Biological Factors , Corneal Ulcer/diagnosis , Corneal Ulcer/drug therapy , Corneal Ulcer/etiology , Humans , Keratoconjunctivitis Sicca/diagnosis , Keratoconjunctivitis Sicca/etiology , Scleritis/diagnosis , Scleritis/drug therapy , Scleritis/etiology
5.
Vet Ophthalmol ; 25(2): 140-152, 2022 Mar.
Article En | MEDLINE | ID: mdl-34870366

OBJECTIVE: To describe the clinical findings, imaging features, underlying conditions, treatment, and progression of dogs presented between 2010 and 2019 with neurogenic keratoconjunctivitis sicca (NKCS). METHODS: Dogs diagnosed with NKCS were searched in the clinical database. Inclusion criteria were STT-1 readings <15 mm/min, clinical signs of KCS with concurrent ipsilateral xeromycteria. RESULTS: Thirty-four cases were identified. Mean age at presentation was 8.2 years, median 8.9 years (0.3-14.7). Twenty dogs were male, and 14 dogs were female. Concurrent neurological deficits included facial neuropathy (n = 13, 38%), peripheral vestibular syndrome (n = 10, 29%), and Horner's syndrome (n = 5, 15%). Advanced imaging was acquired in 53% of cases (n = 18). Etiologies included idiopathic (n = 18, 53%), endocrinopathy (n = 6, 18%), otitis interna (n = 4, 12%), head trauma (n = 3, 9%), iatrogenic (post-TECA-LBO, n = 1, 3%), brainstem mass (n = 1, 3%), and an area of inflammation in the pterygopalatine fossa (n = 1, 3%). Treatment for NKCS was initiated in most cases (n = 30, 88%) including: oral pilocarpine 2% and lacrimostimulant (n = 19), oral pilocarpine 2% only (n = 3), or lacrimostimulant only (n = 8). A mean time follow-up of 3.7 months, median 3 months (1-14) was available in 23 cases (68%). Eleven cases with follow-up were responsive (48%) with resolution of the clinical signs in a median time 4 months (1-10), and all of them were treated with oral pilocarpine (±lacrimostimulant). CONCLUSIONS: Most cases presented as idiopathic NKCS; in others, an underlying cause of facial neuropathy was identified. All responsive cases were treated with oral pilocarpine 2%.


Dog Diseases , Horner Syndrome , Keratoconjunctivitis Sicca , Animals , Dog Diseases/diagnosis , Dog Diseases/drug therapy , Dog Diseases/etiology , Dogs , Female , Horner Syndrome/veterinary , Keratoconjunctivitis Sicca/diagnosis , Keratoconjunctivitis Sicca/drug therapy , Keratoconjunctivitis Sicca/veterinary , Male , Pilocarpine/therapeutic use
6.
Vet Ophthalmol ; 25(3): 219-224, 2022 May.
Article En | MEDLINE | ID: mdl-34929058

OBJECTIVE: To establish tear film osmolarity (TFO) values in Pugs and Shih-Tzus, with and without keratoconjunctivitis sicca (KCS). ANIMALS STUDIED: A total of 82 adult dogs were evaluated. PROCEDURE: The inclusion criteria for the healthy group was a Schirmer tear test (STT-1) ≥15 mm/min with no clinical signs of KCS, whereas those with KCS had clinical signs and a STT-1 ≤10 mm/min. All animals underwent complete ophthalmological evaluation prior to STT-1 and TFO. Student's t tests were used to compare STT-1 and TFO in KCS and healthy eyes as well as possible differences in TFO between breeds. In addition, a linear regression to model the relationship between the two variables (STT-1 and TFO) was performed. A P-value ≤ 0.05 was considered statistically significant. RESULTS: STT-1 results were significantly lower (p = 0.0001) in the KCS group (4.46 ± 1.74) compared with the control group (18.80 ± 2.02). Mean TFO results were significantly higher in the KCS group (353.02 ± 16.58 mOsm/L) (p < 0.0001) compared with the control group (315.27 ± 6.15 mOsm/L). The formula Y = 365.059-2.625 * X significantly predicts (p < 0.001) the value of the variable Y (TFO mOsm/L) as a function of the variable X (STT-1 mm/min), with a coefficient of determination of 0.71. CONCLUSIONS: The results revealed differences in TFO and STT-1 between KCS and healthy dogs. Additionally, STT-1 and TFO values were correlated with the aim to use STT-1 values to predict TFO values in brachycephalic breeds.


Dog Diseases , Dry Eye Syndromes , Keratoconjunctivitis Sicca , Lacerations , Animals , Dog Diseases/diagnosis , Dogs , Dry Eye Syndromes/veterinary , Humans , Keratoconjunctivitis Sicca/diagnosis , Keratoconjunctivitis Sicca/veterinary , Lacerations/veterinary , Osmolar Concentration , Tears
7.
J Ocul Pharmacol Ther ; 37(7): 394-398, 2021 09.
Article En | MEDLINE | ID: mdl-34232790

Purpose: To determine the effect of discontinuing chronic topical immune modulating (IM) treatment on Schirmer tear test (STT) values in dogs with dry eye disease (DED). Methods: Serial measurements of STTs from 14 dogs (16 eyes) previously diagnosed with DED were obtained before and after discontinuation of topical IM agents. Dogs with moderate to severe DED that had been well controlled with a topical IM treatment were included. After initial assessment topical IM treatment was discontinued, but topical lubricant was continued, and STT values were obtained sequentially. A mixed-effects regression model was used to evaluate the effects of age, gender, breed, clinical score, frequency of treatment, baseline STT value, and drug type on final STT values after IM withdrawal. P < 0.05 was considered statistically significant. Results: During the follow-up period after the IM treatment had been discontinued (136 ± 29 days), 50% of the eyes (n = 8) exhibited STT values that never decreased to <10 mm/min. In the other 50% (n = 8), STT values decreased from 15.9 ± 4.7 mm/min to 6.1 ± 0.9 mm/min. In this group, the time it took to decrease the STT to <10 mm/min was 21.1 ± 9.5 days. Severe clinical signs of DED and low baseline STT pre-IM treatment significantly affected STT post-IM treatment withdrawal (P < 0.05). Conclusions: The duration that a residual effect of topical IM treatment persists needs to be taken into consideration when studies are designed utilizing dogs with previous IM treatment for DED.


Dog Diseases/immunology , Dry Eye Syndromes/immunology , Keratoconjunctivitis Sicca/immunology , Tears/immunology , Administration, Topical , Animals , Dog Diseases/diagnosis , Dog Diseases/drug therapy , Dogs , Dry Eye Syndromes/diagnosis , Dry Eye Syndromes/drug therapy , Keratoconjunctivitis Sicca/diagnosis , Keratoconjunctivitis Sicca/drug therapy , Male , Ophthalmic Solutions/administration & dosage , Ophthalmic Solutions/pharmacology , Tears/drug effects
8.
Ocul Immunol Inflamm ; 29(4): 796-802, 2021 May 19.
Article En | MEDLINE | ID: mdl-33830848

The purpose of this review is to delve into the clinical and research understanding of the pathophysiology and presentation of Sjögren's-related keratoconjunctivitis sicca in order address the diagnostic and management challenge that it represents, as well as to provide a basis for appreciating the pharmacotherapies designed to treat the ophthalmic symptoms of Sjögren's disease.


Sjogren's Syndrome/physiopathology , Dry Eye Syndromes/diagnosis , Dry Eye Syndromes/physiopathology , Humans , Keratoconjunctivitis Sicca/diagnosis , Keratoconjunctivitis Sicca/physiopathology , Meibomian Glands/physiopathology , Sjogren's Syndrome/diagnosis , Tears/physiology
9.
Rheumatology (Oxford) ; 60(12): 5647-5658, 2021 12 01.
Article En | MEDLINE | ID: mdl-33620072

OBJECTIVE: To assess the potential diagnostic utility of advanced lymphocyte profiling to differentiate between primary Sjögren's Syndrome (pSS) and non-Sjögren Sicca syndrome. METHODS: Distribution of peripheral lymphocyte subpopulations was analysed by flow cytometry in 68 patients with pSS, 26 patients with sicca syndrome and 23 healthy controls. The ability to discriminate between pSS and sicca syndrome was analysed using the area under the curve (AUC) of the receiver operating characteristic curve of the different lymphocyte subsets. RESULTS: The ratio between naïve/memory B cell proportions showed an AUC of 0.742 to differentiate pSS and sicca syndrome, with a sensitivity of 76.6% and a specificity of 72% for a cut-off value of 3.4. The ratio of non-switched memory B cells to activated CD4+ T cells percentage (BNSM/CD4ACT) presented the highest AUC (0.840) with a sensitivity of 83.3% and specificity of 81.7% for a cut-off value <4.1. To differentiate seronegative pSS patients from sicca patients, the BNSM/CD4ACT ratio exhibited an AUC of 0.742 (sensitivity 75%, specificity 66.7%, cut-off value <4.4), and the number of naïve CD4 T cells had an AUC of 0.821 (sensitivity 76.9%, specificity 88.9%, cut-off value <312/mm3). CONCLUSION: Patients with pSS show a profound imbalance in the distribution of circulating T and B lymphocyte subsets. The ratio BNSM/CD4ACT is useful to discriminate between pSS and sicca syndrome.


Keratoconjunctivitis Sicca/diagnosis , Lymphocyte Subsets/pathology , Sjogren's Syndrome/diagnosis , Adult , Aged , Diagnosis, Differential , Female , Flow Cytometry , Follow-Up Studies , Humans , Keratoconjunctivitis Sicca/immunology , Lymphocyte Subsets/immunology , Male , Middle Aged , ROC Curve , Retrospective Studies , Sjogren's Syndrome/immunology
10.
Curr Eye Res ; 46(1): 23-30, 2021 01.
Article En | MEDLINE | ID: mdl-32506959

AIM OF THE STUDY: Hidradenitis suppurativa (HS) and psoriasis vulgaris (PSO) are chronic inflammatory dermatoses in which proinflammatory cytokines, such as IL-17, play a central role. The prevalence of keratoconjunctivitis sicca (KCS) is commonly higher in PSO than in healthy individuals. This study was thus set up to investigate the prevalence of KCS among patients with HS. MATERIALS AND METHODS: In a cross-sectional study standardized tear film parameters and symptom-oriented questionnaires (OSDI, SPEED) were analyzed in a total of 71 subjects (HS n = 20, PSO n = 20, healthy controls n = 31). Additionally, IL-17 and MMP-9 in the tear film were analyzed. These parameters were correlated to the clinical severity of the skin disease. PSO patients served as inflammatory control group. RESULTS: There were statistically significant differences in OSDI (p = .003) and SPEED (p ≤ 0.001) between HS and the control group, but not between PSO and controls. For HS, there was a statistically significant correlation between symptoms (OSDI) and the severity of HS according to Hurley stage (p = .023). Tear film concentrations showed significantly increased levels of IL-17 (p = .018), but not MMP-9, in PSO alone compared to the control group. CONCLUSION: Data show that subjective complaints of KCS may be associated with HS and correlate with the severity of the respective Hurley stage, but do not involve alterations of tear film MMP-9 and IL-17. Clinicians should remain mindful that ocular complications in HS are often more vague than in psoriatic patients, but dry eye symptoms might be detrimental for the patients' quality of life.


Hidradenitis Suppurativa/diagnosis , Keratoconjunctivitis Sicca/diagnosis , Adolescent , Adult , Aged , Cross-Sectional Studies , Enzyme-Linked Immunosorbent Assay , Female , Hidradenitis Suppurativa/epidemiology , Humans , Interleukin-17/metabolism , Keratoconjunctivitis Sicca/epidemiology , Male , Matrix Metalloproteinase 9/metabolism , Middle Aged , Osmolar Concentration , Prevalence , Prospective Studies , Quality of Life , Surveys and Questionnaires , Tears/metabolism , Young Adult
11.
Ocul Immunol Inflamm ; 29(2): 250-256, 2021 Feb 17.
Article En | MEDLINE | ID: mdl-32293936

Purpose: To report the clinical profile of genetically proven Blau syndrome in seven cases from a single center in South India.Materials & Methods: Retrospective case seriesResults: There were four females and three males. All cases had a history of skin and joint involvement of varying severity. Flexion contractures of the proximal interphalangeal joints were seen in all cases except Case 2. Ocular involvement was bilateral and included keratoconjunctivitis sicca (six cases), granulomatous panuveitis (three cases), granulomatous anterior uveitis (three cases), conjunctival granulomas (three cases), subepithelial corneal opacities (one case), and subretinal granuloma (one case). Other ocular findings included band-shaped keratopathy (five cases) and cataract (three cases). All cases received oral steroids and methotrexate with an addition of mycophenolate mofetil in one case. Visual prognosis was good in all cases.Conclusions: Blau syndrome is underreported in India. This is the largest case series of genetically proven Blau syndrome from South India and highlights the clinical profile of Blau syndrome seen in India.


Arthritis/genetics , Conjunctiva/diagnostic imaging , Cornea/diagnostic imaging , Keratoconjunctivitis Sicca/etiology , Mutation , Nod2 Signaling Adaptor Protein/genetics , Sarcoidosis/genetics , Synovitis/genetics , Uveitis/genetics , Visual Acuity , Arthritis/complications , Arthritis/diagnosis , Child , Child, Preschool , DNA/genetics , DNA Mutational Analysis , Female , Humans , India , Keratoconjunctivitis Sicca/diagnosis , Keratoconjunctivitis Sicca/physiopathology , Male , Nod2 Signaling Adaptor Protein/metabolism , Retrospective Studies , Sarcoidosis/complications , Sarcoidosis/diagnosis , Slit Lamp Microscopy , Synovitis/complications , Synovitis/diagnosis , Uveitis/complications , Uveitis/diagnosis
12.
Eur J Ophthalmol ; 31(2): 328-333, 2021 Mar.
Article En | MEDLINE | ID: mdl-32064919

PURPOSE: To analyse the occurrence and cost of dry eye disease in Spain in the recent years. METHODS: A cross-sectional analysis based on anonymised data from an insurance claims database that includes data from 1997 to 2015 from public and private hospitals and healthcare centres; 36,081 patients were eligible for the study after duplicate elimination. Five ICD9 codes associated with dry eye were used for patient selection, including vitamin A deficiency with xerophthalmic scars of cornea, xerophthalmia due to vitamin A deficiency, keratoconjunctivitis sicca not specified as Sjögren's, dry eye syndrome and keratoconjunctivitis sicca Sjögren's disease. RESULTS: Over 88% of the patients were female, and the mean age was 66 years. Patients with keratoconjunctivitis sicca Sjögren's disease represented more than 89% of all patients and had the highest percentage of women. Both the annual number of patients and the number of admissions have increased exponentially since 1997 raising from 1079 to 3097 and from 1344 to 5938, respectively. The in-hospital length of stay was 9.6 (standard deviation = 11.6) days where more than 65% of the admissions were due to emergencies. Total costs were found to increase from €4.9 to €30.3 million during the study period; in parallel, there was an increase in the mean annual cost per patient, which was on average €7379. CONCLUSION: Disease incidence is likely to increase due to the influence of modern-day workplace, and it is important to take into account the high economic burden and the large decrease in quality of life in regards to Spanish society and health policies.


Dry Eye Syndromes/economics , Aged , Aged, 80 and over , Cost of Illness , Cross-Sectional Studies , Databases, Factual , Delivery of Health Care/economics , Dry Eye Syndromes/diagnosis , Female , Health Care Costs/trends , Hospitalization/economics , Humans , Insurance Claim Review/economics , Keratoconjunctivitis Sicca/diagnosis , Keratoconjunctivitis Sicca/economics , Male , Middle Aged , Quality of Life , Retrospective Studies , Sjogren's Syndrome/diagnosis , Sjogren's Syndrome/economics , Spain/epidemiology , Xerophthalmia/diagnosis , Xerophthalmia/economics
13.
Cornea ; 39(8): 1013-1016, 2020 Aug.
Article En | MEDLINE | ID: mdl-32251167

PURPOSE: To evaluate the ocular signs and tests for keratoconjunctivitis sicca (KCS) in the absence of a gold standard. METHODS: Cross-sectional study of participants from the Sjögren's International Collaborative Clinical Alliance (SICCA) registry. Participants had oral/ocular/rheumatologic examinations, blood/saliva samples collected, and salivary gland biopsy. Latent class analysis (LCA) identified clusters of patients based on 3 to 4 predictor variables relating to signs or tests of KCS. The resulting model-based "gold standard" classification formed the basis for estimated sensitivity and specificity associated with these predictors. RESULTS: A total of 3514 participants were enrolled into SICCA, with 52.9% classified as SS. LCA revealed a best-fit model with 2 groups. For the gold standard-positive group, an abnormal tear breakup time, ocular staining score (OSS), and Schirmer I had a sensitivity of 99.5%, 91.0%, and 47.4%, respectively. For the gold standard-negative group, an abnormal tear breakup time, OSS, and Schirmer I had a specificity of 32.0%, 84.0%, and 88.5%, respectively. OSS components (fluorescein and lissamine staining), exhibited a sensitivity of 82.6% and 90.5%, respectively, in the gold standard-positive group, whereas these signs in the gold standard-negative group had a specificity of 88.8% and 73.0%, respectively. CONCLUSIONS: OSS and its components (fluorescein and lissamine staining) differentiated 2 groups from each other better than other KCS parameters and had relatively high sensitivity and specificity.


Conjunctiva/pathology , Keratoconjunctivitis Sicca/diagnosis , Registries , Tears/metabolism , Cross-Sectional Studies , Female , Humans , Keratoconjunctivitis Sicca/metabolism , Male , Young Adult
14.
Ocul Immunol Inflamm ; 28(6): 854-859, 2020 Aug 17.
Article En | MEDLINE | ID: mdl-31013173

PURPOSE: To report the clinical features, severity, and management of ocular immune-related adverse events (irAEs) in the setting of immune checkpoint inhibitor therapy for metastatic malignancies. METHODS: Retrospective chart review at three tertiary ophthalmology clinics. Electronic medical records were reviewed between 2000 and 2017 for patients with new ocular symptoms while undergoing checkpoint inhibition therapy. RESULTS: Eleven patients were identified. Ocular irAEs ranged from keratoconjunctivitis sicca to Vogt-Koyanagi-Harada-like findings. Average timing of irAEs from starting checkpoint inhibitor therapy was 15.7 weeks. Ocular inflammation was successfully controlled with corticosteroids in most cases, however three patients discontinue treatment as a result of ocular inflammation with decreased visual acuity, two discontinued due to progression of metastatic disease, and one discontinued due to severe systemic irAEs. CONCLUSION: We found a wide spectrum of ocular irAEs associated with immune checkpoint inhibitors. In most cases, ocular AEs did not limit ongoing cancer treatment.


Immune Checkpoint Inhibitors/adverse effects , Keratoconjunctivitis Sicca/chemically induced , Neoplasms/drug therapy , Optic Nerve Diseases/chemically induced , Uveitis/chemically induced , Uveomeningoencephalitic Syndrome/chemically induced , Adult , Aged , Female , Humans , Ipilimumab/adverse effects , Keratoconjunctivitis Sicca/diagnosis , Male , Middle Aged , Nivolumab/adverse effects , Optic Nerve Diseases/diagnosis , Retrospective Studies , Uveitis/diagnosis , Uveomeningoencephalitic Syndrome/diagnosis
15.
BMJ Case Rep ; 12(8)2019 Aug 28.
Article En | MEDLINE | ID: mdl-31466972

A 47-year-old woman presented with sicca symptoms, polyarthralgias, polymyalgias and dysphagia. She was found to have positive antinuclear, anti-SSA-Ro and anti-SSB-La antibodies. Slit lamp exam confirmed the presence of keratoconjunctivitis sicca, and the patient was diagnosed with Sjögren's syndrome. Three years later, she was referred for evaluation of gait instability associated with recent falls. On physical examination, the patient was found to have bilateral ptosis, percussion myotonia, distal upper and lower extremity weakness, and a steppage gait. Electromyography demonstrated electrical myotonia. Genetic testing revealed expanded CTG repeats (733 and 533) in the myotonic dystrophy type 1 (DM1) protein kinase gene, confirming the diagnosis of DM1. Dysphagia, pain and eye discomfort may occur in both Sjögren's syndrome and DM1, and in this case, may have delayed the diagnosis of muscular dystrophy.


Myotonic Dystrophy/etiology , Myotonic Dystrophy/genetics , Sjogren's Syndrome/complications , Antibodies, Antinuclear/immunology , Cyclosporine/administration & dosage , Cyclosporine/therapeutic use , Diagnosis, Differential , Electromyography/methods , Female , Humans , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/therapeutic use , Keratoconjunctivitis Sicca/diagnosis , Keratoconjunctivitis Sicca/drug therapy , Middle Aged , Myotonic Dystrophy/physiopathology , Myotonic Dystrophy/therapy , Myotonin-Protein Kinase , Protein Kinases/genetics , Sjogren's Syndrome/blood , Treatment Outcome
16.
Cornea ; 38(12): 1568-1575, 2019 Dec.
Article En | MEDLINE | ID: mdl-31369464

PURPOSE: To perform a comprehensive clinical, diagnostic, and imaging characterization of the ocular surface in West Highland White Terriers (WHWTs) diagnosed with aqueous deficient dry eye (ADDE) disease. METHODS: Six ADDE-affected and 13 ADDE-unaffected WHWT dogs were enrolled and underwent clinical assessment and disease scoring, tear osmolarity, phenol red thread test, Schirmer tear test, tear film breakup time, fluorescein staining, Rose bengal and lissamine green vital dye staining, meibometry, corneal esthesiometry, ultrasound pachymetry, optical coherence tomography, in vivo confocal microscopy, and conjunctival biopsy. Subjective assessment of their condition was provided by owner-reported surveys. RESULTS: ADDE-affected WHWT dogs had higher median clinical disease (conjunctiva: 5.75 vs. 0.00; cornea: 14.00 vs. 5.00; total: 17.50 vs. 5.00), vital staining (Rose bengal: 2.25 vs. 1.50; lissamine green: 2.00 vs. 1.00), and histologic disease (conjunctiva: 2 vs. 0) scores when compared with the controls. In addition, ADDE-affected WHWTs had significantly lower phenol red thread test (5.0 vs. 17.5, mm/15 s), Schirmer tear test (3 vs. 20, mm/min), tear film breakup time (3.6 vs. 13.9, s) values and higher area under the curve values for meibometry (394 vs. 245, meibometry units [MU]). There were no significant differences in other tear film tests performed. Advanced imaging revealed decreased tear meniscus height (optical coherence tomography) and variable pigment deposition within corneal epithelial cells (in vivo confocal microscopy). CONCLUSIONS: This comprehensive assessment of ADDE-affected WHWTs depicts the ocular surface changes associated with quantitative lacrimal gland dysfunction. Importantly, ADDE-affected WHWTs may prove a valuable naturally occurring ADDE model for investigating underlying pathophysiological mechanisms and the development of novel therapeutics.


Aqueous Humor/metabolism , Dog Diseases/diagnosis , Dry Eye Syndromes/veterinary , Keratoconjunctivitis Sicca/veterinary , Animals , Coloring Agents/metabolism , Cornea/metabolism , Corneal Pachymetry/veterinary , Dog Diseases/metabolism , Dogs , Dry Eye Syndromes/diagnosis , Dry Eye Syndromes/metabolism , Female , Fluorescein/metabolism , Fluorescent Dyes/metabolism , Keratoconjunctivitis Sicca/diagnosis , Keratoconjunctivitis Sicca/metabolism , Lissamine Green Dyes/administration & dosage , Male , Meibomian Glands/metabolism , Osmolar Concentration , Rose Bengal/administration & dosage , Slit Lamp Microscopy/veterinary , Tears/chemistry , Tears/physiology , Tomography, Optical Coherence/veterinary
17.
Cornea ; 38(10): 1259-1265, 2019 Oct.
Article En | MEDLINE | ID: mdl-31306284

BACKGROUND: Keratoconjunctivitis sicca affects 5% to 33% of the population and is often accompanied by symptoms such as burning and dryness. This pooled analysis evaluated total and central corneal fluorescein staining (CFS) in patients receiving OTX-101 0.09% or vehicle in phase 2b/3 and 3 studies and whether improvements in corneal staining correlated with improved visual acuity. METHODS: In these randomized, vehicle-controlled studies, patients received 1 drop of OTX-101 or vehicle in both eyes twice daily. Corneal staining was performed at baseline and days 28, 56, and 84. CFS was evaluated in each zone (0-to-4 scale); total corneal staining (0-to-20 scale per eye) was averaged over both eyes. Pooled safety assessments included adverse event monitoring. RESULTS: Mean baseline CFS total scores (SD) were 4.2 (2.5) and 4.3 (2.6) for the OTX-101 (n = 523) and vehicle (n = 525) groups, respectively. For total corneal staining, least squares mean changes from baseline (standard error) were -0.9 (0.08) versus -0.5 (0.08) for OTX-101 and vehicle, respectively (P = 0.0008), on day 28 and -1.4 (0.09) versus -0.9 (0.09) on day 84 (P = 0.0002). There was a significantly high correlation (P = 0.0117) between reduced central corneal staining and improved visual acuity on day 84. Treatment-related adverse events were mostly mild, with instillation site pain reported by 21.8% and 4.0% of patients receiving OTX-101 and vehicle, respectively. CONCLUSIONS: Treatment with OTX-101 led to greater improvements versus vehicle in corneal surface staining as early as 4 weeks, and further improvements were seen up to 12 weeks. OTX-101 was well tolerated in patients with keratoconjunctivitis sicca.


Cornea/pathology , Cyclosporine/administration & dosage , Keratoconjunctivitis Sicca/drug therapy , Visual Acuity , Cornea/drug effects , Dose-Response Relationship, Drug , Double-Blind Method , Female , Humans , Immunosuppressive Agents/administration & dosage , Keratoconjunctivitis Sicca/diagnosis , Male , Micelles , Middle Aged , Ophthalmic Solutions/administration & dosage , Ophthalmoscopy , Staining and Labeling , Treatment Outcome
18.
Acta Med Port ; 32(4): 260-265, 2019 Apr 30.
Article En | MEDLINE | ID: mdl-31067419

INTRODUCTION: Given the increasing use of electronic devices, and the increasing number of complaints with its use, we intend to evaluate the prevalence of manifestations of dry eye and ocular fatigue in a population of individuals, who use the computer daily to perform all their professional tasks, as well as to correlate these complaints with the number of hours of digital use as well as their possible improvement with behavioural measures and use of tear drops. MATERIAL AND METHODS: A total of 77 individuals (154 eyes) were evaluated on two separate days with a 1-month interval. They completed two questionnaires: OSDI and PEG Eye Fatigue. An objective ocular surface assessment was performed: Schirmer test without anesthetic, DR-1a Dry Eye Monitor™, hyperemia evaluation, lacrimal break up, presence of keratitis and lesions in the conjunctiva, as well as near accommodation point and near convergence point. After the first evaluation, the subjects were divided into two groups: group A (< 2 hours of computer working) and group B (> 2 hours of computer working). Some environmental measures to reduce complaints and recommendation of use of artificial tears were explained to the latter. RESULTS: There was a statistically significant difference in the majority of the parameters evaluated in the group B, in relation to the morning period (group A) - tear film (p = 0.032), hyperemia (p < 0.001), BUT (p < 0.001), keratitis (p < 0.001), conjunctival lesion (p = 0.002) and accommodation point (p < 0.001). In the evaluation - one month later - there were no statistically significant differences in any of the parameters analysed in the group A, and in group B there was a decrease in most parameters at the end of that period - Schirmer test (p = 0.005), lacrimal film (p = 0.022), keratitis (p < 0.001), conjunctival lesion (p = 0.005) and fatigue score (p < 0.001). DISCUSSION: It was thus possible to show the appearance of ocular fatigue and ocular surface changes with prolonged use of computers (> 2 hours) as well as a significant improvement in symptomatology (subjective assessment) as well as of ocular surface changes (objective evaluation) with the implementation of postural measures, regular breaks and use of lubricants. This is the first study, to the best of our knowledge, of digital asthenopia in which, in addition to the subjective evaluation, the presence of ocular surface modifications (objective assessment) were evaluated and the respective improvement with the aforementioned ergophthalmological measures were evaluated. CONCLUSION: This survey highlights the increased overall level of awareness that we need to have to face the rapid and wide-scale changes driven by the emergence of digital technology and, more particularly, its impact on user's vision and posture. We concluded that the longer we use the electronic devices (more than two hours) the more severe the complaints and rates of ocular surface changes are. Environmental and ocular strategies can attenuate or even eliminate the discomfort caused by this syndrome, and increase professional performance and quality of life.


Introdução: Atendendo ao uso crescente dos dispositivos eletrônicos, e o consequente aumento de queixas oftalmológicas com o seu uso, pretendemos com este estudo avaliar a prevalência de manifestações de olho seco e fadiga ocular numa população de indivíduos, de uma empresa de 'outsourcing services' e que utilizam o computador diariamente para realizar todas as suas tarefas. Material e Métodos: Um total de 77 indivíduos (154 olhos) foram avaliados em dois dias separados por um intervalo de um mês. Completaram dois questionários: OSDI e GPE Fadiga Ocular. Foi realizada uma avaliação objetiva da superfície ocular: teste de Schirmer sem anestesia, DR-1a Dry Eye Monitor™, avaliação hiperémia, rotura lacrimal, presença de queratite e lesões da conjuntiva, bem como avaliação do ponto próximo de acomodação e ponto próximo de convergência. Após a primeira avaliação, dividiu-se a amostra em dois grupos: grupo A (< 2 horas de trabalho no computador) e grupo B (> 2 horas de trabalho no computador). Ao grupo B foram explicadas algumas medidas ambientais para reduzir as queixas de astenopia digital e recomendou-se uso de lágrima artificial de acordo com as necessidades. Resultados: Observou-se uma diferença estatisticamente significante na maioria dos parâmetros avaliados no grupo B, quando comparado com o grupo no período da manhã (grupo A) - filme lacrimal (p = 0,032), hiperémia (p < 0,001), BUT (p < 0,001), queratite (p < 0,001), lesões da conjuntiva (p = 0,002) e ponto próximo de acomodação (p < 0,001). Na avaliaçã o - um mês depois - não houveram diferenças estatisticamente significativas em nenhum dos parâmetros analisados no grupo A, enquanto que no grupo B houve redução na maioria dos parâmetros ao final desse período - teste de Schirmer (p = 0,005), filme lacrimal (p = 0,022), queratite (p < 0,001), lesões da conjuntiva (p = 0,005), ponto de convergência próximo (p = 0,001) e score de fadiga (p < 0,001). Discussão: Foi assim possível objetivar o aparecimento de fadiga ocular e alterações da superfície ocular com o uso prolongado de computadores (> 2 horas) bem como uma melhoria significativa da sintomatologia (avaliação subjetiva) e melhoria da superfície ocular (avaliação objetiva) com a implementação de medidas posturais, pausas regulares e uso de lubrificantes. Este é o primeiro estudo, tanto quanto temos conhecimento, de astenopia digital em que para além da avaliação subjetiva se avalia a presença das referidas alterações da superfície ocular e a sua melhoria com as medidas ergoftalmológicas mencionadas. Conclusão: Este estudo realça a necessidade de estarmos alerta para as constantes e rápidas mudanças relacionadas com o uso crescente dos diferentes dispositivos digitais, bem como com o seu impacto oftalmológico e postural. Concluímos desta forma que quanto mais tempo usamos os dispositivos eletrónicos (> 2 horas), maiores são a probabilidade de desenvolver queixas e alterações da superfície ocular. As estratégias ambientais e oculares podem atenuar ou até mesmo eliminar o desconforto causado por esta síndrome e melhorar a qualidade de vida e o desempenho profissional.


Asthenopia/epidemiology , Computer Terminals/statistics & numerical data , Dry Eye Syndromes/epidemiology , Adaptation, Ocular , Adult , Conjunctival Diseases/diagnosis , Dry Eye Syndromes/complications , Female , Health Surveys , Humans , Hyperemia/diagnosis , Keratoconjunctivitis Sicca/diagnosis , Male , Portugal/epidemiology , Tears , Time Factors
19.
Vet Rec ; 184(22): 678, 2019 06 01.
Article En | MEDLINE | ID: mdl-31019006

OBJECTIVE: Determine morphological and morphometric parameters of corneal epithelium in dogs, and determine the cellular alterations that occur in canine keratoconjunctivitis sicca (KCS) using impression cytology. STUDY ANIMALS: 60 dogs divided into two groups: dogs with Schirmer tear test (STT) at least 15 mm/minute and absence of ocular disease, and dogs with STT less than 15 mm/minute and clinical signs of KCS. PROCEDURES: Impression cytology was used to collect corneal samples. The percentage of eyes with cell changes, the number of such cells and the percentage of cells with structural alterations in each group were determined. The possible correlation between corneal epithelium alterations and decreased tear production was evaluated. RESULTS: A significant positive correlation existed between STT and the area of the cytoplasm and nucleus of corneal cells. A significant negative correlation was found between STT ​​and the nucleus/cytoplasm ratio, and the presence of cellular changes. A significant difference existed between the numbers of pyknotic nuclei, being higher among animals with all stages of KCS. CONCLUSION: Corneal impression cytology can be used to assess the corneal epithelium in healthy eyes and eyes with KCS, demonstrating its usefulness as a diagnostic tool especially in mild and early cases.


Cornea/cytology , Dog Diseases/diagnosis , Keratoconjunctivitis Sicca/veterinary , Animals , Dogs , Keratoconjunctivitis Sicca/diagnosis
20.
Scand J Rheumatol ; 48(3): 198-206, 2019 May.
Article En | MEDLINE | ID: mdl-30475093

OBJECTIVE: The aim was to investigate prevalence and degree of ocular and oral involvement in patients with primary Sjögren's syndrome (PSS). METHOD: We analysed 134 participants from the Korean Initiative of PSS cohort who completed a 2 year follow-up oral and ocular sign test. The severity of keratoconjunctivitis sicca (KCS) was determined with the Schirmer I test value (STV) [abnormal (AB) ≤ 5 mm/5 min; normal (N) > 5 mm/5 min]. Salivary gland dysfunction (SGD) was determined by unstimulated whole salivary (UWS) flow rate [moderate to severe (MS) < 0.1 mL/min; mild (Mi) ≥ 0.1 mL/min]. Subgroups were divided into three groups according to STV and severity of SGD: AB-STV/MS-SGD, AB-STV/Mi-SGD, and N-STV/MS-SGD groups. We analysed the changes in STV and SGD during the follow-up period. RESULTS: Among the 134 participants enrolled in this study, 105 (78%) were placed in the AB-STV/MS-SGD group, 16 (12%) in the AB-STV/Mi-SGD, and 13 (10%) in the N-STV/MS-SGD at the 2 year follow-up. The AB-STV/Mi-SGD group was younger than the other two groups, and had a lower Xerostomia Inventory score and lower level of ß2-microglobulin. Participants in the N-STV/MS-SGD group had less hyperimmunoglobulinaemia, rheumatoid factor (RF), and antinuclear antibodies (ANAs). Patients and those with positive RF or ANA ≥ 1:320 at baseline were more likely to have abnormal STV at the 2 year follow-up. CONCLUSIONS: Patients with PSS and positive RF or ANA ≥ 1:320 at baseline may benefit from regular ophthalmology examinations, even if they do not have KCS at baseline or dry eye symptoms.


Keratoconjunctivitis Sicca , Sjogren's Syndrome/complications , Xerostomia , Adult , Age Factors , Antibodies, Antinuclear/blood , Cohort Studies , Female , Humans , Keratoconjunctivitis Sicca/diagnosis , Keratoconjunctivitis Sicca/etiology , Keratoconjunctivitis Sicca/immunology , Male , Middle Aged , Prevalence , Republic of Korea/epidemiology , Rheumatoid Factor/blood , Severity of Illness Index , Sjogren's Syndrome/diagnosis , Sjogren's Syndrome/epidemiology , Symptom Assessment , Xerostomia/diagnosis , Xerostomia/etiology , Xerostomia/immunology
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