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Purpose: To determine the intra-observer and inter-observer reliability of a novel ocular staining score among trained ophthalmologists., Design: Reliability analysis within a prospective, observational, multicenter cohort study., Methods: Those enrolled in the National Institutes of Health-funded Sjögren's International Collaborative Clinical Alliance (SICCA) who presented for follow-up at the University of California San Francisco, Aravind Eye Hospital, Johns Hopkins University, and the University of Pennsylvania were included. Study participants were graded using the ocular staining score by at least 2 masked SICCA-trained ophthalmologists. The primary outcome for this study was the intraclass correlation coefficient (ICC) for the total ocular staining score. ICCs were also calculated for tear break-up time (TBUT) and conjunctival and corneal staining., Results: Total ocular staining score had an ICC of 0.91 for the right eye (95% confidence interval [CI] 0.85-0.96) and 0.90 for the left eye (95% CI 0.83-0.97). Corneal staining (right eye 0.86, 95% CI 0.76-0.93, left eye 0.90, 95% CI 0.81-0.95) and conjunctival staining (right eye 0.87, 95% CI 0.80-0.93, left eye 0.85, 95% CI 0.75-0.93) demonstrated excellent agreement. The ICC for TBUT was slightly lower (right eye 0.77, 95% CI 0.64-0.89; left eye 0.81, 95% CI 0.68-0.90)., Conclusions: Previous studies have shown that the ocular staining score is correlated with other diagnostic components of Sjögren syndrome. In this study, we demonstrate high reliability in grading among trained ophthalmologists, completing the validation of this test., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Importance: Knowledge about the variability of measurements using the TearLab Osmolarity System is necessary when evaluating the clinical utility of readings., Objective: To examine the variability of tear osmolarity measured by the TearLab Osmolarity System in patients with Sjögren syndrome (SS), patients with blepharitis, and control participants., Design, Setting, and Participants: Cross-sectional study at a tertiary care academic center from June 13, 2012, to March 21, 2013. Participants included 74 eyes of 37 patients from a volunteer sample (18 patients with SS, 11 patients with blepharitis, and 8 control participants) who were evaluated using the TearLab Osmolarity System, with 3 consecutive osmolarity measurements taken at 1-minute intervals in a session; 15 of these patients had the same measurements taken by the same examiner in 2 additional sessions on the same day (9 AM-10 AM, 12 PM-1 PM, or 3 PM-4 PM). Most patients with SS and patients with blepharitis were taking systemic or topical dry eye medications at the time of enrollment., Main Outcomes and Measures: Mean osmolarity and its variability calculated from a linear mixed model for each disease group that accounts for the variations attributable to different patients, eyes, and sessions and measurement error specific to each disease group., Results: Mean tear osmolarity was 307 mOsm/L, 304 mOsm/L, and 301 mOsm/L in the SS, blepharitis, and control groups, respectively (P = .46). The error associated with repeated measurements within a session in the patients without dry eye (10.5 mOsm/L [95% CI, 9.0-12.4]) was significantly lower than in the patients with blepharitis (14.6 mOsm/L [95% CI, 12.5-17.5]; P = .006) and patients with SS (15.8 mOsm/L [95% CI, 14.2-17.8]; P < .001) but a difference in the error of repeated measurements between patients with blepharitis and patients with SS was not identified (P = .46)., Conclusions and Relevance: There was increased variability attributable to error in repeated measurements in patients with SS and patients with blepharitis compared with control participants. The high variability of TearLab osmolarity readings in all groups makes the clinical interpretation of measurements unclear.

Purpose: To describe a standardized technique for acquiring and viewing photographic images of eyelids, assess the reproducibility and validity of a grading protocol for signs of anterior blepharitis, and to explore whether the signs depend on the eyelid or the area of the eyelid assessed., Methods: Subjects with anterior blepharitis ranging from none to severe were examined by ophthalmologists at clinical sites. Digital images of the eyelids of subjects were acquired using a protocol that allowed for the calibration of color and luminance. Three ophthalmologists at a centralized reading center applied a novel protocol for grading features of anterior blepharitis from the digital images viewed on color-calibrated monitors. The agreement among graders was assessed using percent agreement and weighted kappa statistics (Kw), and the correlation of photographic and clinical gradings was assessed using Spearman correlation coefficients., Results: Agreement among graders was excellent (Kw > 0.80) on the number of eyelid margin vessels and was substantial (Kw between 0.61 and 0.80) for erythema, collarettes, number of engorged vessels, and number of lashes. Grading of the photographic images and the clinical assessments of erythema and lid debris were moderately correlated (r = 0.27-0.45). The grades for different features depended on whether the upper or lower eyelid, eyelid skin or lid margin, and central or lateral lid were assessed., Conclusions: The application of a protocol to obtain and display calibrated digital images of eyelids supports the standardized assessment of anterior blepharitis in clinical care and research studies.

Purpose: The Schirmer test is one of the 2 ocular surface tests included in the current classification criteria for Sjögren syndrome (SS). Tear osmolarity may also be a useful test for the diagnosis of dry eye disease. The purpose of this study was to examine the relationship between tear osmolarity, the Schirmer test I, and dry eye symptoms in SS., Methods: Patients with a diagnosis of SS were assessed for tear osmolarity with the TearLab Osmolarity System, tear production with Schirmer testing, symptoms with the Ocular Surface Disease Index (OSDI), and discomfort associated with each test., Results: Forty-nine patients with a mean age of 53.7 years and a female (92%) predominance were enrolled. The majority of patients (86%) were receiving systemic therapy for severe SS. Higher tear osmolarity was moderately associated with lower scores on the Schirmer test I (ρ = -0.39, P < 0.01) and OSDI (ρ = -0.45, P < 0.01). Schirmer test I results and lower OSDI scores were not correlated significantly (ρ = 0.20, P = 0.17). Tear osmolarity testing was significantly less painful than Schirmer testing (P < 0.01)., Conclusions: Signs and symptoms of dry eye in SS patients were not strongly correlated. An unexpected finding was that higher tear osmolarity was associated with lower symptom severity. Tear osmolarity testing in the clinical setting was feasible and was associated with significantly less discomfort than Schirmer testing in patients with severe SS.

Purpose: The aim of this study was to examine the relationship among oral contraceptive pill (OCP) use, contact lens wear, and dry eye signs and symptoms in healthy young women., Methods: Fifty-two women using OCPs and 45 women not using any form of hormonal contraception were enrolled. Medical, menstrual, and contact lens histories were obtained and dry eye symptoms assessed using the Ocular Surface Disease Index (OSDI) and Symptom Assessment iN Dry Eye (SANDE) questionnaires. Tear osmolarity testing was performed using the TearLab Osmolarity System., Results: The mean age of all subjects was 26.0 ± 3.7 years. There were no significant differences in any of the measurements between the follicular and luteal phases. Although SANDE scores were significantly higher in subjects with OCP and recent contact lens use (P < 0.01), there were no significant differences in OSDI and tear osmolarity among the same subject groups. Subjects who reported both OCP and recent contact lens use had significantly higher OSDI and SANDE scores (P = 0.015 and P < 0.001, respectively)., Conclusions: There were no differences between the phases of the menstrual cycle. Tear osmolarity was not affected by OCP or contact lens use in young women. However, the combination of OCP use and contact lens wear may increase the severity of dry eye symptoms.

Purpose: To describe a patient with resolution of cornea verticillata while still using amiodarone as a result of a drug interaction lowering serum levels of amiodarone., Methods: An 83-year-old retired physician with long-standing cornea verticillata was noted to have complete resolution of cornea verticillata on a routine follow-up eye examination. The patient reported complete compliance with using amiodarone daily, with no recent changes in dosage or formulation. Despite this, he reported a recent increase in the frequency of palpitations. He had recently started rifampin for treatment of tuberculosis., Results: Serum amiodarone and desethylamiodarone levels were obtained and found to be below therapeutic range. After rifampin was discontinued, serum amiodarone and desethylamiodarone levels increased to a therapeutic range and cornea verticillata returned after 4 months., Conclusions: In patients currently using amiodarone, clearing of cornea verticillata should alert the ophthalmologists to the possibility of decreased serum amiodarone levels.

Elevated intraocular pressure-induced interlamellar stromal keratitis (PISK) is an entity of interface haze usually occurring weeks to months after laser in situ keratomileusis (LASIK) that is associated with elevated intraocular pressures and worsening with steroid treatment. There is evidence that this interface haze is the result of abnormal fluid dynamics that occur in the cornea after LASIK. We present a case of pressure-induced interlamellar stromal keratitis occurring 9 years after LASIK in the setting of anterior uveitis. This case emphasizes the importance of considering such diagnoses as pressure-induced interlamellar stromal keratitis in the differential diagnosis when presented with a patient with corneal haze and a history of LASIK.

Purpose: To report 2 cases of corneal edema, haze, and thinning in patients after undergoing selective laser trabeculopasty., Methods: Selective laser trabeculoplasty was performed for the treatment of primary open-angle glaucoma on 2 patients who subsequently developed corneal stromal haze within 24 to 48 hours of the procedure., Results: The patients were treated with topical steroids for several weeks. Although their corneal edema resolved, both patients were left with residual corneal scarring and thinning. One patient had a significant hyperopic shift., Conclusions: Corneal edema, haze, and thinning after selective laser trabeculoplasty is an extremely rare event, with only 2 other cases reported in the literature. Although certain causes are postulated to play a role in this complication, it is not yet understood what may predispose a patient to corneal changes as a result of this laser procedure.

Purpose: To report a case of presumed bilateral corneal copper deposition secondary to oral contraceptive use., Methods: A 23-year-old woman was referred for evaluation of bilateral corneal opacities. The location of the deposits deep in Descemet's membrane and appearance made copper deposition a likely consideration., Results: Subsequent laboratory results revealed an elevated serum copper level (189 μg/dL). Other causes of cupremia were subsequently ruled out, and the patient's corneal copper deposition was attributed to her oral contraceptive use. With cessation of the oral contraceptive, her serum copper levels normalized, but the corneal deposits remained after 5 months of follow up., Conclusion: To our knowledge, we report the first case in the ophthalmic literature of presumed corneal copper deposition in the setting of oral contraceptive use. It is important to recognize the corneal findings associated with copper deposition, because it may lead to the diagnosis and treatment of other serious systemic conditions causing elevated serum copper levels.

Purpose: To describe nine patients with fungal keratitis refractory to standard antifungal therapy whose condition was managed with voriconazole., Design: Retrospective case series., Methods: Chart review of patients with fungal keratitis who were treated with topical and oral voriconazole., Results: Nine patients were treated. Two patients were contact lens wearers who used multipurpose cleaning solutions. Corneal isolates found were Fusarium (three patients), Candida albicans (three patients), Alternaria (one patient), Scopulariopsis (one patient), and Scedosporium apiospermum (one patient). Nine patients were treated with topical voriconazole, and eight patients were treated with oral voriconazole. Patients were treated topically for four to 16 weeks (mean, 10 weeks) and orally for five to 17 weeks (mean, 10 weeks). One patient was lost to follow-up. Two patients discontinued the topical voriconazole after one day and four weeks, respectively, because of ocular burning. Of the seven patients who were treated with topical therapy and followed, five conditions healed., Conclusion: Voriconazole is a new, promising therapy for fungal keratitis that is refractory to standard antifungal treatments.

Purpose: To evaluate cardiovascular risk factors and events in glaucoma patients with and without peripapillary focal arteriolar narrowing of retinal vessels., Methods: We examined the fundus photographs of 325 consecutive glaucoma patients for evidence of focal arteriolar narrowing of retinal vessels adjacent to the optic disc. Cases and controls were matched for age, race, sex and mean deviation on Humphrey visual field. Medical information regarding cardiovascular risk factors and events was collected from patients' primary care physicians, and this information was confirmed by questionnaires sent to the patients themselves., Results: A total of 58 pairs of cases and controls were matched. The prevalence of hypertension and diabetes was exactly equal in both groups, 65.5% and 27.6%, respectively. Similarly, the prevalences of myocardial infarction, cardiac surgery, angioplasty, family history of heart disease and smoking were nearly identical in both groups. There was no significant difference in the prevalence of strokes or transient ischaemic attacks. The prevalence of hypercholesterolemia and mortality was greater in the case group (mean differences of 8.6, p = 0.42 and 5.2, p = 0.25, respectively), however, these differences were not statistically significant., Conclusion: There is no significant relationship between peripapillary focal arteriolar narrowing of retinal vessels and cardiovascular risk factors or events in patients with glaucoma. Proximal narrowing does not appear to be a marker of systemic vascular disease.

A method is described for the isolation of filamentous phage-displayed human monoclonal antibodies directed at unpurifiable cell surface-expressed molecules. To optimize the capture of antigen-specific phage and minimize the binding of irrelevant phage antibodies, a simultaneous positive and negative selection strategy is employed. Cells bearing the antigen of interest are pre-coated with magnetic beads and diluted into an excess of unmodified antigen-negative cells. Following incubation of the cell admixture with a Fab/phage library, the antigen-positive cell population is retrieved using magnetically-activated cell sorting and antigen-specific Fab/phage are eluted and propagated in bacterial culture. Utilizing this protocol with magnetically-labeled Rh(D)-positive and excess unlabeled Rh(D)-negative human red blood cells and a Fab/phage library constructed from human peripheral blood lymphocytes, dozens of unique clinically-useful gamma 1 kappa and gamma 1 lambda anti-Rh(D) antibodies were isolated from a single alloimmunized individual. This cell-surface selection method is readily adaptable for use in other systems, such as for the identification of putative tumor-specific antigens and provides a rapid (< 1 month), high-yield approach for isolating self-replicative antibody reagents directed at novel or conformationally-dependent cell-surface epitopes.