The International Workshop on Meibomian Gland Dysfunction: Report of the Clinical Trials Subcommittee

Diagnostic tests of meibomian gland dysfunction (MGD) and of MGD-related disorders are based on the demonstration of abnormal anatomy and physiology of the glands and the detection of specific pathologic events. For this reason, this subcommittee report is divided into two sections. In part I, those aspects of meibomian anatomy and physiology that are relevant to currently available tests are described; a fuller account of the anatomy and physiology is provided in the report of the Anatomy Subcommittee of this workshop. In part II, each test and its performance is described in detail. In part III, the practical application of selected tests is summarized and recommendations for future approaches are made. Additional recommendations and a summary of pertinent literature and concepts are presented in Appendices 1 to 17

The International Workshop on Meibomian Gland Dysfunction: Report of the Clinical Trials Subcommittee

Recently it has been demonstrated that a compressed monolayer of palmitoyl-(R)-lysine (Fig. 1) on the surface of water induces the orientated growth of α-glyeine crystals$^1$. This effect was inter-preted to be a structural match between the monolayer and the α-glycine. To test this hypothesis we undertook to determine the packing arrangement of the monolayer by grazing incidence X-ray diffraction and reflection. These techniques$^2$ use the unique proper-ties of synchrotron radiation: high intensity within a small natural collimation$^3$. In the diffraction experiment two peaks were detect-able in the two-dimensional powder pattern from a monolayer of palmitoyl-(R)-lysine. The positions and intensities of these peaks allowed us to choose between various models and determine the monolayer structure. This is the first time that the crystal structure of a compressed surfactant monolayer at the air–water interface has been determined. The same techniques could be used for structural characterization of other monolayers of interest in fields as diverse as biological membranes4 and optical second harmonic generation5. The packing arrangement of the α-amino acid head groups in the model proved to be very similar to that found in the crystal structures of α-glycine and several hydrophobic α-amino acids

Renal Transplant Patients Biopsied for Cause and Tested for C4d, DSA, and IgG Subclasses and C1q: Which Humoral Markers Improve Diagnosis and Outcomes?

The association between donor specific antibodies (DSA) and renal transplant rejection has been generally established, but there are cases when a DSA is present without rejection. We examined 73 renal transplant recipients biopsied for transplant dysfunction with DSA test results available: 23 patients diffusely positive for C4d (C4d+), 25 patients focally positive for C4d, and 25 patients negative for C4d (C4d−). We performed C1q and IgG subclass testing in our DSA+ and C4d+ patient group. Graft outcomes were determined for the C4d+ group. All 23 C4d+ patients had IgG DSA with an average of 12,500 MFI (cumulative DSA MFI). The C4d− patients had average DSA less than 500 MFI. Among the patients with C4d+ biopsies, 100% had IgG DSA, 70% had C1q+ DSA, and 83% had complement fixing IgG subclass antibodies. Interestingly, IgG4 was seen in 10 of the 23 recipients’ sera, but always along with complement fixing IgG1, and we have previously seen excellent function in patients when IgG4 DSA exists alone. Cumulative DSA above 10,000 MFI were associated with C4d deposition and complement fixation. There was no significant correlation between graft loss and C1q positivity, and IgG subclass analysis seemed to be a better correlate for complement fixing antibodies in the C4d+ patient group

An objective approach to dry eye disease severity. Invest Ophthalmol Vis Sci

PURPOSE. A prospective, multisite clinical study (10 sites in the European Union and the United States) evaluated the clinical utility of commonly used tests and tear osmolarity for assessing dry eye disease severity. METHODS. Three hundred fourteen consecutive subjects between the ages of 18 and 82 years were recruited from the general patient population, 299 of which qualified with complete datasets. Osmolarity testing, Schirmer test without anesthesia, tear film breakup time (TBUT), corneal staining, meibomian dysfunction assessment, and conjunctival staining were performed bilaterally. A symptom questionnaire, the Ocular Surface Disease Index (OSDI), was also administered to each patient. Distributions of clinical signs and symptoms against a continuous composite severity index were evaluated. RESULTS. Osmolarity was found to have the highest correlation coefficient to disease severity (r 2 ϭ 0.55), followed by conjunctival staining (r 2 ϭ 0.47), corneal staining (r 2 ϭ 0.43), OSDI (r 2 ϭ 0.41), meibomian score (r 2 ϭ 0.37), TBUT (r 2 ϭ 0.30), and Schirmer result (r 2 ϭ 0.17). A comparison of standard threshold-based classification with the composite severity index revealed significant overlap between the disease severities of prospectively defined normal and dry eye groups. Fully 63% of the subjects were found to be poorly classified by combinations of clinical thresholds. CONCLUSIONS. Tear film osmolarity was found to be the single best marker of disease severity across normal, mild/moderate, and severe categories. Other tests were found to be informative in the more severe forms of disease; thus, clinical judgment remains an important element in the clinical assessment of dry eye severity. The results also indicate that the initiation and progression of dry eye is multifactorial and supports the rationale for redefining severity on the basis of a continuum of clinical signs. (ClinicalTrials.gov number, NCT00848198.) (Invest Ophthalmol Vis Sci. 2010;51:6125-6130