Lifitegrast clinical efficacy for treatment of signs and symptoms of dry eye disease across three randomized controlled trials

Objective: Report efficacy findings from three clinical trials (one phase 2 and two phase 3 [OPUS-1, OPUS-2]) of lifitegrast ophthalmic solution 5.0% for treatment of dry eye disease (DED).

Research design and methods: Three 84-day, randomized, double-masked, placebo-controlled trials. Adults (≥18 years) with DED were randomized (1:1) to lifitegrast 5.0% or matching placebo. Changes from baseline to day 84 in signs and symptoms of DED were analyzed.

Main outcome measures: Phase 2, pre-specified endpoint: inferior corneal staining score (ICSS; 0–4); OPUS-1, coprimary endpoints: ICSS and visual-related function subscale (0–4 scale); OPUS-2, coprimary endpoints: ICSS and eye dryness score (EDS, VAS; 0–100).

Results: Fifty-eight participants were randomized to lifitegrast 5.0% and 58 to placebo in the phase 2 trial; 293 to lifitegrast and 295 to placebo in OPUS-1; 358 to lifitegrast and 360 to placebo in OPUS-2. In participants with mild-to-moderate baseline DED symptomatology, lifitegrast improved ICSS versus placebo in the phase 2 study (treatment effect, 0.35; 95% CI, 0.05–0.65; p?=?0.0209) and OPUS-1 (effect, 0.24; 95% CI, 0.10–0.38; p?=?0.0007). Among more symptomatic participants (baseline EDS ≥40, recent artificial tear use), lifitegrast improved EDS versus placebo in a post hoc analysis of OPUS-1 (effect, 13.34; 95% CI, 2.35–24.33; nominal p?=?0.0178) and in OPUS-2 (effect, 12.61; 95% CI, 8.51–16.70; p?<?0.0001).

Limitations: Trials were conducted over 12 weeks; efficacy beyond this period was not assessed.

Conclusions: Across three trials, lifitegrast improved ICSS in participants with mild-to-moderate baseline symptomatology in two studies, and EDS in participants with moderate-to-severe baseline symptomatology in two studies. Based on the overall findings from these trials, lifitegrast shows promise as a new treatment option for signs and symptoms of DED.     

Production of herpes B virus recombinant glycoproteins and evaluation of their diagnostic potential

B virus (cercopithecine herpesvirus 1) is the only deadly alphaherpesvirus that is zoonotically transmissible from macaques to humans. The detection of humoral immune responses is the method of choice for the rapid identification of B virus-infected animals. We evaluated the diagnostic potential of recombinant B virus glycoproteins for the detection of immunoglobulin G (IgG) antibodies in monkey and human sera. Glycoproteins B, C, and E and secreted (sgG) and membrane-associated (mgG) segments of glycoprotein G (gG) were expressed in the baculovirus expression system, while gD was expressed in CHO cells. We developed recombinant protein-based IgG enzyme-linked immunosorbent assays (ELISAs) and compared their diagnostic efficacies by using B virus antibody-negative (n = 40) and -positive (n = 75) macaque sera identified by a whole antigen-based ELISA and Western blotting. The diagnostic sensitivities of the gB-, gC-, gD-, and mgG-ELISAs were 100, 97.3, 88.0, and 80.0%, respectively. The specificities of the gB-, gC-, and gD-ELISAs and of the mgG-ELISA were 100 and 97.5%, respectively. In contrast, the sensitivities and specificities of sgG- and gE-ELISAs were low, suggesting that sgG and gE are less effective diagnostic antigens. Sera from nonmacaque monkeys cross-reacted with gB, gC, and gD, and only baboon sera reacted weakly with mgG. Human herpes simplex virus type 1 (HSV-1)- and HSV-2-positive sera pools reacted with gB and gD, whereas sera from B virus-infected individuals reacted with all four antigens. These data indicate that gB, gC, gD, and mgG have a high diagnostic potential for B virus serodiagnosis in macaques, whereas mgG may be a valuable antigen for discrimination between antibodies induced by B virus and those induced by other, closely related alphaherpesviruses, including HSV-1 and -2.     

Bovine Herpesvirus-1 Glycoprotein M Mediates the Translocation to the Golgi Apparatus and Packaging of VP8

VP8, the most abundant tegument protein of bovine herpesvirus-1 (BoHV-1), plays an important role in viral replication. According to our previous studies, VP8 localizes to the Golgi apparatus of BoHV-1-infected cells where it can be packaged into the virus; however, Golgi localization of VP8 does not occur outside of the context of infection. The goal of this study was to identify the viral factor(s) involved in the tropism of VP8 towards the Golgi. VP8 was found to interact with glycoprotein M (gM), and the VP8 and gM domains that are essential for this interaction were identified. VP8 and gM colocalized to the Golgi apparatus in BoHV-1-infected cells. In cells co-transfected with VP8- and gM-encoding plasmids, VP8 was also found to be localized to the Golgi, suggesting gM to be sufficient. The localization of VP8 to the Golgi was lost in cells infected with a gM deletion mutant, and the amount of VP8 incorporated into mature virus was significantly reduced. However, with the restoration of gM in a revertant virus, the localization to the Golgi and the amount of VP8 incorporated in the virions were restored. These results indicate that gM plays a critical role in VP8 subcellular localization to the Golgi and packaging into mature virions.     

Should Silicone Lacrimal Stenting be a Better Choice for Primary Endoscopic Powered Dacryocystorhinostomy?

Objective: To compare endoscopic dacryocystorhinostomy (EnDCR) with and without silicone lacrimal stenting through subjective (patients’) and objective (surgeons’) outcome parameters. Methodology: Following defined selection criteria, EnDCR was performed on patients with primary chronic dacryocystitis with post-saccal stenosis. Every alternate patient had silicone lacrimal stenting (group A: no stenting; group B: with stenting); stents were removed at three months. At six months (minimum follow-up period), patients’ responses on symptom relief (through a five-point score) and naso-endoscopic evaluation (visualization of rhinostome; presence of granulations and synechiae; lacrimal drainage patency by estimating methylene blue flow pattern) were compared between the groups. Results: Each group had 20 patients. There was no statistically significant difference in group-wise follow-up periods. Five-point score at six months revealed 85% and 95% of patients in groups A and B, respectively, experienced “success”; among them, 60% and 75% were “symptom-free”. The majority (75%) in group B experienced no discomfort from stenting. Naso-endoscopy revealed 80% patients in group A and 65% in group B had well-delineated rhinostome, albeit with granulations in 25% and 50%, respectively. Spontaneous dye flow was achieved, respectively, in 75% and 90%. The difference in none of the subjective and endoscopic parameters achieved statistical significance. None had synechia; fibrosis was seen in the four patients with no dye flow even with pressure/massaging. Conclusion: There was no statistically significant difference in EnDCR with and without silicone lacrimal stenting in the overall outcome of symptomatic improvement and endoscopic assessment of the surgical site.     

An update on the novel approaches towards skills assessment of ophthalmology residents in the Indian scenario

An essential part of the teaching-learning paradigm is assessment. It is one of the ways to achieve feedback for the various methods that have been used to impart a particular skill. This is true of ophthalmology training, where various clinical and surgical skills are learned as part of the residency program. In preparation for residents to become proficient ophthalmologists, both formative and summative assessments are of paramount importance. At present, assessment is primarily summative in the form of a university examination, including theory and practical examinations that are conducted at the end of the three years of residency. A formative assessment can make course corrections early on, allowing for an improved understanding of the subject and the acquisition of clinical and surgical skills. Formative assessments also allow us to customize the teaching methodology considering individual residents’ learning capabilities. In addition, formative assessments have the advantage of alleviating the stress of a “final” examination, which could sometimes result in a less-than-optimum performance by the residents. The COVID-19 pandemic has forced us to adopt new teaching methods, which has led to the adoption of changes in assessment. In this regard, we discuss the different assessment tools available, their pros and cons, and how best these tools can be made applicable in the setting of an ophthalmology residency program.