PD-L1 expression in the tumor immune microenvironment is recognized as both a prognostic and predictive biomarker in patients with cutaneous melanoma, a finding closely related to its adaptive (IFN-γ-mediated) mechanism of expression. Approximately 35% of cutaneous melanomas express PD-L1, however, the expression patterns, levels, and prevalence in rarer melanoma subtypes are not well described. We performed immunohistochemistry for PD-L1 and CD8 on 200 formalin-fixed paraffin-embedded specimens from patients with acral (n = 16), mucosal (n = 36), uveal (n = 103), and chronic sun-damaged (CSD) (n = 45) melanomas (24 lentigo maligna, 13 ‘mixed’ desmoplastic, and 8 ‘pure’ desmoplastic melanomas). CD8+ tumor-infiltrating lymphocyte (TIL) densities were characterized as mild, moderate, or severe, and their geographic association with PD-L1 expression was evaluated. Discrete lymphoid aggregates, the presence of a spindle cell morphology, and the relationship of these features with PD-L1 expression were assessed. PD-L1 expression was observed in 31% of acral melanomas, 44% of mucosal melanomas, 10% of uveal melanomas, and 62% of CSD melanomas (P<0.0001). Compared to our previously characterized cohort of cutaneous melanomas, the proportion of PD-L1(+) tumors was lower in uveal (P = 0.0002) and higher in CSD (P = 0.0073) melanomas, while PD-L1 expression in the acral and mucosal subtypes was on par. PD-L1 expression in all subtypes correlated with a moderate–severe grade of CD8+ TIL (all, P<0.003), supporting an adaptive mechanism of expression induced during the host antitumor response. The tumor microenvironments observed in CSD melanomas segregated by whether they were the pure desmoplastic subtype, which showed lower levels of PD-L1 expression when compared to other CSD melanomas (P = 0.047). The presence of lymphoid aggregates was not associated with the level of PD-L1 expression, while PD-L1(+) cases with spindle cell morphology demonstrated higher levels of PD-L1 than those with a nested phenotype (P<0.0001). Our findings may underpin the reported clinical response rates for anti-PD-1 monotherapy, which vary by subtype.

Background A pterygium is a fleshy, wing-shaped growth from the conjunctiva, crossing over the limbus onto the cornea. Prevalence ranges widely around the world. Evidence suggests that ultraviolet light is a major contributor in the formation of pterygia. Pterygia impair vision, limit eye movements, and can cause eye irritation, foreign body sensation, and dryness. In some susceptible patients, the pterygium can grow over the entire corneal surface, blocking the visual axis. Surgery is the only effective treatment for pterygium, though recurrences are common. With simple excision techniques (that is, excising the pterygium and leaving bare sclera), the risk of recurrence has been reported to be upwards of 80%. Pterygium excision combined with a tissue graft has a lower risk of recurrence. In conjunctival autograft surgery, conjunctival tissue from another part of the person’s eye along with limbal tissue is resected in one piece and used to cover the area from which the pterygium was excised. Another type of tissue graft surgery for pterygium is amniotic membrane graft, whereby a piece of donor amniotic membrane is fixed to the remaining limbus and bare sclera area after the pterygium has been excised. Objectives The objective of this review was to assess the safety and effectiveness of conjunctival autograft (with or without adjunctive therapy) compared with amniotic membrane graft (with or without adjunctive therapy) for pterygium. We also planned to determine whether use of MMC yielded better surgical results and to assess the direct and indirect comparative costs of these procedures. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (Issue 10, 2015), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to November 2015), EMBASE (January 1980 to November 2015), PubMed (1948 to November 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (1982 to November 2015), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) (last searched 21 November 2014), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 23 November 2015. Selection criteria We included in this review randomized controlled trials that had compared conjunctival autograft surgery (with or without adjunctive therapy) with amniotic membrane graft surgery (with or without adjunctive therapy) in people with primary or recurrent pterygium. Data collection and analysis Two review authors independently screened search results and assessed full-text reports from among the potentially eligible trials. Two review authors independently extracted data from the included trials and assessed the trial characteristics and risk of bias. The primary outco...

Angle kappa is the difference between the pupillary and visual axis. This measurement is of paramount consideration in refractive surgery, as proper centration is required for optimal results. Angle kappa may contribute to MFIOL decentration and its resultant photic phenomena. Adjusting placement of MFIOLs for angle kappa is not supported by the literature but is likely to help reduce glare and haloes. Centering LASIK in angle kappa patients over the corneal light reflex is safe, efficacious, and recommended. Centering in-between the corneal reflex and the entrance pupil is also safe and efficacious. The literature regarding PRK in patients with an angle kappa is sparse but centering on the corneal reflex is assumed to be similar to centering LASIK on the corneal reflex. Thus, centration of MFIOLs, LASIK, and PRK should be focused on the corneal reflex for patients with a large angle kappa. More research is needed to guide surgeons’ approach to angle kappa.

Numerous brands and types of artificial tears are available on the market for the treatment of dysfunctional tear syndrome. Past literature has focused on comparing the components of these products on patient’s clinical improvement. The wide array of products on the market presents challenges to both clinicians and patients when trying to choose between available tear replacement therapies. Different formulations affect patients based on etiology and severity of disease. In order to provide an unbiased comparison between available tear replacement therapies, we conducted a literature review of existing studies and National Institutes of Health clinical trials on commercially available, brand name artificial tears. Outcomes evaluated in each study, as well as the percent of patients showing clinical and symptomatic improvement, were analyzed. Fifty-one studies evaluating different brands of artificial tears, and their efficacy were identified. Out of the 51 studies, 18 were comparison studies testing brand name artificial tears directly against each other. Nearly all formulations of artificial tears provided significant benefit to patients with dysfunctional tear syndrome, but some proved superior to others. From the study data, a recommended treatment flowchart was derived.

PurposeTo report the rate of postoperative ectasia after laser-assisted in situ keratomileusis (LASIK) with femtosecond laser-assisted flap creation, in a population of patients with no identified preoperative risk factors.MethodsA retrospective case review of 1,992 eyes (1,364 patients) treated between March 2007 and January 2009 was conducted, with a follow up of over 4 years. After identifying cases of ectasia, all the patient charts were examined retrospectively for preoperative findings suggestive of forme fruste keratoconus (FFKC).ResultsFive eyes of four patients with post-LASIK ectasia were identified. All eyes passed preoperative screening and received bilateral LASIK. One of the five patients developed ectasia in both eyes. Three patients retrospectively revealed preoperative topography suggestive of FFKC, while one patient had no identifiable preoperative risk factors. Upon review of all the charts, a total 69 eyes, including four of the five eyes with ectasia, were retrospectively found to have topographies suggestive of FFKC.ConclusionWe identified four cases of post-LASIK ectasia that had risk factors for FFKC on reexamination of the chart and one case of post-LASIK ectasia with no identifiable preoperative risk factors. The most conservative screening recommendations would not have precluded this patient from LASIK. The rate of purely iatrogenic post-LASIK ectasia at our center was 0.05% (1/1,992), and the total rate of post-LASIK ectasia for our entire study was 0.25% (1/398). The rate of eyes with unrecognized preoperative FFKC that developed post-LASIK ectasia was 5.8% (1/17).

Metagenomic characterization of complex biomes remains challenging. Here we describe a modification of digital karyotyping—biome representational in silico karyotyping (BRISK)—as a general technique for analyzing a defined representation of all DNA present in a sample. BRISK utilizes a Type IIB DNA restriction enzyme to create a defined representation of 27-mer DNAs in a sample. Massively parallel sequencing of this representation allows for construction of high-resolution karyotypes and identification of multiple species within a biome. Application to normal human tissue demonstrated linear recovery of tags by chromosome. We apply this technique to the biome of the oral mucosa and find that greater than 25% of recovered DNA is nonhuman. DNA from 41 microbial species could be identified from oral mucosa of two subjects. Of recovered nonhuman sequences, fewer than 30% are currently annotated. We characterized seven prevalent unknown sequences by chromosome walking and find these represent novel microbial sequences including two likely derived from novel phage genomes. Application of BRISK to archival tissue from a nasopharyngeal carcinoma resulted in identification of Epstein-Barr virus infection. These results suggest that BRISK is a powerful technique for the analysis of complex microbiomes and potentially for pathogen discovery.

No author has a financial or proprietary interest in any material or method mentioned.

PurposeTo evaluate the incidence rate and indications for explantation of Verisyse phakic intraocular lenses (pIOLs) over a 13.6 year period.Subjects and methodsCase series describing six cases of explantation of Verisyse pIOLs, out of 213 eyes with Verisyse pIOLs, implanted over a 13.6 year period by one surgeon at one institution, with mean follow-up of 5.6 years per eye.ResultsFour pIOLs were removed to facilitate extraction of a visually significant cataract, one was removed due to both cataract formation and development of corneal decompensation, and another was removed due to development of localized peripheral corneal decompensation. The incidence rate of pIOL removal was five per 1,000 patient-years with pIOL. Mean time from insertion of pIOL to cataract removal was 9.3 years (range 4.0–12.6 years). Mean time from insertion of pIOL to development of corneal decompensation was 10 years (range 6.9–13 years). There was no increase in the rate of cataract extraction in the pIOL population compared to the general population.ConclusionCataracts may develop in patients with pIOLs, necessitating removal of the pIOL. Corneal decompensation is a serious complication that appears to be directly related to pIOLs. Corneal decompensation can occur up to 13 years following implantation of pIOLs, and long-term follow-up is important to monitor for this complication.