Descemet's stripping without endothelial keratoplasty.

PURPOSE OF REVIEW: To summarize the recent literature regarding descemetorhexis stripping without endothelial keratoplasty (DWEK), increasingly referred to as Descemet's stripping only (DSO). To report the characteristic clinical, confocal and histologic findings associated with this procedure. RECENT FINDINGS: Reported clearance rates following DSO range from 63 to 100% in recent series, with variation between surgical techniques. Topical Rho-kinase inhibitor has been reported as successfully salvaging failing cases. Its use as an adjuvant to the surgery is gaining widespread adoption with the results of early series now arriving. Apart from a phenotype of central guttata with clear periphery, patient characteristics which determine success remain elusive. Surgical factors affecting success are increasingly well understood, with stromal injury felt to be a retardant to healing. Characteristic clinical signs have been observed and are described herein. Clinical, confocal and light microscopic images are obtained from patients in clinical trials of DSO with ripasudil. SUMMARY: DSO is gaining acceptance as a surgical option for a subset of patients with Fuchs' Dystrophy. The addition of Rho-associated kinase inhibitor appears to improve predictability but further results to this effect must be published and scrutinized.

Noninferiority of miltefosine versus meglumine antimoniate for cutaneous leishmaniasis in children.

BACKGROUND: Children have a lower response rate to antimonial drugs and higher elimination rate of antimony (Sb) than adults. Oral miltefosine has not been evaluated for pediatric cutaneous leishmaniasis. METHODS: A randomized, noninferiority clinical trial with masked evaluation was conducted at 3 locations in Colombia where Leishmania panamensis and Leishmania guyanensis predominated. One hundred sixteen children aged 2-12 years with parasitologically confirmed cutaneous leishmaniasis were randomized to directly observed treatment with meglumine antimoniate (20 mg Sb/kg/d for 20 days; intramuscular) (n = 58) or miltefosine (1.8-2.5 mg/kg/d for 28 days; by mouth) (n = 58). Primary outcome was treatment failure at or before week 26 after initiation of treatment. Miltefosine was noninferior if the proportion of treatment failures was ≤15% higher than achieved with meglumine antimoniate (1-sided test, α = .05). RESULTS: Ninety-five percent of children (111/116) completed follow-up evaluation. By intention-to-treat analysis, failure rate was 17.2% (98% confidence interval [CI], 5.7%-28.7%) for miltefosine and 31% (98% CI, 16.9%-45.2%) for meglumine antimoniate. The difference between treatment groups was 13.8%, (98% CI, -4.5% to 32%) (P = .04). Adverse events were mild for both treatments. CONCLUSIONS: Miltefosine is noninferior to meglumine antimoniate for treatment of pediatric cutaneous leishmaniasis caused by Leishmania (Viannia) species. Advantages of oral administration and low toxicity favor use of miltefosine in children. CLINICAL TRIAL REGISTRATION: NCT00487253.

Late onset of microbial keratitis after laser in situ keratomileusis surgery: case series.

PURPOSE: To report predisposing factors, clinical features, microbiology spectrum, antibiotic resistance, antimicrobial therapy, and outcomes of patients with a previous laser in situ keratomileusis (LASIK) surgery and diagnosed with presumed microbial keratitis. SETTING: Sydney Eye Hospital, Sydney, New South Wales, Australia. DESIGN: Retrospective case review. METHODS: Patients were identified from pathology and hospital coding data from 2012 to 2016. Inclusion criteria were all patients with a previous LASIK surgery, a presumed diagnosis of microbial keratitis, and a corneal scrape performed and aged older than 18 years. Demographics, clinical details, and outcomes were collated from the medical records. RESULTS: Sixteen patients were included, with median age of 41.5 years (range 22 to 85 years) and 56.2% of women. The median time between LASIK procedure and microbial keratitis presentation was 38.3 months (interquartile range 6.7 to 77.45 months). Cultures were positive for bacteria in 12 (75%) of 16 scrapes. Of the bacterial isolates, 12 (85.7%) were gram-positive and 2 (14.3%) gram-negative. Sensitivity profiles for the isolated bacteria were similar between fortified antibiotics (cefalotin and gentamicin) and commercial products (chloramphenicol and ofloxacin). Complications included the need for tectonic grafts, nonhealing epithelial defects, thinning, and neovascularization. CONCLUSIONS: Late onset of keratitis after LASIK can occur with no positive cultures for nontuberculous mycobacteria, no interface involvement, and no other usual features reported in case series of infectious keratitis in LASIK patients. It has a similar clinical course to non-LASIK keratitis, such that the surgery may not have been a risk factor for infection.

Diagnostic Sensitivity of Different Reference Bodies When Using Scheimpflug Tomography in a Myopic Population with Keratoconus.

PURPOSE: To establish which reference body offers the greatest sensitivity in keratoconus (KC) diagnosis, obtain normative data for the myopic population with toric ellipsoid reference bodies, and determine the cutoff points for a population with KC. METHODS: A retrospective, observational study of the entire Scheimpflug tomographer database of the Fundación Jiménez Díaz in Madrid was conducted to identify a normal myopic and a KC myopic population. Three different reference bodies were tested on all patients: best fit sphere (BFS), best fit toric ellipsoid with fixed eccentricity (BFTEFE), and best fit toric ellipsoid (BFTE). Anterior and posterior elevation measurements at the apex and thinnest point were recorded, as well as the root mean square of posterior elevations (RMS-P). Normative data were extracted, and receiver operating characteristic (ROC) curves were generated to obtain cutoff points between the normal and KC population. RESULTS: A total of 301 eyes were included, comprising 219 normal myopic and 82 myopic KC eyes. BFS and BFTEFE produced the best results when measuring posterior elevation at the thinnest point. BFTE had better sensitivity with the RMS-P. From all measurements, best sensitivity (100%) was achieved with a cutoff point of 8 µm of posterior elevation at the thinnest point using the BFTEFE. BFTE was found to hide the cone in certain patients. CONCLUSIONS: Posterior elevation measured at the thinnest point with a BFTEFE is the best-performing parameter and, therefore, is recommended to discriminate between normal and KC patients within a myopic population.

Possible links between sickle cell crisis and pentavalent antimony.

For over 60 years, pentavalent antimony (Sb(v)) has been the first-line treatment of leishmaniasis. Sickle cell anemia is a disease caused by a defect in red blood cells, which among other things can cause vasooclusive crisis. We report the case of a 6-year-old child with leishmaniasis who during treatment with meglumine antimoniate developed a sickle cell crisis (SCC). No previous reports describing the relationship between antimonial drugs and sickle cell disease were found. Reviews of both the pathophysiology of SCC and the mechanism of action of Sb(v) revealed that a common pathway (glutathione) may have resulted in the SCC. ChemoText, a novel database created to predict chemical-protein-disease interactions, was used to perform a more expansive and systematic review that was able to support the association between glutathione, Sb(v), and SCC. Although suggestive evidence to support the hypothesis, additional research at the bench would be needed to prove Sb(v) caused the SCC.

Regulatory T cells in the pathogenesis and healing of chronic human dermal leishmaniasis caused by Leishmania (Viannia) species.

BACKGROUND: The inflammatory response is prominent in the pathogenesis of dermal leishmaniasis. We hypothesized that regulatory T cells (Tregs) may be diminished in chronic dermal leishmaniasis (CDL) and contribute to healing during treatment. METHODOLOGY/PRINCIPAL FINDINGS: The frequency and functional capacity of Tregs were evaluated at diagnosis and following treatment of CDL patients having lesions of ≥6 months duration and asymptomatically infected residents of endemic foci. The frequency of CD4(+)CD25(hi) cells expressing Foxp3 or GITR or lacking expression of CD127 in peripheral blood was determined by flow cytometry. The capacity of CD4(+)CD25(+) cells to inhibit Leishmania-specific responses was determined by co-culture with effector CD4(+)CD25(-) cells. The expression of FOXP3, IFNG, IL10 and IDO was determined in lesion and leishmanin skin test site biopsies by qRT-PCR. Although CDL patients presented higher frequency of CD4(+)CD25(hi)Foxp3(+) cells in peripheral blood and higher expression of FOXP3 at leishmanin skin test sites, their CD4(+)CD25(+) cells were significantly less capable of suppressing antigen specific-IFN-γ secretion by effector cells compared with asymptomatically infected individuals. At the end of treatment, both the frequency of CD4(+)CD25(hi)CD127(-) cells and their capacity to inhibit proliferation and IFN-γ secretion increased and coincided with healing of cutaneous lesions. IDO was downregulated during healing of lesions and its expression was positively correlated with IFNG but not FOXP3. CONCLUSIONS/SIGNIFICANCE: The disparity between CD25(hi)Foxp3(+) CD4 T cell frequency in peripheral blood, Foxp3 expression at the site of cutaneous responses to leishmanin, and suppressive capacity provides evidence of impaired Treg function in the pathogenesis of CDL. Moreover, the concurrence of increased Leishmania-specific suppressive capacity with induction of a CD25(hi)CD127(-) subset of CD4 T cells during healing supports the participation of Tregs in the resolution of chronic dermal lesions. Treg subsets may therefore be relevant in designing immunotherapeutic strategies for recalcitrant dermal leishmaniasis caused by Leishmania (Viannia) species.