Discontinuation of tyrosine kinase inhibitor in chronic myeloid leukemia: a retrospective cohort in east occitania.

Tyrosine kinase inhibitor (TKI) discontinuation in chronic phase chronic myeloid leukemia (CML) patients has been examined in a real-life setting in the east occitania region of France. We have collected sex, age, prognostic scores, pre-TKI treatment, TKI length and response, relapse data from patients who had stopped TKI in prolonged complete molecular remission (CMR), and analyzed relapse risk factors. Sixty consecutive patients were included from january 2010 to december 2016. Sixteen received pre-TKI treatment. Fifty-three received a first-generation TKI, and seven had a second-generation TKI in first-line therapy. The median TKI time to achieve CMR was 20.5 months [5-137]. The median TKI length before discontinuation treatment was 73 months [12-158]. Twenty-two patients (37%) relapsed with a median time to relapse of 6 months [3-27]. An intermediate or high Sokal score was the only relapse risk factor (HR = 3.32, p < 0.05) associated with relapse after TKI discontinuation. TKI discontinuation was possible without relapse for half of the patients in chronic phase CML. In a real-life cohort, a high-risk Sokal score at diagnosis appears to be an adverse prognosis feature for TKI discontinuation.

Evaluation of diclofenac sodium 0.1% ophthalmic solution in the treatment of ocular symptoms after bilateral radial keratotomy.

PURPOSE: Patients frequently have ocular pain, photophobia, foreign-body sensation, and burning/stinging after radial keratotomy. This study was a prospective, randomized, double-masked, multicenter, fellow-eye comparison of diclofenac sodium (Voltaren Ophthalmic, 0.1% solution) and placebo for controlling these ocular symptoms after bilateral radial keratotomy. METHODS: Patients who were pain free in both eyes before surgery were randomly assigned to treatment with diclofenac sodium in one eye and placebo in the other. One drop of each masked trial medication was administered 30-60 min before surgery, 5 min and 6 h after surgery, at bedtime on the day of surgery, and four times daily for 2 additional days. Patients evaluated ocular symptoms in each eye 0.5, 1, 2, 4, 6, 24, and 48 h after surgery and provided a global evaluation 6, 24, and 48 h after surgery. For each assessment, the difference in scores between eyes was analyzed by using a paired t test. RESULTS: Diclofenac sodium was significantly (p < 0.001) superior to placebo in controlling each ocular symptom at each interval after surgery and for patient global assessments 6, 24, and 48 h after surgery. CONCLUSION: Diclofenac sodium 0.1% ophthalmic solution is clinically effective in controlling adverse ocular symptoms occurring after bilateral radial keratotomy.

Analysis of corneal topography after automated lamellar keratoplasty.

PURPOSE: The purpose of the study is to evaluate the effects of myopic automated lamellar keratoplasty (ALK) on corneal topography. METHODS: The authors performed a retrospective study of computer-assisted topographic maps obtained before surgery and at the last follow-up visit of 9 patients (13 eyes) who underwent ALK without enhancement to correct moderate-to-high myopia during a 12-month period. RESULTS: Follow-up ranged from 3.5 to 13 months (mean, 5.8; standard deviation, 3.1). The mean manifest spherical equivalent changed from -10.5 +/- 2.2 diopters (D) before surgery to -1.1 +/- 1.8 D at the last follow-up visit. Mean simulated keratometry (Sim K) decreased from 45.6 +/- 1.9 D to 38.9 +/- 2.7 D. Mean corneal astigmatism increased from 1.3 +/- 0.8 D to 2.1 +/- 0.9 D. The mean surgically induced cylinder vector (calculated by vector analysis) was 1.1 +/- 0.6 D. Mean surface regularity index (SRI) and surface asymmetry index (SAI) increased from 0.37 +/- 0.38 and 0.32 +/- 0.43 before surgery to 1.00 +/- 0.32 (P < 0.001) and 0.75 +/- 0.36 (P = 0.01), respectively, at the last visit. A positive correlation was observed between the decrease in mean Sim K and the increase in manifest spherical equivalent (reduction of myopia) (r = 0.77, P = 0.002), increase in SRI (r = 0.73, P = 0.005), and increase in SAI (r = 0.58, P = 0.04). The change in manifest spherical equivalent was significantly less than the change in Slm K (P < 0.001). CONCLUSIONS: Myopic ALK significantly flattens the cornea and reduces myopia. However, it induces corneal astigmatism and decreases corneal surface regularity and symmetry. The degree of myopic correction, as well as the surgically induced corneal surface irregularity and asymmetry, is positively correlated with the amount of corneal flattering derived from the surgical procedure.

The spectrum of topography found in keratoconus.

In order to more completely understand the topographic changes associated with keratoconus we performed computer-analyzed, digitized, videokeratoscopy (CADVK) on 23 patients with clinically documented keratoconus, using the EH-270 Corneal Topographer (Visioptic, Houston, TX). The majority of analyzed eyes demonstrated the classic picture of a well defined zone of inferior to inferotemporal steepening. However, several other topographic patterns were noted, including: nasal, superior, and central steepening, as well as extension of the inferior steepening superiorly. Additionally, significant flattening was found in some portions of the cornea away from the cone, particularly in the superonasal quadrant. In all cases, the precise location and degree of steepening could be easily defined. Interestingly, for both typical and atypical topographic patterns, marked symmetry between eyes in each patient was noted. The use of CADVK may allow for a more thorough appreciation of the diverse and complex topographic abnormalities associated with keratoconus, information which could aid in contact lens management and design.

Corneal trauma: I--Classification and management.

Ocular trauma is common and frequently impairs vision. Injuries to the cornea account for approximately two thirds of ocular trauma. Appropriate detection, diagnosis, triage, and treatment decisions are needed in cases of corneal trauma to achieve maximum benefit for the traumatized patient. In this article, the prominent features of corneal trauma are reviewed, and a practical method of classification is presented to assist in management decisions.

The effect of collagen shields on rabbit corneal reepithelialization after chemical debridement.

We evaluated the effect of precarved collagen lenses on the kinetics of epithelial wound healing in an experimental model of corneal erosions. After induction of anesthesia, central corneal erosions of 5-mm diameter were created in New Zealand white rabbits using n-heptanol. Animals were randomly assigned either to the treatment group or to one of three control groups. Each animal in the treatment group received a precarved collagen shield made from porcine sclera. Immediately after creation of the corneal epithelial defects, topical fluorescein sodium was applied, and the corneas were photographed. Similar follow-up examinations were conducted at 5, 24, 30, 48, 72, and 96 hr after defect creation. Epithelial defect areas were calculated by projecting the photographic slides onto a computerized digitizing pad. Reepithelialization kinetics were compared for the four treatment groups. When initial wound size was taken into account, no significant difference between mean reepithelialization rates was noted. These results indicate that collagen lenses do not adversely affect the speed of corneal reepithelialization, and may, because of their documented biodegradibility and drug delivery capability, be useful in the clinical management of corneal epithelial erosions.

Results of penetrating keratoplasty for the treatment of corneal perforations.

We retrospectively analyzed 46 consecutive cases of penetrating keratoplasty performed as part of the treatment of corneal perforations; the minimum follow-up time after keratoplasty was 7 months. Predisposing conditions leading to perforation were an infectious keratitis in 26 eyes (57%), trauma in 14 eyes (30%), and corneal melt associated with ocular surface disorder in 6 eyes (13%). The success of penetrating keratoplasty in the treatment of corneal perforation depended on the timing of surgery and the cause of the perforation. If the perforation was traumatic in origin, delaying surgery for at least 3 months significantly improved the chances for graft success. Eighty percent of the penetrating keratoplasties delayed 3 months following primary repair of corneal laceration remained clear, and 50% of these patients had a visual acuity of 20/60 or better. If penetrating keratoplasties were performed for an infectious corneal perforation, grafts had a better chance to remain clear if surgery could be delayed. All grafts performed for corneal perforation associated with melting and ocular surface abnormalities failed.

Radial keratotomy: procedures.

The presently employed procedure of radial keratotomy is essentially unchanged from that developed by Fyodorov and introduced into the United States by Bores in 1978. The surgical procedure essentially consists of six basic steps: 1) application of appropriate anesthesia; 2) marking the visual axis; 3) marking the optical zone; 4) measuring the corneal thickness; 5) setting the depth of the blade; and 6) marking the corneal incisions. This review will carefully consider the pros and cons of many potential variations associated with each of these steps.

The use of concanavalin A to competitively inhibit Pseudomonas aeruginosa adherence to rabbit corneal epithelium.

Microbial adherence to corneal epithelial cells is the initial step in the development of infectious keratitis. In an attempt to inhibit this process, we evaluated the effects of concanavalin A (Con A) upon the adherence of Pseudomonas aeruginosa to injured rabbit corneal epithelial cells. A sterile 21-gauge needle was used to create linear epithelial injuries. Identical samples from suspensions of a pure strain of P. aeruginosa were placed on two groups of injured corneas. Prior to bacterial application, one group of corneas received topical application of Con A, a lectin that is capable of binding to alpha-D-mannose or alpha-D-glucose. The animals were sacrificed 1 hour after application of the bacteria. Scanning electron microscopy of the excised corneas revealed that, compared to the corneas that had not been exposed to Con A, those exposed to the lectin had significant fewer adherent P. aeruginosa bacilli. Additionally, only rare bacteria were noted adhering to the uninjured superficial epithelial cells. These results suggest that, by competitively binding to the exposed mannose and/or glucose groups on the surfaces of these cells, Con A is capable of inhibiting the adherence of P. aeruginosa to injured epithelial cells.

Scanning electron microscopic evaluation of the effects of intracameral injection of cyanoacrylate in the rabbit.

We examined, using scanning electron microscopy, the effects of the injection of an isobutyl cyanoacrylate into the rabbit anterior chamber. Injection of the adhesive produced a rapidly polymerized mass that remained in the anterior chamber throughout the course of the study. Additionally, an active inflammatory response was noted in the anterior chamber, characterized by a progressively enlarging "cocoon" of fibrin and inflammatory cells surrounding the polymerized adhesive, as well as inflammatory cells in the trabecular meshwork. Following cyanoacrylate injection, the corneal endothelial cells were noted to be swollen for the first 14 days of the study.

Intravitreal biocompatibility of mussel adhesive protein. A preliminary study.

Mussel adhesive protein (MAP) is a new tissue adhesive derived from the sea mussel Mytilus edulis. Rabbit eyes were injected intravitreally with 1 mg of MAP or balanced salt solution in order to determine the intraocular effects of this new biologic tissue adhesive. Two concentrations of MAP were used: one was undiluted and the other was diluted to a concentration of 1:10. A marked cellular inflammatory response, compared with the control eyes, was seen clinically in the vitreous cavity of animals in which MAP was used undiluted. This response persisted for up to two weeks and was suggestive of inflammatory response to a foreign protein. When MAP was used at a dilution of 1:10, a mild transient cellular reaction was observed in the vitreous; this cleared after seven days. There was no increase in intraocular pressure, and none of the eyes developed cataract or optic nerve damage. Fluorescein angiography demonstrated no vascular leakage and electroretinography was normal in all of the eyes at two weeks. Histopathologic evaluation of the eyes at 7 and 14 days after injection revealed localized cellular inflammation in the vitreous and adjacent retina when MAP was used undiluted, but no reaction in the control eyes or in eyes injected with MAP at 1:10 dilution. This preliminary study suggests that MAP produces a marked intraocular inflammatory reaction when used at full concentration. By diluting the adhesive, a less severe inflammatory response was observed, which cleared with no complications.

Herpes simplex keratitis in patients with acquired immune deficiency syndrome.

Acquired immune deficiency syndrome (AIDS) is associated with a wide spectrum of systemic and ocular infectious diseases. Little information is known about herpes simplex virus type 1 (HSV-1) keratoconjunctivitis in association with AIDS. The authors present six cases of recurrent HSV keratitis occurring in AIDS patients. Features of the herpetic keratitis in these patients included unilateral dendritic or geographic epithelial keratopathy; predilection for peripheral versus central corneal involvement; one to three recurrences per patient over a mean observation period of 17 months, with a median dendrite-free interval of 7 months; and a moderately prolonged clinical course with a median healing time of 3 weeks using topical antiviral therapy. Only one of six cases had stromal infiltrative involvement. These cases raise the question of whether the immunologic abnormalities associated with AIDS may affect the clinical characteristics and course of HSV keratitis.

Preliminary evaluation of two experimental surgical adhesives in the rabbit cornea.

We examined the clinical and histopathologic effects of the instillation of two surgical adhesives in the corneal stroma of rabbits. The adhesives examined in this study included a butyl-2-cyanoacrylate (CA) and a combination of a mussel-derived polyphenolic protein (MAP) with an enzyme polymerizer (COX). In this study, either one of the adhesives or balanced saline solution (as a control) was instilled directly into the corneal stroma following the surgical creation of a perilimbal intralamellar pocket. Animals were examined on a regular basis for a 60-day period following instillation and, at predetermined time points, sacrificed for histopathologic evaluation. The group of animals that received intracorneal instillations of CA consistently manifested early and progressive stromal neovascularization of the affected corneas. Histopathologic examination confirmed the progressive neovascularization, as well as a noticeable inflammatory response surrounding the adhesive. In contrast, instillation of the MAP-COX adhesive produced neovascular and inflammatory responses that were later in onset and milder in degree than those observed with CA. In this experimental model, the MAP-COX adhesive appeared to be better tolerated than did the CA.

Fluorescein-conjugated lectin visualization of fungi and acanthamoebae in infectious keratitis.

The authors investigated the efficacy of two fluorescein-conjugated lectins (FCLs), concanavalin A (F-ConA) and wheat germ agglutinin (F-WGA), to visualize microorganisms from clinical specimens with documented mycotic and acanthamoebic keratitis. Corneal scrapings from 18 patients with culture-proven keratomycosis and deparaffinized histopathologic specimens from five culture-proven cases of acanthamoebic keratitis were evaluated. The F-ConA provided consistently bright staining of the mycotic structures in each of the corneal scrapings. Both F-ConA and F-WGA stained acanthamoebic trophozoites and cysts in the histopathologic specimens. In both the corneal scrapings and the histopathologic specimens, the microorganisms were easily differentiated from background corneal cells and tissue. These staining patterns correlate well with the results from experimental studies, and with the known cell wall carbohydrate compositions for fungi and acanthamoebae. This study provides further evidence that FCLs (particularly F-ConA) may eventually become effective first-line stains for the visualization of microorganisms in specimens from ocular infections.

The use of fluorescein-conjugated lectins for visualizing atypical mycobacteria.

We investigated the feasibility of using fluorescein-conjugated lectins for visualizing and differentiating two species of atypical mycobacteria. Pure cultures of Mycobacterium fortuitum and Mycobacterium chelonei were established, as was an experimental model of infectious keratitis involving these two organisms. Samples from the pure cultures and corneal scrapings were placed on glass slides, fixed, and incubated with one of a panel of 22 fluorescein-conjugated lectins. The slides were examined using an epifluorescence microscope. Fluorescein-conjugated concanavalin A brightly stained both species of atypical mycobacteria, in both the pure culture and experimental keratitis samples. Several additional fluorescein-conjugated lectins (wheat germ agglutinin, succinylated wheat germ agglutinin, Phaseolus vulgaris erythroagglutinin, and Psophocarpus tetragonolobus agglutinin) brightly stained M chelonei, but only moderately stained M fortuitum. These staining patterns are consistent with the known carbohydrate compositions of the cell walls of atypical mycobacteria and suggest that fluorescein-conjugated lectins may be useful for the visualization of these organisms in corneal infections.

Lack of toxicity of a topical recombinant interferon alpha.

We evaluated the potential ocular surface toxicity of a recombinant interferon-alpha (IFN alpha) preparation on rabbit eyes. Topical application of this interferon (1 x 10(6) U/day in each eye) for 6 weeks produced no discernible conjunctival or corneal abnormalities on clinical, histopathologic, or ultrastructural evaluations. We believe that this recombinant IFN alpha preparation is not toxic to the ocular surface of rabbits.