Physicochemical and microbiological stability of insulin eye drops in an artificial tear vehicle used in the treatment of refractory neurotrophic keratopathy.

Neurotrophic keratopathy (NK) is a degenerative corneal disease with a loss of corneal sensitivity and impairment of corneal healing. Low dose insulin eyedrops have been shown to be a simple and effective treatment for refractory NK when the response to the usual treatment is incomplete. At present, there are no commercially available forms, and there is no data regarding the stability of these products as prepared by compounding pharmacies. In this work, we studied the physicochemical and microbiological stability of an insulin ophthalmic formulation obtained by mixing insulin lispro in artificial tears with a polyethylene and propylene glycol base. The stability of this 1IU/mL insulin ophthalmic formulation was analysed for 12 months in low-density polyethylene (LDPE) multidose eye droppers at 4°C. The studied parameters of physicochemical stability were: visual inspection, turbidity, UV spectral absorption, osmolality and pH. In addition, insulin and m-cresol concentrations and quantification of impurities (insulin covalent aggregates and insulin fragments) were studied thanks to the development of a new Size Exclusion Chromatographic method. For unopened eye droppers, all tested physicochemical parameters remained stable for 12 months at 4°C, and excellent microbiological stability was obtained. In conditions of simulated use, these parameters also remained stable for one month at 4°C, and no impact of potential temperature rises on the insulin and m-cresol concentrations in the insulin eyedropper was observed.

[Corneal perforation with tyrosine kinase inhibitor chemotherapy: REGORAFENIB]. / Perforation cornéenne sous chimiothérapie inhibiteur des tyrosines kinases : REGORAFENIB.

INTRODUCTION: Tyrosine kinase inhibitors (TKIs) are active in a variety of metastatic cancers. They have a good general tolerance with mainly hepatic and dermatological side effects. Rarely, ophthalmologic side effects may occur: eyelash abnormalities, eyelids abnormalities, disorders of the ocular surface with ocular dryness or even corneal erosions that can even lead to perforation. Regorafenib is a new oral multi-targeted tyrosine kinase inhibitor that inhibits multiple protein kinases, including those involved in tumor angiogenesis, oncogenesis and tumor microenvironment. CASE DESCRIPTION: We describe, to the best of our knowledge, the first case of complicated bilateral ulcers of corneal perforation in a patient under REGORAFENIB. OBSERVATION: 20-year-old patient with metastatic chondrosarcomas of the pelvis, mandible and thorax received chemotherapy with REGORAFENIB. A few weeks after initiation of treatment, he experienced an increased dry eye syndrome associated with bilateral corneal ulcers complicated by perforation. Despite discontinuation of chemotherapy and maximal medical and surgical treatment (iterative amniotic membrane grafts and corneal transplantation), the progression was unfavorable. DISCUSSION: This is the first known case of corneal perforation under REGORAFENIB. The pathophysiology is multifactorial. On the one hand, this chemotherapy targets angiogenesis (VEGFR), oncogenesis (KIT, RET, RAF1, BRAF) and the tumor microenvironment (PDGFR, FGFR). On the other hand, other triggers are added, namely mixed dry eye syndrome, hypovitaminosis A (anorexia), the neurotrophic component, as well as the toxicity of chemotherapy via tears. CONCLUSION: First described case of corneal perforation under REGORAFENIB, non-regressive at the end of chemotherapy, and despite medical and surgical treatments. Ophthalmologic surveillance is therefore necessary for patients under chemotherapy with tyrosine kinase inhibitors, as serious ocular complications, especially corneal ones, may occur.

[Interstitial keratitis diagnosis and treatment (French translation of the article)]. / Kératites interstitielles : prise en charge diagnostique et thérapeutiques.

Interstitial keratitis is a non-ulcerative, non-suppurative, more or less vascularized inflammation of the corneal stroma. The corneal lesions result from the host response to bacterial, viral (40% of cases) or parasitic antigens, or from an autoimmune response (1% of cases) without active corneal infection. The natural history of the disease is divided into two phases : acute and cicatricial. This type of keratitis is less common than ulcerative bacterial keratitis, but it is a non-negligible cause of visual loss. It is associated with systemic or infectious disease and requires early diagnosis and appropriate treatment to optimize visual prognosis and avoid other complications.

Interstitial keratitis diagnosis and treatment.

Interstitial keratitis is a non-ulcerative, non-suppurative, more or less vascularized inflammation of the corneal stroma. The corneal lesions result from the host response to bacterial, viral (40% of cases) or parasitic antigens, or from an autoimmune response (1% of cases) without active corneal infection. The natural history of the disease is divided into two phases: acute and cicatricial. This type of keratitis is less common than ulcerative bacterial keratitis, but it is a non-negligible cause of visual loss. It is associated with systemic or infectious disease and requires early diagnosis and appropriate treatment to optimize visual prognosis and avoid other complications.

[Visual outcomes after Descemet's membrane endothelial keratoplasty]. / Étude de la réhabilitation visuelle après kératoplastie endothéliale manuelle.

OBJECTIVES: Evaluation and monitoring at 6 months after Descemet's membrane endothelial keratoplasty (DMEK) in patients with Fuchs endothelial dystrophy and study of factors influencing visual rehabilitation and postoperative quality of life. METHODS: Prospective, consecutive, interventional study of 35 eyes of 32 patients with Fuchs endothelial dystrophy who underwent surgery from February 2015 to February 2016 by DMEK. Measurement at D10, M1, M3, M6 of visual acuity, graft endothelial cell density, pachymetry, and intraocular pressure, and performance at M6 of aberrometry, macular OCT and a quality of life survey (NEI-VFQ-25). Post-DMEK aberrations are compared to those from control patients selected for refractive surgery. RESULTS: Visual acuity improvement at 6 months was statistically significant (P<0.0001), as well as pachymetry decrease (P<0.0001), endothelial cell loss (P<0.0001) and intraocular pressure increase (P=0.003). We observed a statistically significant difference between post-DMEK aberrations and those of control subjects for all aberrations from 2nd to 5th order. There were no postoperative correlations between visual acuity, pachymetry, intraocular pressure, or endothelial cell loss. The global quality of life score at six months was 87, corresponding to a good quality of life. We did not find a link between the global NEI-VFQ-25 score and visual acuity or visual aberrations. Ninety percent of patients surveyed reported a postoperative general improvement in quality of life at M6. CONCLUSION: DMEK provides good visual rehabilitation and an improvement in quality of life for patients with Fuchs endothelial dystrophy. Higher order optical aberrations in these patients, although higher than in a healthy population, are negligible and have no impact on quality of vision or postoperative quality of life.

[Ocular syphilis: 9 cases]. / Syphilis oculaire : à propos de 9 cas.

Syphilis is a disease with ocular involvement may be opening and cover all ocular structures. The objective of the study was to retrospectively identify and describe all cases of ocular syphilis diagnosed in the ophthalmology department of Besançon University Hospital from March 2004 to April 2014. Between March 2004 and April 2014, we diagnosed and monitored 9 male patients (13 eyes) with ocular syphilis (1 interstitial keratitis, chorioretinitis associated with a 1 hyalite, 3 panuvéites, 1 chorioretinitis after placoid, 3 bilateral papillary edema). Patients had a mean age of 52.6 years (32-77 years) at diagnosis and the inaugural symptoms were in 100% of cases decreased visual acuity. The follow-up period ranged from 1 month to 5 years. The curative treatment included intravenous antibiotics penicillin G for 3 weeks. All patients had an improvement in their AV (AV initial range "counting fingers" and 0.6 versus AV final between 0.5 and 1 in decimal scale). Syphilis is a disease currently on the rise. It must be systematically sought before any inflammatory disease of the eye or papilledema.

[Femtosecond-assisted Ferrara intrastromal corneal ring implantation for treatment of keratoconus: Functional outcomes at one year]. / Anneaux intra-cornéens Ferrara implantés au laser femtoseconde dans le traitement du kératocône : résultats fonctionnels à 1 an.

INTRODUCTION: Intrastromal corneal rings (ICR) have been used for several years for the correction of irregular astigmatism in patients with keratoconus. OBJECTIVE: To evaluate the effectiveness of femtosecond-assisted ICR implantation for treatment of keratoconus and to define predictive factors of success. PATIENTS AND METHODS: We undertook a retrospective study of patients with keratoconus who underwent femtosecond-assisted Ferrara ICR implantation between December 2012 and May 2014 at the University Hospital of Besançon. To determinate predictive factors of success, we divided patients into 2 groups based on the gain of at least two lines of best corrected visual acuity (BCVA) at 1 year after surgery ("good responders") or the gain of only one line of BCVA, no change, or the loss of lines of BCVA ("poor responders"). For each group, we analyzed preoperative refractive and keratometric values. Moreover, to verify if preoperative visual acuity could be a predictive factor of success, four groups were created based on initial visual acuity, and postoperative BCVA was compared. RESULTS: We retrospectively studied 32 eyes of 29 patients with keratoconus who underwent femtosecond-assisted Ferrara ICR implantation between December 2012 and May 2014 at the University Hospital of Besançon. From one month to 1 year postoperatively, we observed a significant improvement in BCVA and a significant decrease in cylinder and keratometry values (P<0.05). In total, 90.6% of patients had an increase in visual acuity (VA) of at least one line within 1 year while 9.4% had a decrease or stability of their VA. The average cylinder value decreased from -4.81±2.45 diopters (D) preoperatively to -2.39±1.94 D (P<0.001) at 1 year postoperatively, and the average of the maximum keratometry from 51.14±3.89 D to 48.52±4.00 D (P<0.05). Four predictive factors of success were statistically significant: type of ectasia (type 1 or 2), stage of keratoconus (Krumeich 1 or 2), implantation of only 1 ICR and a preoperative VA less than 0.4 (decimal scale). Eighty-six percent of patients with an initial VA<0.4 (decimal scale) gained 2 lines of BCVA within 1 year and 80% 3 lines versus 52% and 41%, respectively for patients with initial VA≥0.4 (decimal scale). CONCLUSION: Femtosecond-assisted Ferrara ICR implantation for treatment of keratoconus is a reliable and reversible technique. Implantation results in greater efficiency for patients with moderately advanced asymmetric keratoconus with an initial VA<0.4 (decimal scale).

[Quality of life in patients wearing scleral lenses]. / Qualité de vie des patients équipés en verres scléraux.

OBJECTIVE: To evaluate the contribution of scleral lenses in terms of improving the quality of life in the treatment of astigmatism after penetrating keratoplasty or in keratoconus. METHODS: We conducted an observational retrospective study, evaluating quality of life (QOL) of patients who failed to adapt to RPG lenses, fitted with SPOT(®) scleral lenses between October 2007 and March 2011 in the University Hospital of Besançon Department of Ophthalmology. QOL was assessed before and after scleral lens adaptation with the French version of the National Eye Institute Visual Function Questionnaire 25 (NEI-VFQ 25). RESULTS: We included 47 patients (83 eyes) fitted with scleral lenses on one or both eyes: 56 eyes with keratoconus and 27 post-keratoplasty eyes. The average duration of wearing scleral lenses was 18±10months and the average wearing time was 14±3hours per day. The rate of participation in the survey was 86.5% (41 patients). Visual acuity in the better eye progressed from 0.68±0.46 to 0.15±0.17 logMAR at the 6th month after scleral lens adaptation (P<0.0001). The average scores on the NEI-VFQ 25 questionnaire of patients fitted with scleral lenses for at least 6 months were significantly higher than those without scleral lenses, with a global score of 80.2/100 with, versus 48.1/100 without, scleral lenses (P<0.0001). The global score increased by an average of 32.1±4.6 points (-28, 82) (P<0.0001). Statistical analysis found no significant difference in global score between patients in the keratoconus and keratoplasty groups (P>0.05). Scleral lenses showed a significant improvement in quality of life for patients who had failed or are intolerant to conventional rigid gas permeable contact lenses. In our two main optical indications, keratoconus and keratoplasty, they represent an alternative or a step prior to surgery.