Correlation between aqueous flare and chorioretinal neovascularization in age-related macular degeneration following intravitreal bevacizumab injections.

PURPOSE: Prospective evaluation of aqueous flare following intravitreal bevacizumab (Avastin, Genentech Inc., San Francisco, CA, USA) injections in eyes with choroidal neovascularization due to age-related macular degeneration. PATIENTS AND METHODS: Sixteen eyes of eight patients were recruited. Aqueous humor flare was determined by laser flare meter every month after one intravitreal injection of 1.25mg of bevacizumab at baseline followed by a second injection at month3 (day 100±21days). Four patients received an injection at month6 (±10days), and one patient received an injection at month7. RESULTS: Two months after the first intravitreal bevacizumab injection, flare values decreased from 10±5.57 (mean±standard deviation) to 5.2±1.69photon count/ms (P=0.0207) and from 8.3±3.59 to 5.4±0photon counts/ms, 2months after the second injection (P=0.02). CONCLUSION: Significantly decreased aqueous humor flare levels were noted after repeated injections of bevacizumab.

[A relevant choice for corticoid eye drops: solution or suspension?]. / Quel choix pour un collyre de corticoïdes : solution ou suspension ?

INTRODUCTION: The various forms of ophthalmic pharmaceutical presentation of steroids is proliferating on the market: solutions, gels, and suspensions. Suspensions are characterized by particles in solution and require agitation before instillation. This trial studied the impact of agitation on the corticoid concentration of eye drop solutions, gels, and suspensions. METHODS: Corticosteroid levels in a drop of a dexamethasone solution or suspension or betamethasone suspension or gel were compared using liquid chromatography. These levels were measured after shaking for 5, 10, 30s, and 1 min using a vortex or without shaking. RESULTS: The results of this study show that, whatever shaking time was used, the suspension form seems less suited to instillation of corticosteroids. The suspension did not deliver consistent levels of corticosteroids (mean between 23 and 99%) compared to solutions and gels, which released about 100% of the corticosteroid content in each drop. CONCLUSION: Physicians, ophthalmologists, and pharmacists should remind the patient of the proper use of these suspensions before instillation. In cases of treatment failure, it is necessary to check the instillation method before questioning patient compliance.

[Pilot study of a new matrix therapy agent (RGTA OTR4120) in treatment-resistant corneal ulcers and corneal dystrophy]. / Etude pilote d'un nouvel agent de thérapie matricielle (RGTA OTR4120) dans les ulcères de cornée et les dystrophies cornéennes rebelles.

AIMS: This study's objective was to evaluate the tolerance and safety of a new ophthalmic solution based on ReGeneraTing agent (RGTA) technology in a pilot noncontrolled exploration on compassion use for corneal ulcers and severe chronic dystrophies resistant to the usual treatments. RATIONALE: RGTAs are large biopolymers engineered to replace heparan sulfates specifically bound to matrix proteins and growth factors destroyed after a lesion has occurred. The RGTA-bound proteins are protected from proteolysis and this allows the extracellular matrix microenvironment to restore its original proper organization. The initial endogenous signals needed for tissues to regenerate are back on the restored matrix. They are expected to trigger the natural onset of events, signaling cells to migrate and multiply with the cascades and equilibrium found in tissue homeostasis. RGTA-induced matrix therapy is a possible alternative to cell or gene therapy in regenerative medicine. In a rabbit preclinical model of alkali-induced severe corneal ulcers, a single instillation of RGTA ophthalmic solution was found sufficient to enhance speed and quality of healing, restoring an almost normal corneal histology after only 1 week. These data prompted us to initiate this study. PATIENTS AND METHODS: Eleven eyes from ten patients were included in this study. All patients had severe dystrophic cornea or painful corneal ulcers rated over 50 on the VAS pain scale ranging from 0 to 100 and had undergone unsuccessful treatments. The RGTA ophthalmic solution was administered by the investigator during each weekly consultation as a single drop over 1 month. Tolerance and efficacy were judged on subjective criteria based on pain evaluation and functional inconvenience as well as on objective clinical criteria through a complete ophthalmic examination at days 3, 7, 14, 21, 28 and after 2 and 3 months from the beginning of the treatment. RESULTS: The study was conducted to completion for all patients included at the beginning. Tolerance was excellent both locally and generally: no uneasiness during instillation, no worsening of the initial pathology, no occurrence of ocular inflammation or increase in ocular pressure, and no general side effects were observed. In addition, we observed a noticeable analgesic effect, increasing with time and instillations, but pain reappeared in the majority of cases as treatment ended. The mean visual analog scale pain score was 72.73 +/- 7.86, it decreased significantly with the first drops of treatment. After 1 month, the mean visual analog scale pain score was 32+/-15.49, then it increased after the end of the treatment, confirming the link between the effects observed and the treatment. Efficacy on keratitis was moderate but with an overall tendency toward improvement. The initial Oxford Score was 3.37 +/- 1.06. After 1 month, it decreased significantly to 1.57 +/- 0.97 and then it rose again after the end of the treatment. As for corneal ulcers, of the five cases included, four healed during the protocol. Two reversed when the treatment stopped, two healed without reversion at the last follow-up visit. The last case was characterized by stem cell deficiency and no improvement was noted. It is important to keep in mind that these ulcers were all resistant to usual therapies. CONCLUSION: This RGTA ophthalmic solution is the first matrix therapy product in ophthalmology. The RGTA OTR4120 was used in treating chronic and severe corneal dystrophies as well as corneal ulcers resistant to usual treatments. It was very well tolerated with no side effects. It significantly reduced pain and favored corneal healing in almost all corneal ulcers. Weekly instillation of a single drop seems insufficient and these very promising data need to be confirmed on a larger population in a controlled trial with more adapted dosages. Based on these preliminary data, a RGTA-based matrix therapy product may be a very innovative solution to unresolved pain and corneal surface healing problems.

[Usefulness of voriconazole in treatment of Phoma glomerata after penetrating injury]. / Endophtalmie à Phoma glomerata après plaie du globe et efficacité du traitement par voriconazole en intravitréen.

We report the first case of endophthalmitis caused by Phoma glomerata. A 32-year-old man who underwent retinal detachment surgery consecutive to a penetrating globe injury presented with endophthalmitis 7 days after surgery. Anterior chamber tap and intravitreal injection of antibiotics (ceftazidime and vancomycin) were performed systematically. Fungus was observed at microscopic examination of the aqueous humor and treatment with intravitreal injection of amphotericin B was decided. The patient failed to improve with intravitreal amphotericin B but responded clinically to intravitreal voriconazole. The fungus was identified after culture as Phoma glomerata. The MIC for amphotericin B was 1microg/ml, for caspofungin was 2microg/ml, and for itraconazole was 8microg/ml or more. The MIC for voriconazole was up to 8microg/ml. The clinical response after intravitreal injection may be related to the high concentrations reached in the vitreous. Because of severity and ominous prognosis of intraocular fungal infections and posttraumatic Phoma ocular infections, aggressive management is required by intravitreal voriconazole administration.

[Macular hole surgery with and without infracyanine-green-guided removal of the internal limiting membrane]. / Chirurgie du trou maculaire avec et sans pelage de la limitante interne à l'aide du vert d'infracyanine.

PURPOSE: To investigate the possibility of an adverse effect of infracyanine-guided internal limiting membrane (ILM) removal on functional results of macular hole surgery. PATIENTS AND METHODS: A retrospective study of two consecutive groups of patients operated for macular hole between January 1998 and December 2001. In group 1 (21 patients), no attempt was made to remove the internal limiting membrane. In group 2 (21 patients), the ILM was peeled using infracyanine green (ICG). RESULTS: In group 1, 17 of 21 (81%) macular holes were closed by one surgery and 20 of 21 (95%) in group 2; however, this was not statistically significant. Mean preoperative visual acuity was close to 1 on the Logmar scale in both groups. Postoperative visual acuity was 0.6 in group 1 and 0.5 in group 2: four Snellen lines of improvement in group 1 and five lines in group 2. Postoperative visual acuity was the same or better in 16 of 21 patients in group 1 and in 18 of 21 in group 2. These differences were not statistically significant. Late reopening of the hole was statistically less frequent in group 2. Three cases of atrophic patterns at the level of foveal pigment epithelium were noted in each group as was one case of phototraumatism in group 1. These results were stable after more than 18 months of follow-up. All eyes became pseudophakic. CONCLUSION: In this study, infracyanine-guided removal of the internal limiting membrane did not significantly improve the results of macular hole surgery. No adverse effect of infracyanine on visual function or retinal toxicity was found and late reopening was less frequent.

[Cytotoxicity evaluation of different eyes drops with cyclosporine oral solution (Sandimmun)]. / Etude de la cytotoxicité de différents collyres à base de ciclosporine A buvable (Sandimmun).

INTRODUCTION: Cyclosporine is a molecule used in ophthalmology for the prevention of corneal graft rejection. The systemic use of this product can lead to serious adverse side effects that can be avoided using the topical formulation of cyclosporine. However, cyclosporine application can induce ocular irritation. MATERIAL AND METHODS: The aim of this study is to evaluate the cytotoxicity of four formulations of 2% cyclosporine eye drops: Sandimmum intravenous solution diluted with NaCl 0.9%, Sandimmun oral solution diluted in castor oil or corn oil after ethanol evaporation, and Sandimmun oral solution diluted in castor oil without previous ethanol evaporation. Two tests--the Draize test and the evaluation of cytotoxicity of adherent alive cells with cold light cytofluorimetry on microplates--were used in this study. RESULTS: These tests demonstrated that the aqueous solution shows more toxicity than the other formulations, and the type of oil and ethanol concentration influence cell viability. CONCLUSION: These results helped the Pharmacy unit choose the vehicles for a safe cyclosporine eye drop formulation and thus decrease the side effects of cyclosporine eye drop instillation with a decrease in ethanol concentration compared to published formulations.

[Tenotoxic potential of fluoroquinolones in the choice of surgical antibiotic prophylaxis in ophthalmology]. / Prise en compte du potentiel ténotoxique des fluoroquinolones dans le choix d'une antibioprophylaxie chirurgicale en ophtalmologie.

PURPOSE: Fluoroquinolones are mainly used in ophthalmic antibiotic prophylaxis because of their broad spectrum activity and good ocular diffusion. But a single oral dose of fluoroquinolones can result in a serious source of tendinopathy and tendon rupture, especially in patients 60 years and older. It seems very important to investigate tendon toxicity of fluoroquinolones to improve the risk-benefit ratio in ophthalmologic antibiotic prophylaxis. MATERIAL: and methods: The intrinsic tenotoxic potential of four fluoroquinolones (pefloxacin, ofloxacin, ciprofloxacin, levofloxacin) was directly evaluated on living adherent tendon cells in microplates. Cell viability and reactive oxygen species production was evaluated using neutral red, alamar blue, and dichlorofluorescin diacetate tests. RESULTS: Results showed a loss of viability associated with free radical production depending on fluoroquinolone molecules. Pefloxacin appeared more tenotoxic but no study has confirmed its efficacy in surgical antibiotic prophylaxis and its use in the patient who is 60 years and older could be disputed. Ciprofloxacin is highly toxic with a low ocular diffusion and seems to be inappropriate for antibiotic prophylaxis. Ofloxacin and levofloxacin are less cytotoxic, associated with good ocular diffusion and a broad antibacterial spectrum. CONCLUSION: Ofloxacin and levofloxacin seem to be good alternatives for improving the risk-benefit ratio in surgical antibiotic prophylaxis in patients 60 years and older.