[Hyperbaric oxygen therapy and eye disease: Review of the literature]. / Oxygénothérapie hyperbare et maladies oculaires : une revue de la littérature.

Hyperbaric oxygen therapy consists of breathing 100% oxygen continuously or intermittently in a chamber at a pressure equal to or greater than 1.4 absolute atmospheres. Indicated for the emergency treatment of carbon monoxide poisoning and other medical-surgical pathologies such as gas embolism or necrotizing soft-tissue infections, various studies have shown a beneficial effect of hyperbaric oxygen therapy in certain ocular pathologies, notably of microcirculatory origin, such as central retinal artery occlusion or macular edema linked to retinal vein occlusions. In addition, hyperbaric oxygen might represent an alternative treatment for ocular quinine toxicity and might also be useful as an adjuvant to surgery and antibiotics in cases of periorbital necrotizing fasciitis. On the other hand, oxygen in high concentrations has toxic ocular effects due to the production of reactive oxygen derivatives.

[Biomechanics of the lamina cribrosa: A determining factor in glaucomatous neuropathy. A review of the literature]. / Biomécanique de la lame criblée : un facteur déterminant de la neuropathie glaucomateuse. Une revue de la littérature.

Glaucoma is a chronic optic neuropathy characterized by progressive sclero-laminar remodeling. The main factor at the origin of these deformations is the intraocular pressure (IOP), the effect of which varies according to the biomechanical properties of the individual lamina cribrosa (LC). In this environment, the LC represents a malleable zone of weakness within a rigid corneoscleral shell. It is a dynamic structure whose movements play a key role in the pathogenesis of glaucoma: displacing it posteriorly, in addition to contributing to the characteristic appearance of glaucomatous cupping, would increase constriction on the nerve fibers and the laminar capillaries. Often incorrectly considered permanent in adults, these deformations have a certain degree of reversibility, which is currently better characterized thanks to progress in imaging techniques. The occurrence of anterior displacement and laminar thickening following a reduction in IOP could thus constitute a good prognostic factor by reducing mechanical stress on this region. These changes would tend to reduce laminar pore tortuosity and shear forces, which are probably key mechanisms of axonal loss in glaucoma.

[Demodex and ocular surface disease]. / Demodex et pathologies de la surface oculaire.

Demodex is a saprophytic mite of the ocular adnexa, which can in certain circumstances proliferate on the skin of the face and on the eyelid margins. It is involved in facial rosacea (especially in the papulopustular form) and in the development or aggravation of anterior and/or posterior blepharitis or even keratoconjunctivitis, often in association with cutaneous lesions ; the pathophysiology is often multifactorial. Symptoms are non-specific, but the presence of cylindrical sleeves on the eyelashes is very suggestive of infestation, and certain techniques of biomicroscopic examination or imaging, such as confocal microscopy in vivo, allow direct visualization of the parasite. Parasitological examination of the eyelashes can confirm the diagnosis and can be improved by good sampling technique. Eyelid hygiene and oil-based ointments are the cornerstone of treatment. New specific treatments, in particular topical treatments based on tea tree oil, ivermectin, as well as pulsed light therapy and micro-exfoliation of the eyelid margin, can help to reduce the parasitic load and improve symptoms.

Evaluation of an eyelid warming device (Blephasteam) for the management of ocular surface diseases in France: the ESPOIR study.

INTRODUCTION: Eyelid hygiene, including massage and warm compresses, is an important part of the treatment and prevention of Meibomian gland dysfunction (MGD). Although effective, it requires active participation of the patient and lacks standardisation. Blephasteam is a medical device designed to warm and humidify the eyelid with heating glasses, in order to liquify meibum, thus relieving symptoms and preventing relapse. MATERIALS AND METHODS: The ESPOIR study (Evaluation of the Satisfaction of Patients with Management of Ocular Surface Diseases) presented herein was designed to evaluate the safety and efficacy of this medical device in patients with MGD. A total of 28 French centers participated in the study. One hundred and two patients presenting with symptomatic dysfunction or Meibomian-related dry eye underwent two sessions per day with the eyelid warming device and recorded diary entries on a number of parameters every 2 days for the first week and then weekly for the remaining 2 weeks. Patients were assessed on days 0 and 21. RESULTS: Symptomatology, as recorded on a visual analogue scale (VAS) by the investigator (the primary efficacy variable) was significantly (P<0.001) improved at the end of the study (59.97, 95% CI 55.64-64.30 vs. 39.71, 95% CI 34.78-44.65 on Days 0 and 21 respectively), as was the mean symptoms score (mean decrease of 19.93 ± 22.15 VAS units; P<0.001), hyperemia score (-1.57 ± 1.96 and -1.45 ± 1.85; P<0.001, in the worse and contralateral eye respectively), and quality of meibum (mean -4.03 ± 3.08; P<0.001 and -3.32 ± 3.20; P<0.01, in the worse and contralateral eye respectively). More than twice as many reported their symptoms had improved or disappeared compared with those whose symptoms had not changed or had worsened. Global symptomatology, as assessed by the patients, declined throughout the study, and a large majority of patients were satisfied or very satisfied with the treatment. Clear vision and blinking were not impaired during use of the eyelid warming device, which insures proper spreading of the tear film, and patients were able to continue daily activities such as reading and watching television. No adverse events were reported, and there were no changes in intraocular pressure or visual acuity. Safety was rated as satisfactory or very satisfactory by more than 95% of the investigators. CONCLUSION: The study suggests that the eyelid warming device is safe and effective in reducing ocular discomfort and symptoms in MGD.

RGTA-based matrix therapy in severe experimental corneal lesions: safety and efficacy studies.

Corneal alteration potentially leading to ulceration remains a major health concern in ocular surface diseases. A treatment that would improve both the quality and speed of healing and control the inflammation would be of great interest. Regenerating agents (RGTAs) have been shown to stimulate wound healing and modulate undesired fibrosis in various in vivo systems. We investigated the effects of RGTA-OTR4120(®) in a rabbit corneal model in order to assess its potential use in ocular surface diseases. First, we assessed its safety for 7 and 28 days using the Draize test criteria in healthy rabbit eyes; then, we investigated the effect of a single dose (50µl, 5µg) in an alkali-burned cornea model. Daily follow-up of clinical signs of healing was scored, and histology was performed at D7. RGTA was well tolerated; no signs of ocular irritation were observed. In the corneal alkali-burn model, non-RGTA-treated eyes showed inflammatory clinical signs, and histology confirmed a loss of superficial corneal layers with epithelial disorganization, neovascularization and infiltration of inflammatory cells. When compared to NaCl control, RGTA treatment appeared effective in reducing clinical signs of inflammation, enhancing re-epithelialization, and improving histological patterns: edema, fibrosis, neovascularization and inflammation. Three to four layers of epithelial cells were already organized, stroma was virtually unvascularized and keratocytes well implanted in parallel collagen fibers with an overall reorganization similar to normal cornea. RGTA appears to be a promising agent for controlling ocular surface inflammation and promoting corneal healing and was well tolerated. This study offers preclinical information and supports the findings of other (compassionate or pilot) studies conducted in patients with various ocular surface diseases.

[Efficacy assessment of Nutrilarm®, a per os omega-3 and omega-6 polyunsaturated essential fatty acid dietary formulation versus placebo in patients with bilateral treated moderate dry eye syndrome]. / Évaluation de l'efficacité du Nutrilarm®, complément nutritionnel à base d'acides gras essentiels polyinsaturés oméga 3 et oméga 6, versus placebo chez des patients atteints de sécheresse oculaire bilatérale modérée et traitée.

INTRODUCTION: Inflammation is one of the main mechanisms common to all forms of dry eye. Since polyunsaturated acids are known to show biological anti-inflammatory properties, the aim of this study was to evaluate the efficacy of dietary n-6 and n-3 fatty acids in patients suffering from ocular dryness. PATIENTS AND METHODS: One hundred and eighty-one patients diagnosed with bilateral moderate dry eye who were already treated with lachrymal substitutes were randomized in a double-blind international study to receive placebo or Nutrilarm(®) capsules (combination of omega-3 and omega-6), twice a day for 6 months. In all subjects, dryness feeling, overall subjective comfort, and ocular symptoms (burning, stinging, sandy and/or gritty sensation, light sensitivity, reflex tearing, and ocular fatigue) were evaluated at each visit. Furthermore, fluorescein tests (break-uptime and Oxford scheme) and lissamine green test were performed at each visit. The Schirmer test was performed at inclusion and after 6 months of treatment. RESULTS: After 6 months of supplementation with Nutrilarm(®), both the BUT scores and ocular fatigue were significantly improved when compared with placebo (P=0.036 and P=0.044, respectively). There was a trend in favor of Nutrilarm(®) in terms of the efficacy evaluated by the investigator (P=0.061). Fewer patients experienced a feeling of severe dryness with Nutrilarm(®) compared with placebo after 6 months of treatment (2.5 and 9.3%, respectively), but the difference was not statistically significant. CONCLUSION: Oral administration of a double supplementation dietary n-6 and n-3 fatty acids present an additional therapeutic advantage in patients suffering from ocular dryness who were already treated with lachrymal substitutes.

Cytoprotective effect against UV-induced DNA damage and oxidative stress: role of new biological UV filter.

The majority of chemical solar filters are cytotoxic, particularly on sensitive ocular cells (corneal and conjunctival cells). Consequently, a non-cytotoxic UV filter would be interesting in dermatology, but more especially in ophthalmology. In fact, light damage to the eye can be avoided thanks to a very efficient ocular antioxidant system; indeed, the chromophores absorb light and dissipate its energy. After middle age, a decrease in the production of antioxidants and antioxidative enzymes appears with accumulation of endogenous molecules that are phototoxic. UV radiations can induce reactive oxygen species formation, leading to various ocular diseases. Because most UV filters are cytotoxic for the eye, we investigated the anti-UV properties of Calophyllum inophyllum oil in order to propose it as a potential vehicle, free of toxicity, with a natural UV filter action in ophthalmic formulation. Calophyllum inophyllum oil, even at low concentration (1/10,000, v/v), exhibited significant UV absorption properties (maximum at 300nm) and was associated with an important sun protection factor (18-22). Oil concentrations up to 1% were not cytotoxic on human conjunctival epithelial cells, and Calophyllum inophyllum oil appeared to act as a cytoprotective agent against oxidative stress and DNA damage (85% of the DNA damage induced by UV radiations were inhibited with 1% Calophyllum oil) and did not induce in vivo ocular irritation (Draize test on New Zealand rabbits). Calophyllum inophyllum oil thus exhibited antioxidant and cytoprotective properties, and therefore might serve, for the first time, as a natural UV filter in ophthalmic preparations.

[Treating severe dry eye syndromes with autologous serum]. / Traitement des syndromes secs graves par sérum autologue.

BACKGROUND: Dry eye syndrome with tear deficiency can be improved with artificial tears, which can be associated with topical anti-inflammatory agents. Autologous serum can provide the ocular surface with beneficial growth factors and vitamins. PATIENTS AND METHODS: Twenty-one patients suffering from severe dry eye due to Sjögren's syndrome were treated with 20% autologous serum for 2 Months. The Schirmer I test, break-up time, and fluorescein and lissamine green stainings were performed before and after treatment. Subjective complaints such as burning, foreign body sensation, dryness and photophobia were assessed by a questionnaire as well as a face score reflecting the current condition of patients' eyes. RESULTS: Lissamine green and fluorescein scores improved significantly as well as subjective symptoms of burning, foreign body sensation and dryness (p<0.05). The face score was significantly improved. Bacterial culture of serum delivered to the patients all remained negative. DISCUSSION: Autologous serum provides growth factors and vitamins that are useful for an altered ocular surface due to Sjögren's disease. However, some problems still remain: risk of contamination, arbitrary dilution of autologous serum, and a current lack of regulations for use of autologous serum. A close collaboration between ophthalmologists and the Etablissement Français du Sang (French Blood Bank) is mandatory because autologous serum should be considered as a useful tool to treat severe ocular surface disorders. CONCLUSION: The use of autologous serum improved symptoms and objective signs caused by severe Sjögren's syndrome. Currently, a lack of clear regulations prevents its widespread use in severe ocular surface disorders.

[Use of brimonidine 0.2% in treatment of glaucoma or ocular hypertony after poorly tolerated beta-blocker treatment]. / Intérêt de la brimonidine 0,2% dans le traitement du glaucome ou de l'hypertension intraoculaire après intolérance à un traitement par beta-bloquant.

This study intended to evaluate the advantages of brimonidine tartrate 0.2% (Alphagan((R))), a selective alpha-2 receptor agonist, relaying a poorly tolerated beta-blocker treatment. Effectiveness, as assessed by intraocular pressure, local and general tolerance of the treatment, and the quality of life of the patients included in the study, was compared for these two eye drops. This multicenter and prospective study, performed by 450 ophthalmologists, included 807 adults presenting with glaucoma or ocular hypertony over 8 months. After a poorly tolerated beta-blocker treatment, which had started at least 6 months before, these patients received brimonidine over 8 weeks. At 3 successive visits, intraocular pressure, biomicroscopic examination results, and visual acuity were recorded. A quality-of-life questionnaire evaluating breathlessness, fatigue, depressive mood, loss of appetite, and satisfaction with the treatment was also given to patients. In the 731 patients observed in the study, the analysis concluded a statistically significant decrease in intraocular pressure (-2.5mmHg) and in the cardiovascular parameters during brimonidine treatment: blood pressure was reduced by 3mmHg and 1.1mmHg for systolic and diastolic pressure, respectively. The heart rate rose by 1.7 beats/min. The quality-of-life questionnaire revealed less breathlessness (-26%), fatigue (-24.9%), depressive mood (-19.3%), and better appetite (+8.2%). The feeling of satisfaction with the brimonidine treatment was significantly improved for 95 patients. However, 12% of all patients stopped their treatment because of adverse effects. Brimonidine improved the glaucomatous patients' quality of life, at least in some areas. Improved intraocular pressure could at least in part result from better compliance with the treatment. Brimonidine is an encouraging alternative after an unsatisfactory beta-blocker treatment.

Effects of EGb761 and superoxide dismutase in an experimental model of retinopathy generated by intravitreal production of superoxide anion radical.

BACKGROUND: A study was carried out to investigate the effect of two antioxidants--Ginkgo biloba extract (EGb761) and superoxide dismutase (SOD)--in an experimental model of vitreoretinopathy obtained by direct production of oxygen free radicals in the vitreous cavity. METHODS: Twenty-eight pigmented rabbits were used. Vitreoretinopathy was induced by intravitreal injection of 50 microliters of a mixture composed of 40 nmol of xanthine and 0.001 IU of xanthine oxidase. Rabbits were randomly distributed into four groups: Group 1 (n = 8) did not receive any treatment and served as a positive control. Groups 2 (n = 8) and 3 (n = 8) received for 1 month EGb761 given orally at a dose of 100 mg/kg/day, respectively 1 day after and 1 week before induction of retinopathy. Group 4 (n = 4) was treated by three intramuscular injections of 15,000 IU/kg of SOD, 24 h before induction and 24 and 48 h thereafter. Clinical evaluations and electroretinograms (ERG) were repeatedly performed until the animals were killed at day 28. Histological examinations and immunohistological procedures were performed to ascertain the origin and characteristics of the cellular proliferation and to compare vitreoretinal structures in the four groups. RESULTS: Intravitreal injection of xanthine-xanthine oxidase produced a strong inflammatory response with vitreous infiltrates and epiretinal membrane formation, inconstantly associated with retinal detachment. ERG showed a decrease of the a-, b- and c-waves beginning within a few hours after injection. Histologic evaluation found an intravitreal and epiretinal infiltration by leukocytes and epithelial-derived cells, dense vitreoretinal membranes and retinal detachments with occasional neovascularization. In the treated groups (groups 2-4), all clinical, electric and histologic data were significantly improved compared to the control group. However, no difference could be found among the three treated groups. CONCLUSION: This study demonstrates the strong pathologic effects of free radical production on the retina and the close relationships between free radicals, inflammatory pathways and vitreoretinal proliferative disorders. It also confirms the pharmacological interest of prevention by antioxidants and free radical scavengers.

Inhibition of preretinal proliferation by free radical scavengers in an experimental model of tractional retinal detachment.

An original model of experimental proliferative vitreoretinopathy consisting of an intravitreal injection of 10(7) human platelets and 1 IU of hyaluronidase was developed in pigmented rabbits. One group of 11 eyes served as non-treated controls. Two other groups of 11 eyes each received Ginkgo Biloba extracts which are known free radical scavengers (EGb761, Ipsen, France), given orally in two doses, 50 mg kg-1 day-1 and 100 mg kg-1 day-1 respectively, from the day after the platelet injection to the end of the first month. The fourth group (11 eyes) was intravenously injected with a unique dose of 15000 U kg-1 of superoxide dismutase the day after platelet injection. All animals were ophthalmoscopically examined in a masked fashion twice a week for 1 month and killed at the end of the experiment for histological analysis. Vitreoretinal proliferation was graded according to a six-stage classification. The non-treated eyes showed a high rate of retinal detachment (11/11 eyes), with a mean final score of 3.91 +/- 0.94. Histologic examinations consistently showed retinal retraction by fibrocellular preretinal membranes spreading to both surfaces of the retina as well as preretinal neovascularization. Many cells positively reacted with anti-cytokeratin or anti-vimentin monoclonal antibodies. All three groups of treated eyes showed significantly lower scores of vitreoretinal proliferation at almost each time point of examination. At the end of the study, five retinal detachments were found in the EGb761 group at 50 mg kg-1 day-1 (mean final score 2.45 +/- 1.37), only one in the group receiving 100 mg kg-1 day-1 (mean score 1.64 +/- 1.03), and one in the SOD treated eyes. The lowest mean score found at day 28 was observed in the group receiving SOD (1.36 +/- 1.43), although this group presented during the first 3 weeks with an intense vitreous and sometimes anterior chamber inflammation. Statistical comparison between treatments did not show significant differences at most time points of the study. These results demonstrate that antioxidants may efficiently prevent preretinal proliferation, in clinicopathological entities where free radicals had not yet been shown to play a direct pathogenetic role. They are also among the first attempts for inhibiting preretinal proliferations with non-cytotoxic agents and using a non-ocular route.

Influence of topical anesthesia on tonometric values of intraocular pressure.

The air pulse noncontact tonometer provides a safe and reliable method for measuring intraocular pressure (IOP), and makes it possible to avoid topical anesthesia. Based on previous reports that suggested possible anesthetic-induced IOP variations, this study was undertaken to investigate with this procedure the influence of local anesthetics on IOP and of some topically used drugs that could modify IOP values. In 212 normal or glaucomatous patients who underwent IOP measurement with a noncontact tonometer, IOP was determined before and in the first minutes following instillation of one of four tested drugs, oxybuprocaine and betoxycaine, two topical anesthetics currently used in applanation tonometry, and indomethacin suspension and metipranolol as controls. No significant effect was observed when comparing IOP values successively measured with the air pulse tonometer or 1 min after instillation of indomethacin suspension and metipranolol. In contrast a significant decrease in IOP was observed 1 and 5 min after instillation of one drop of the local anesthetics oxybuprocaine (mean IOP: 15.53 mm Hg before, 14.77 mm Hg at the 1st minute; p < 0.001) and betoxycaine (16.06 mm Hg before, 15.70 mm Hg at the 1st minute; p = 0.023). This effect was observed at least to the 15th minute, and in some patients, the decrease in IOP reached 8 mm Hg. Metipranolol only decreased IOP significantly at the 15th minute as compared to initial values, which differed from IOP variations following topical anesthesia. This phenomenon could not be related to mechanical effects of repetitive IOP measurements or massage by eyelids secondary to corneal irritation by anesthetic eye drops.(ABSTRACT TRUNCATED AT 250 WORDS)