Type 2 diabetes mellitus duration and obesity alter the efficacy of autologously transplanted bone marrow-derived mesenchymal stem/stromal cells.

Human bone marrow-derived mesenchymal stem/stromal cells (BM-MSCs) represent promising stem cell therapy for the treatment of type 2 diabetes mellitus (T2DM), but the results of autologous BM-MSC administration in T2DM patients are contradictory. The purpose of this study was to test the hypothesis that autologous BM-MSC administration in T2DM patient is safe and that the efficacy of the treatment is dependant on the quality of the autologous BM-MSC population and administration routes. T2DM patients were enrolled, randomly assigned (1:1) by a computer-based system into the intravenous and dorsal pancreatic arterial groups. The safety was assessed in all the treated patients, and the efficacy was evaluated based on the absolute changes in the hemoglobin A1c, fasting blood glucose, and C-peptide levels throughout the 12-month follow-up. Our data indicated that autologous BM-MSC administration was well tolerated in 30 T2DM patients. Short-term therapeutic effects were observed in patients with T2DM duration of <10 years and a body mass index <23, which is in line with the phenotypic analysis of the autologous BM-MSC population. T2DM duration directly altered the proliferation rate of BM-MSCs, abrogated the glycolysis and mitochondria respiration of BM-MSCs, and induced the accumulation of mitochondria DNA mutation. Our data suggest that autologous administration of BM-MSCs in the treatment of T2DM should be performed in patients with T2DM duration <10 years and no obesity. Prior to further confirming the effects of T2DM on BM-MSC biology, future work with a larger cohort focusing on patients with different T2DM history is needed to understand the mechanism underlying our observation.

[KID syndrome: pathogenesis of ocular lesions]. / Syndrome KID (Keratitis-Ichtyosis-Deafness): hypothèse pathogénique de l'atteinte oculaire.

KID is a rare ectodermal syndrome of unknown etiology. It is characterized by vascular keratitis (K), congenital ichthyosis (I) and neurosensorial deafness (D). We report the cases of three patients with KID syndrome who all had typical vascular keratitis responsible for photophobia and impaired visual acuity, and severe meibomian dysfunction associated with hyperkeratotic lid borders. The authors believe that meibomian dysfunction plays an important role in the pathogenesis of ocular lesions. Consequently, patients were treated with oral minocycline, topical steroids and artificial tears. This treatment proved to significantly reduce ocular discomfort.

Determination of corneal asphericity after myopia surgery with the excimer laser: a mathematical model.

PURPOSE: To determine the theoretical change of corneal asphericity within the zone of laser ablation after a conventional myopia treatment, which conforms to Munnerlyn's paraxial formula and in which the initial corneal asphericity is not taken into consideration. METHODS: The preoperative corneal shape in cross section was modeled as a conic section of apical radius R(1) and shape factor p(1). A myopia treatment was simulated, and the equation of the postoperative corneal section within the optical zone was calculated by subtracting the ablation profile conforming to a general equation published by Munnerlyn et al. The apical radius of curvature r(2) of the postoperative profile was calculated analytically. The postoperative corneal shape was fitted by a conic section, with an apical radius equal to r(2) and a shape factor p(2) equal to the value that induced the lowest sum of horizontal residuals and the lowest sum of squared residuals. These calculations were repeated for a range of different dioptric treatments, initial shape factor values, and radii of curvature to determine the change of corneal asphericity within the optical zone of treatment. RESULTS: Analytical calculation of r(2) showed it to be independent of the initial preoperative shape factor p(1). The determination of p(2) was unambiguous, because the same value induced both the lowest sum of residuals and the lowest sum of the squared residuals. For corneas initially prolate (p(1) < 1), prolateness increased (p(2) < p(1) < 1), whereas for oblate corneas (p(1) > 1), oblateness increased (p(2) > p(1) > 1) within the treated zone after myopia treatment. This trend increased with the increasing magnitude of treatment and decreased with increasing initial apical radius of curvature R(1). CONCLUSIONS: After conventional myopic excimer laser treatment conforming to Munnerlyn's paraxial formula, the postoperative theoretical corneal asphericity can be accurately approximated by a best-fit conic section. For initially prolate corneas, there is a discrepancy between the clinically reported topographic trend to oblateness after excimer laser surgery for myopia and the results of these theoretical calculations.

Ocular involvement in Epstein-Barr virus-associated T-cell lymphoma.

PURPOSE: To determine if serous retinal detachment may occur in a case of Epstein-Barr virus-associated T-cell lymphoma. METHODS: We examined a 51-year-old man who had recent loss of vision and poor general health. RESULTS: Ocular involvement consisted of bilateral serous retinal detachment and choroidal infiltrates. The diagnosis of lymphoma was made by liver biopsy. The course of the disease was fulminant. Postmortem histologic examination disclosed a massive infiltration of the choroid and hematopoietic organs by pleomorphic large T cells. Epstein-Barr virus was detected by in situ hybridization. CONCLUSION: Ocular involvement, including choroidal infiltrates and serous retinal detachment, may occur in Epstein-Barr virus-associated T-cell lymphoma.

An analysis of therapeutic decision making regarding immunosuppressive chemotherapy for peripheral ulcerative keratitis.

We reviewed our experience in the management of 47 patients (61 eyes) with peripheral ulcerative keratitis (PUK) to establish guidelines for appropriate indications to consider institution of systemic chemotherapy. Fifty-three percent of patients had a systemic disease as the etiology of PUK; one fourth of these were newly diagnosed as a result of meticulous history taking. The histologic demonstration of vasculitis in ocular tissue was the crucial step in deciding on chemotherapy in more than half of our patients. The presence of scleritis was highly associated with active vasculitis. Twelve of 14 patients with bilateral PUK required chemotherapy. Recommendations for an approach to therapy of PUK are presented.

Romberg's progressive hemifacial atrophy: an association with scleral melting.

We report the unusual case of a 43-year-old woman who presented with Romberg's progressive facial hemiatrophy and spontaneous scleral perforation in the ipsilateral eye, for which scleral grafting was performed. Histologic and ultrastructural examination of the scleral specimen revealed a noninflammatory lytic process. The location of the scleral loss, exactly on the line of the "en coup de sabre" atrophy, as well as the light microscopy and ultrastructural histopathologic findings suggest that the scleral destruction was a late manifestation of Romberg's disease.

Limbal conjunctival Langerhans cell density in ocular cicatricial pemphigoid: an indirect immunofluorescence study on Dispase-split conjunctiva.

PURPOSE: To evaluate limbal conjunctival Langerhans cell density in ocular cicatricial pemphigoid patients versus normal controls. Langerhans cells obviously play a major role in T-cell activation and are involved in corneal and conjunctival inflammatory diseases. METHODS: We used a protease (Dispase II) on inferior limbal conjunctival biopsies to separate the epithelium from the substantia propria and performed indirect immunofluorescence to analyze CD1a+ (a specific Langerhans cell surface antigen) cell density on flat-mounted epithelial sheets obtained from 30 normal controls and 11 patients presenting with ocular cicatricial pemphigoid. RESULTS: This technique was quick and reproducible. The mean Langerhans cell density in normal limbal conjunctiva was 272 +/- 37 cells/mm2. It was significantly higher in ocular cicatricial pemphigoid patients: 386 +/- 43 cells/mm2 (p = 0.001). CONCLUSIONS: Conjunctival Langerhans cell density in ocular surface inflammatory diseases can best be evaluated by indirect immunofluorescence, following epithelial sheet separation from the substantia propria, using Dispase II.

Immunohistopathologic testing in patients suspected of ocular cicatricial pemphigoid.

PURPOSE: Optimizing the sensitivity of immunopathologic methods in detecting target antigens in immune-mediated cicatrizing conjunctivitis. METHODS: Immunofluorescence was performed on normal and salt-split conjunctival biopsies in fifteen patients with clinical evidence of ocular cicatricial pemphigoid, and results were compared with immunoperoxidase, a technique thought to be more sensitive although more expensive and more difficult technically to perform. RESULTS: Ten of fifteen biopsies (67%) were positive when conventional and salt-split immunofluorescence results were combined. Four of eight patients with positive conventional immunofluorescence showed more marked immunofluorescence with the salt-split method. All patients were positive with immunoperoxidase (100%). CONCLUSION: Immunoperoxidase was more sensitive than conventional or salt-split immunofluorescence in detecting immunoreactant deposition along the basement membrane of the conjunctiva. Salt-split immunofluorescence demonstrated more intense staining of conjunctival samples when compared with conventional immunofluorescence, without however increasing the yield of positive biopsies. Finding solutions for the proper handling of conjunctival tissue in salt may improve the diagnostic yield of salt-split immunofluorescence.

Epidemiological considerations about retinal opportunistic infections in HIV-infected patients in France.

PURPOSE: To evaluate the evolution of the epidemiology of retinal opportunistic infections in HIV-infected patients from 1994 to 1997 and to assess the effect of HAART initiated in 1996. MATERIALS AND METHODS: Epidemiological prospective study using the data collected during ocular examinations of HIV-infected patients conducted in a single referral center specialized in HIV infection. RESULTS: From 1995 to 1997, the total number of examined HIV-infected patients and the incidence of retinitis related to CMV, VZV, tuberculosis, and toxoplasmosis decreased. The incidence of CMV retinitis, which was by far the most frequent ocular infection, fell from 6.2% to 1.2%. COMMENTS: The dramatic decrease in retinal opportunistic infections since 1996 may be related to the use of HAART. However, a close follow-up is still justified due to the increasing occurrence of resistance to protease inhibitors.

Uveitis in patients treated with intravenous cidofovir.

PURPOSE: To study the characteristics of uveitis occurring during intravenous cidofovir treatment for CMV retinitis in patients with AIDS. PATIENTS AND METHODS: We retrospectively studied ten cases (16 eyes) of uveitis in patients with CMV retinitis treated with intravenous cidofovir. All the patients had ophthalmologic examinations and, if required, fundus angiographies. The median follow-up was eight months. RESULTS: Uveitis occurred after a mean of 8.5 infusions of cidofovir (range 2-17). All ten patients were on protease inhibitors. The mean CD4+ cell count was 92 +/- 51/microl and the median viral load was 3.9 log. All the eyes with uveitis had healed CMV retinitis. The first examination of the involved eyes showed inflammation of the anterior chamber (100%), vitritis (50%), posterior synechiae (75%), and low intraocular pressure (94%). Uveitis did not relapse in the seven patients who stopped cidofovir, whereas it relapsed in two of the three patients who did not stop treatment. At the end of follow-up, permanent posterior synechiae were present in 69% of the involved eyes. COMMENTS: Cidofovir therapy necessitates slit-lamp surveillance, especially in patients on HAART. Cidofovir-related uveitis requires a local steroid treatment, but if possible, cidofovir should be withdrawn.

The effects of Rimexolone 1% in postoperative inflammation after cataract extraction. A double-masked placebo-controlled study.

AIM: A multicentre, randomized, placebo-controlled double-masked study was conducted to assess the efficacy and safety of Rimexolone 1% eye drops in reducing inflammation after cataract surgery and intra-ocular lens implantation. METHODS: Rimexolone 1% (124 patients) or placebo (58 patients) was given, four times a day for 14 days starting 22-34 hours after surgery. All patients also received tobramycin 0.3% four times a day for 7 days. The clinical signs of ocular inflammation were recorded on days 1, 3, 8, 15 and 17 or 18. RESULTS: Rimexolone 1% markedly decreased the mean inflammation severity scores, and the sum of clinical assessments of cells and flare in the anterior chamber compared with placebo at each assessment. In addition, the percentage of patients with no anterior chamber inflammation was significantly higher with Rimexolone 1% than with the placebo at each assessment. All these results were statistically significant. Intra-ocular pressure did not rise after treatment with Rimexolone 1%. CONCLUSIONS: The results suggest that Rimexolone 1% ophthalmic solution is an effective and safe steroidal anti-inflammatory agent for topical use following cataract surgery and intra-ocular lens implantation.

Management of silicone-induced cataract in AIDS patients treated for viral retinitis-associated retinal detachment.

BACKGROUND AND OBJECTIVE: To evaluate the outcome of cataract surgery for patients with acquired immunodeficiency syndrome (AIDS) who underwent vitrectomy and silicone tamponade for viral retinitis-associated retinal detachment. PATIENTS AND METHODS: The authors retrospectively reviewed the data of five AIDS patients (five eyes) who had cataract within a mean period of 4 months following vitrectomy and silicone oil tamponade for viral retinitis-associated retinal detachment. Phacoemulsification and implantation of a poly-methylmethacrylate posterior chamber intraocular lens were performed. The mean postoperative follow-up was 3 months. RESULTS: Neither silicone oil loss nor retinal redetachment were reported postoperatively. Visual acuity improved in two eyes and remained unchanged in one eye. Total blindness occurred in two eyes. CONCLUSION: Although cataract surgery in these eyes is a relative easy procedure and does not interfere with the retinal status, visual outcome remains poor because of possible postoperative optic atrophy.

[Three-dimensionnal representation and descriptive geometry of the pure spherical and pure cylindrical profiles of Excimer photoablation]. / Modélisation tridimensionnelle et géométrie descriptive des profils de photoablations sphériques et cylindriques pures au laser Excimer.

PURPOSE: To analyze the theoretical shape of the lenticules of corneal tissue ablated using Excimer laser for the correction of pure negative and positive spherical and cylindrical refractive errors, and to investigate the possible correlations between their spatial configuration and the clinical outcome for each procedure. METHODS: To obtain a theoretical three-dimensional representation of each ablated lenticule, we used software that performs boolean operations on three-dimensional virtual surfaces (Bryce 3D, Metacreation, Dublin, Ireland). The representation of the theoretical shape of the refractive lenticule etched by a given profile of ablation based on a paraxial model over a circular optical zone was obtained by performing appropriate Boolean operations between different preoperative and postoperative surfaces or elements. These operations were repeated to obtain the representation of the theoretical additional lenticule corresponding to the volume of tissue ablated to blend any abrupt optical zone edges with a constant slope. RESULTS: The lenticule corresponding to the negative spherical treatment had its maximum thickness in its center and no thickness at its edge, thus inducing a natural blend with the peripheral untreated cornea. The lenticule corresponding to the positive spherical treatment had its maximal thickness at the junction between the optical and transition zones, which are both circular. The lenticule corresponding to the negative cylindrical treatment had its maximal thickness along the flatter initial meridian and an elliptical transition zone contour. The lenticule corresponding to the positive cylindrical treatment had its maximal thickness at the edge of the optical zone along the initial flatter meridian, and no thickness at the perpendicular principal meridian. The transition zone is also elliptical. CONCLUSION: The basic characteristics of the lenticule corresponding to the pure negative spherical treatment could explain the lesser degree of postoperative refractive regression than that one occurring after pure positive spherical treatment and pure positive and negative cylindrical treatments. The characteristics of the lenticules corresponding to the negative and positive cylindrical treatments may also account for the substantial spherocylindrical coupling and regression, respectively commonly observed after such treatments. The three-dimensional representation of the lenticules ablated for the correction of pure spherical and cylindrical refractive errors may help to better understand the outcome of these procedures aimed at reshaping the anterior surface of the cornea.

[Medical treatment of ocular burns]. / Brûlures oculaires: traitement médical.

Chemical burns, especially alkali burns, can induce severe damage to the eye, not only of its surface, but also of its deep structures. Ocular chemical burns require urgent medical care and sometimes surgery. Medical management of chemical burns of the ocular surface includes controlling the inflammation of the underlying corneal stroma, preserving limbal vasculature, and restoring the limbal stem cell population if necessary, as early as the 3rd week following the injury, which sometimes also requires surgery consisting for the most part of amniotic membrane and/or limbal stem cell transplantation.

[Corneal abscess: therapeutic attitude based on microbiological testing]. / Abcès de cornée: attitude thérapeutique adaptée à l'enquête microbiologique.

PURPOSE: Bacterial corneal ulcers can affect the integrity of the eye and need therefore to be treated following strict rules. The authors present a prospective study on 15 bacterial corneal ulcers for which the initial treatment with topical fortified antibiotics was guided according to the results of Gram stain. MATERIAL AND METHODS: Gram positive cocci ulcers were treated with vancomycine (5 cases), Gram negative rod ulcers with gentamycine and ticarcilline (2 cases), and the association of these 3 antibiotics was used when no bacteria was found (8 cases). RESULTS: The results of the Gram stain and the culture were consistent in all the cases. Mean healing time was statistically significantly shorter when an infectious agent was found on Gram stain (13 days) than when not (23 days). CONCLUSION: These results suggest that the prognosis of bacterial corneal ulcers is enhanced when infectious agents are recovered and that the strategy of initiating an antibiotic therapy adapted to the gram stain results appears reliable and efficient. The successful outcome of this approach needs a perfect collaboration with the microbiologist.

[Schnyder's crystalline dystrophy. II. Association with genu valgum]. / Dystrophie cristalline de Schnyder. II. Association à un genu valgum.

The present study describes a family in which Schnyder's crystalline stromal dystrophy coexisted with genu valgum. One member, a woman, exhibited only the corneal dystrophy. She underwent a bilateral corneal graft and the buttons studied by light and electron microscopy were described in another report. Her daughter exhibited only genu valgum and her son had both disorders. It is to our knowledge the fourth report on the combination of Schnyder's dystrophy and genu valgum in the same family. The significance of this association and other associations like hyperlipoproteinaemia and xanthelasma are discussed.

[Keratitis in Lyme disease]. / Kératite dans la maladie de Lyme.

The authors report the case of a 15-year-old female suffering from bilateral keratitis revealing Lyme's disease, 6 years after a tick bite. The corneas disclosed multiple hazy infiltrates adjacent to the limbus and in the midperiphery, from the superficial layers to pre-Descemet's membrane. The other systems involved were the joints, the skin (an atypical erythema chronicum migrans), and perhaps the peripheral nerves. The diagnosis was confirmed by indirect immunofluorescence assays in the serum of the patient who completely and rapidly healed with amoxicillin and systemic and topical steroids. The clinical and serological pitfalls which explain the frequent delayed diagnosis of Lyme's disease, its complications, especially ocular, and the therapeutic strategies are discussed.

[A review of mathematical descriptors of corneal asphericity]. / Etude des paramètres permettant la description mathématique de l'asphéricite cornéenne.

PURPOSE: Corneal asphericity may be modeled on a conic section which can be described by the apical radius of curvature in the meridian studied and by a measure of the degree of asphericity. MATERIAL AND METHODS: Through an extensive review of the literature, we expose the principles, the population variations and report the application of such corneal modeling. RESULTS: The aspheric anterior corneal surface can be described by a conic section, defined by its radius of curvature and by a parameter measuring asphericity. We analyse the various parameters used in the literature to determine their usefulness. Conic sections, obtained by cutting a cone by a plane, include ellipses, hyperbolas and parabolas. Two useful parameters are the apical radius of the ellipse and its eccentricity defined in Cartesian terms by a second order equation where the apical radius is R and the eccentricity is e: The apical radius is that of the circle tangent to the apex of the conic section and e describes the variation of this curve with distance from the corneal apex. Baker introduced the form factor p making the equation: with It is easier to understand the effect of alteration of p than of e on corneal curvature: There is a relation between the horizontal, a, and the vertical, b, hemi-axes and R The advantage of this notation is that e(2) can be greater than 1 When p=0 the conic section is a parabola, when p<0 it is a hyperbola. Kiely et al. studied corneal asphericity by photokeratoscopy and introduced the parameter Q, where Q=p-1. Q, the asphericity factor, is used by the Eyesis and Orbscan systems; when Q=0 the cornea is spherical. Thus different parameters describe variations in corneal curvature along any meridian. Average anterior corneal asphericity using various keratometric systems is p=0.8, making the corneal section a prolate ellipse. However there is great individual variation, 20% of normals exhibiting oblate (p>1), paraboloid (p=0) or hyperbolic (p<0) corneas. all becoming more spherical with age. Little connection between asphericity and ametropia is reported, except for a tendency to flattening in myopia and towards oblateness in progressive myopia. Direct measurement of denuded cadaver corneas gave a prolate elliptical profile although calculation after deduction of epithelial thickness measured by ultrasonic biomicroscopy suggested p=-0.22, a hyperbolic profile. The few reports on the posterior surface suggest it to be hyperbolic or prolate. Increasing distance from the corneal apex worsens the comparison to a conic section as flattening increases. Precision can be improved by adding polynomial coefficients above the second degree to the equation of the section: The non-toric 3D corneal surface can be described by the following equation for the revolution of a conic section about the optic axis: x(2)+y(2)+pz(2)-2rz=0 where z is the axis of revolution. Since the mean value of p is 0.8 this corresponds to a sphere stretched along one axis, as is a rugby ball. Each meridian has the same radius of curvature and the value of p is constant. For a toric cornea the radius and value of p must be defined for two meridia at right angles. This corresponds to an elongation on an axis different from that of revolution. Similarly a toric ellipsoid is generated by rotation of an arc around an axis at right angles to its elongation. Because of its asphericity, representation of the corneal surface depends on the direction in which its curvature is measured: In the ellipsoidal model this depends on the principal meridians, the tangential, in the plane of the axis of symmetry and the saggittal, perpendicular to this. These may define two radii of curvature, the saggital (axial) and the tangential. Most algorithms assume these properties of ellipsoids. Asphericity is translated into variations in radius of curvature from apex to periphery, increasing for a flat periphery, decreasing for a steep one. Associated to toricity, it gives rise to the common butterfly pattern. Spherical aberration is minimal through a small pupil but becomes significant the larger the aperture, with deterioration of image quality. Raytracing allows analysis of the effects of non-axial rays. The mean value of Q, at -0.26 thanks to the naturally prolate asphericity of the cornea reduces spherical aberration by half. The relaxed form of the crystalline lens further reduces it by inducing the opposite spherical aberation to that of the cornea. This is important in accommodation and presbyopia. The use of an aspheric corneal surface in the schematic eye allows calculation of the ideal asphericity, which corresponds quite well with clinical findings. Radial keratotomy reverses the natural asphericity of the cornea. Photorefractive keratotomy (PRK) also changes asphericity, Q increasing to an oblate value. These changes might increase spherical aberration, explaining some postoperative deficiencies. Current excimer laser protocols ignore asphericity, relying on paraxial algorithms alone. New strategies to control asphericity in order to diminish spherical aberration may offer solutions. The original conic section models were made to improve the geometry of contact lenses. Understanding of asphericity is important in adaptation after refractive surgery. Modification of spherical aberration by contact lenses and corneal warpage induced by rigid lenses have also been studied. CONCLUSION: The approximation of the corneal surface by a conic section allows understanding of corneal asphericity and offers a quantitative description. This allows a more precise description of the corneal surface and of the genesis of certain optical aberrations of the eye.

[Triple procedure with phacoemulsification prior to grafting]. / Triple procédure avec phacoémulsification précédant la greffe.

We report a surgical technique which combines phacoemulsification and posterior chamber in the bag intra-ocular lens implantation before penetrating keratoplasty. This combined technique can only be performed in eyes with clear cornea. This technique seems to be safer during cataract extraction. We compared this combined procedure with the classical technique which associates manual extracapsular extraction and posterior chamber intra-ocular lens implantation and penetrating keratoplasty.