Thanh Hoang-Xuan

Differential Expression of Extracellular Matrix Metalloproteinase Inducer (CD147) in Normal and Ulcerated Corneas Role in Epithelio-Stromal Interactions and Matrix Metalloproteinase Induction

Extracellular matrix metalloproteinase inducer (EMMPRIN) was originally identified on the tumor cell surface as an inducer of matrix metalloproteinase (MMP) production in neighboring fibroblasts. Here we demonstrate a role for EMMPRIN in MMP induction during corneal wound healing. MMP and EMMPRIN expression was analyzed in normal and ulcerated human corneas, as well as in corneal epithelial and stromal cells in culture using confocal microscopy, zymography, immunoblots, and real-time polymerase chain reaction. In normal cornea EMMPRIN was predominantly expressed in the epithelium but was markedly induced in the anterior stroma of ulcerated corneas. This coincided with MMP-2 induction that co-localized with EMMPRIN at the epithelio-stromal boundary. The role of epithelial-stromal interaction in MMP induction was investigated in an in vitro co-culture system and demonstrated an induction and co-localization of EMMPRIN and MMP-2 in the fibroblasts at the interface with epithelial cells. Direct contact of fibroblasts with EMMPRIN-containing purified epithelial cell membranes also induced MMP-1, MMP-2, and EMMPRIN and this was inhibited by a blocking anti-EMMPRIN antibody, suggesting that EMMPRIN was primarily responsible for this induction. These findings, and the up-regulation of EMMPRIN by epidermal growth factor and transforming growth factor-beta, demonstrate a role for EMMPRIN in wound healing and suggest that sustained local up-regulation of EMMPRIN and MMPs in chronic situations in which healing is delayed may lead to excessive matrix degradation and corneal melts.

Comparison of and correlation between anterior and posterior corneal elevation maps in normal eyes and keratoconus-suspect eyes

PURPOSE: To compare the anterior and posterior corneal elevation maps between keratoconus‐suspect eyes and normal eyes. SETTING: Rothschild Foundation, AP‐HP, University Paris VII, Hôpital Bichat Claude Bernard, Paris, France. METHODS: The anterior and posterior corneal surface elevations were analyzed and compared in 60 normal myopic patients and 48 keratoconus‐suspect patients. The anterior and posterior best‐fit sphere radii, central and thinnest corneal pachymetries, anterior and posterior aconic shape parameters (aconic radius, aconic asphericity, aconic toricity), and anterior and posterior elevation in the 1.0 mm radius zone were analyzed. The correlations between elevation and aconic shape parameters between the anterior and posterior surfaces were compared. RESULTS: The mean central and thinnest pachymetry values were significantly lower in keratoconus‐suspect eyes (P<.0001). Compared with normal eyes, keratoconus‐suspect eyes had significantly increased anterior toricity (P = .0002) and posterior toricity (P<.0001), more negative asphericity (P = .042), and higher posterior elevation (P<.0001). The correlation between aconic toricity and the anterior and posterior corneal surfaces was better in keratoconus‐suspect eyes than in normal eyes. Aconic asphericity and apical curvature were less correlated in keratoconus‐suspect eyes than in normal eyes. CONCLUSIONS: The posterior corneal elevation and the corneal thickness values were different in keratoconus‐suspect eyes. The correlation between the anterior and posterior corneal aconic shapes was between keratoconus‐suspect eyes and normal eyes.

Reliability of pachymetric measurements using orbscan after excimer refractive surgery

PURPOSE To assess the accuracy of pachymetric measurements using Orbscan (Bausch & Lomb, Rochester, NY) after laser in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK). DESIGN Prospective instrument validation study. PARTICIPANTS Seventy-nine nonoperated normal eyes, 84 eyes after LASIK, and 50 eyes after PRK. INTERVENTION Laser in situ keratomileusis or PRK. METHODS Central corneal thickness was measured using ultrasound and Orbscan II. The acoustic factor (AF) was adjusted, based on the results obtained in the normal eye group, to minimize the difference between ultrasound and Orbscan pachymetric values. MAIN OUTCOME MEASURES Central corneal thickness as measured by Orbscan and ultrasound pachymeter. RESULTS Using the adjusted AF, which was 0.946, the mean difference between Orbscan and ultrasonic pachymetric measurements was 0 +/- 17, 16 +/- 28, and 68 +/- 39 microm in the normal, LASIK, and PRK groups, respectively. The difference between all groups was statistically significant (P < 0.0001). CONCLUSIONS Orbscan pachymetric values may be underestimated and less accurate after LASIK and PRK.

Comparison of the efficacy and safety of valaciclovir and acyclovir for the treatment of herpes zoster ophthalmicus.

OBJECTIVE To compare the efficacy and safety of valaciclovir and acyclovir in immunocompetent patients with herpes zoster ophthalmicus. DESIGN A multicenter, randomized, double-masked study. PARTICIPANTS One hundred ten immunocompetent patients with herpes zoster ophthalmicus diagnosed within 72 hours of skin eruption were treated; 56 were allocated to the valaciclovir group and 54 to the acyclovir group. METHODS Patients randomized to the valaciclovir group received two 500-mg tablets of valaciclovir three times daily and one tablet of placebo twice daily. Patients in the acyclovir group received one 800-mg tablet of acyclovir five times daily and one tablet of placebo three times daily for 7 days. MAIN OUTCOME MEASURES Main outcome measures included the frequency, severity, and duration of ocular complications, patient reports of zoster-associated pain, and the outcome of skin lesions. Tolerance was also assessed on the incidence and types of adverse effects and changes in laboratory parameters. The analysis was mainly descriptive and performed on an intent-to-treat basis. RESULTS Ocular complications of herpes zoster ophthalmicus were similar in the valaciclovir and acyclovir treatment groups. The main complications were conjunctivitis (54% and 52%, respectively), superficial keratitis (39% and 48%, respectively for punctate keratitis; 11% in each group for dendritic keratitis), stromal keratitis (13% in each group), and uveitis (13% and 17%, respectively). The long-term outcomes of these ocular complications were favorable and similar in both treatment groups. Pain duration and severity and outcome of skin lesions were similar between groups. Most patients reported prodromal pain. After 1 month, 25% of patients in the valaciclovir group and 31% in the acyclovir group still reported pain. The percentage of patients experiencing postherpetic neuralgia decreased during follow-up. The tolerance to acyclovir and valaciclovir was comparable and considered good. The most frequent adverse events were vomiting and edema of the eyelids or face (3%-5%). Three serious adverse events not linked to the study drugs occurred. CONCLUSIONS Valaciclovir is as effective as acyclovir in preventing ocular complications of herpes zoster ophthalmicus, including conjunctivitis, superficial and stromal keratitis, and pain. Tolerability of the two drugs is similar, but the dosing schedule of valaciclovir is simpler.

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.

Scleritis in Relapsing Polychondritis: Response to Therapy

The authors reviewed the records of 11 patients with relapsing polychondritis associated with active scleritis and analyzed the immunopathologic characteristics of ocular tissue from three of these. Seven patients (63%) required cytotoxic drugs, alone or in combination with low-dose oral corticosteroids. Only one patient was treated successfully with systemic corticosteroids alone. Two patients were controlled with dapsone and one with an oral nonsteroidal anti-inflammatory drug. Dapsone, which has been reported to be effective in the treatment of relapsing polychondritis, did not control the destructive scleral inflammation in six (75%) of eight patients; two (50%) of four patients with diffuse anterior scleritis were controlled with this drug. Patients with nodular and necrotizing scleritis were controlled with azathioprine and cyclophosphamide, respectively. These data suggest that the ocular manifestations of relapsing polychondritis, especially nodular and necrotizing scleritis, are less amenable to treatment with systemic corticosteroids and/or dapsone and that more potent immunosuppressants (azathioprine and cyclophosphamide) may be required to treat these lesions successfully. Results of histologic and immunofluorescent examination of conjunctival and/or scleral biopsy specimens from three patients confirmed the vasculitic nature of the eye lesions in this disease.

Extracellular matrix metalloproteinase inducer/CD147 promotes myofibroblast differentiation by inducing α-smooth muscle actin expression and collagen gel contraction: implications in tissue remodeling

Extracellular matrix metalloproteinase inducer (EMMPRIN) is a cell surface glycoprotein enriched on tumor cells and normal epithelia. It is mainly known for its ability to induce matrix metalloproteinase production in fibroblasts following epithelial‐stromal interaction. We sought to examine whether EMMPRIN has a broader role promoting fibroblast‐to‐myofibroblast differentiation. Because α‐smooth muscle actin (αSMA) is considered a marker of this differentiation process, we analyzed the effect of EMMPRIN on its expression in corneal and skin fibroblasts by Western blots, immunocytochemistry, and a functional assay of collagen lattice contraction. Increasing EMMPRIN expression by cDNA transfection or by treatment with exogenously added recombinant EMMPRIN resulted in an up‐regulation of αSMA expression. EMMPRIN also increased the contractile properties of the treated fibroblasts as demonstrated by the immunohistochemical appearance of stress fibers and by the accelerated contraction of fibroblast‐embedded collagen lattices. Blocking EMMPRIN expression by small interfering RNA inhibited αSMA and collagen gel contraction induced not only by EMMPRIN but also by transforming growth factor‐β, a major mediator of myofibroblast differentiation that also regulated EMMPRIN expression. These findings, combined with the fact that EMMPRIN and αSMA colocalized to the same cells in the stroma of pathological corneas, expand on the mechanism by which EMMPRIN remodels extracellular matrix during wound healing and cancer. Huet, E., Vallee, B., Szul, D., Ver‐recchia, F., Mourah, S., Jester, J. V., Hoang‐Xuan, T., Menashi, S., Gabison, E. E. Extracellular matrix metal‐loproteinase inducer/CD147 promotes myofibroblast differentiation by inducing α‐smooth muscle actin expression and collagen gel contraction: implications in tissue remodeling. FASEB J. 22, 1144–1154 (2008)

Corneal hysteresis measured with the Ocular Response Analyzer® in normal and glaucomatous eyes

Purpose:  To identify differences in corneal hysteresis (CH) and central corneal thickness (CCT) between healthy and glaucomatous patients.

Oral Acyclovir for Herpes Zoster Ophthalmicus

BACKGROUND Reports on the natural history of herpes zoster ophthalmicus stress its high morbidity related to vicious scars on eyelids, ocular complications, and post-herpetic neuralgia. Early treatment with oral acyclovir is effective, but the optimal duration of treatment has not been defined. METHODS The authors performed a bicentric, prospective, randomized, double-masked study of 86 patients with acute herpes zoster ophthalmicus, within 72 hours of skin eruption, who received oral acyclovir (800 mg 5 times daily), either for 7 days (plus 7 days oral placebo) or for 14 days. All patients concomitantly received ophthalmic 3% acyclovir ointment; follow-up was at least 6 months. RESULTS Statistical analyses of subjective symptoms, skin lesions, and ocular complications showed no significant differences between the groups, suggesting that a 7-day course of treatment was sufficient. Drug tolerance was good. Pooled data from both groups corroborated earlier reports that prompt treatment with oral acyclovir reduces the severity of the skin eruption, the incidence and severity of late ocular manifestations, and the intensity of postherpetic neuralgia. At 6 months, late ocular inflammatory complications were seen in 29.1% of our 86 patients, versus 50% to 71% of untreated patients described by others. Only 13% of our patients experienced post-herpetic neuralgia, which in no case required the use of analgesics. CONCLUSION The authors believe it is not useful to prolong treatment with 800 mg of oral acyclovir 5 times daily for more than 7 days in herpes zoster ophthalmicus. This study confirms the efficacy of oral acyclovir not only against skin lesions and ocular complications, but also against postherpetic neuralgia in herpes zoster ophthalmicus.

Autologous Platelet Concentrate as an Adjunct in Macular Hole Healing: A Pilot Study

PURPOSE A pilot study was undertaken to assess the efficacy of autologous platelets in macular hole healing. PATIENTS AND METHODS Eight eyes of eight patients with stage 3 or 4 macular holes, two of which had failed to heal after previous vitrectomy and gas tamponade, were included. The procedure consisted of pars plana vitrectomy with removal of posterior cortical vitreous, stripping of associated epimacular membranes, 15% perfluoroethane-air tamponade, and instillation of autologous platelet concentrate onto the posterior pole. Strict postoperative facedown positioning was observed for 12 days. Postoperative evaluation included visual acuity measurement, biomicroscopic macular appearance and scanning laser ophthalmoscope examination. The follow-up period ranged from 3 to 13 months (mean, 7 months). RESULTS Of eight eyes, flattening of the surrounding retina and closure of the hole were achieved in seven (87.5%). Visual acuity improved two lines or more in four eyes (50%) Four eyes (50%) reached a postoperative visual acuity of 20/50 or more. Increased nuclear sclerosis was observed in six eyes (75%), and retinal detachment occurred in two eyes (25%). CONCLUSIONS Autologous platelet concentrate administered peroperatively in full-thickness macular holes seems to be a safe and effective adjunct to vitrectomy with removal of posterior hyaloid and gas tamponade. A larger multicenter randomized prospective study is underway to verify these encouraging results before advocating the use of autologous platelets in macular hole surgery.