mycophenolic-acid and Keratitis--Herpetic

The immune privileged nature of the cornea contributes to the favourable outcome in corneal grafts. However, preventive measures are necessary to reduce allograft rejection particular in "high-risk" cases. Although corticosteroids are still a major component of our immunopharmacological armentarium, they might be supplemented by other more specific immunomodulating agents. The spectrum includes agents such as azathioprin, methotrexate or more specific calcineurin inhibitors affecting T-cells (cyclosporin A, FK506) and highly selective monoclonal antibodies directed against T-cell subpopulations and other targets. In order to better evaluate the risks and benefit of these agents, the properties of established and forthcoming agents are presented. In addition, this review attempts to address some new concepts of tolerance induction following penetrating keratoplasty.

Topics: Adjuvants, Immunologic; Adrenal Cortex Hormones; Animals; Antiviral Agents; Azathioprine; Clinical Trials as Topic; Cyclosporine; Drug Therapy, Combination; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Keratitis, Herpetic; Keratoplasty, Penetrating; Methotrexate; Mice; Multicenter Studies as Topic; Mycophenolic Acid; Pilot Projects; Prospective Studies; Risk Factors; Sirolimus; Tacrolimus

The main reasons for graft failure following penetrating keratoplasty in patients with herpetic eye disease are recurrence of herpetic disease and allograft rejection. In a randomised trial the effect of systemic acyclovir and mycophenolate mofetil (MMF) on these post-keratoplasty complications was evaluated.. Patients with typical clinical findings of recurrent herpetic keratitis were enrolled in this single-centre study after contraindications to systemic immunosuppression were ruled out. In a prospective randomised trial 30 patients were treated in three groups. In group A patients received acyclovir 200 mg five times/day for 3 weeks. In group B patients were treated with acyclovir 200 mg five times/day for 1 year, and patients in group C received acyclovir 200 mg five times/day in combination with MMF 1 g twice daily for 1 year.. In group A 3 patients experienced seven herpes recurrences. One patient had a moderate and one further patient a severe allograft rejection. In group B three severe allograft rejections were observed. Herpes recurrences did not occur while receiving acyclovir prophylaxis, but only once after the prophylaxis had been stopped. In group C no herpes recurrence was observed, and only two mild allograft rejections occurred while being under combined acyclovir-MMF therapy. Another mild and one moderate allograft rejection were observed after cessation of MMF.. These results demonstrate that systemic acyclovir protects the grafts from recurrences of herpetic disease as long as it is administered at efficient doses. Simultaneously administered mycophenolate mofetil does not trigger herpes recurrences and protects the graft from severe allograft rejections, but mild, less dangerous immune reactions may still occur while receiving MMF. The combination of systemic acyclovir and mycophenolate mofetil therefore is recommended for patients at high risk for herpes recurrence and allograft rejections.

Topics: Acyclovir; Aged; Antiviral Agents; Drug Synergism; Drug Therapy, Combination; Female; Graft Rejection; Herpesvirus 1, Human; Humans; Immunosuppressive Agents; Keratitis, Herpetic; Keratoplasty, Penetrating; Male; Middle Aged; Mycophenolic Acid; Pilot Projects; Postoperative Complications; Prospective Studies; Recurrence; Virus Activation

Herpes simplex virus (HSV) infection is the most common cause of corneal blindness in developed countries. Penetrating keratoplasty is the only therapeutic option for visual rehabilitation in patients with severely scarred corneas. Recurrence of the underlying disease and allograft rejection (AR) are the common causes of graft failure. Systemic immuno-suppression with cyclosporin A is contraindicated due to the risk of HSV recurrence. The potent immunosuppressive properties of mycophenolate mofetil (MMF) have already been shown clinically. By reducing the intracellular guanosid-pool MMF inhibits the proliferation of lymphocytes. As these quanosin-nucleosides also act as competing substrates to acyclovir at the viral DNA-polymerase, a synergistic effect of MMF and acyclovir might be expected. The aim of this study was to evalute the efficacy and safety of a double-drug regimen with MMF and acyclovir in the prevention of acute allograft rejection and HSV recurrence following corneal transplantation.. Patients following penetrating keratoplasty due to herpetic eye disease have been treated with MMF 1 g twice dialy and acyclovir 5 x 200 mg/day for one year. Primary efficacy variables have been the number of acute AR and recurrence of herpetic disease per patient and time. The number of adverse events has been documented for safety analysis.. Fifteen patients have been enrolled. The average follow up period was 9.1 (+/- 5.2) months. No graft opacifications have been seen. With two AR and no recurrence of herpetic disease the efficacy ofthis therapeutic regimen was supperior compared with historical control groups.. In this first study on the efficacy and safety of a double drum regimen with acyclovir and MMF for the control of acute corneal AR and HSV-recurrenct following keratoplasty in patients with herpetic eye disease, the combination therapy has been shown to be a safe and highly efficient protocol for graft protection.

Topics: Acyclovir; Adult; Antiviral Agents; Drug Synergism; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Keratitis, Herpetic; Keratoplasty, Penetrating; Male; Middle Aged; Mycophenolic Acid; Pilot Projects; Secondary Prevention; Survival Analysis; Treatment Outcome

Keratitis due to herpes simplex infection is a common cause of corneal damage resulting in impaired vision.. The aim of this study was to assess the outcome of penetrating keratoplasties in patients treated with systemic antiviral and immunosuppressive drugs.. The authors retrospectively analysed data of 12 patients who underwent penetrating keratoplasty. The average age at onset of the first keratitis preceding surgery was 18 years (between 5 and 40 years). The indication for surgery in 9 cases was to improve vision and in 3 patient to prevent corneal perforation. Nine patients were given both acyclovir and mycophenolate mofetil, as anti-viral agent and immunosuppressive treatment, respectively. Two patients were treated with anti-viral agent only while one patient received no systemic therapy. The average follow-up time was 53.1 months (between 16 and 84 months).. Of the 9 patients who underwent surgery for improving vision, 8 patients had transparent grafts during follow up without vascularization. All eight patients had been treated with acyclovir and mycophenolate mofetil. In one patient who had no systemic treatment recurrence and graft rejection was observed. Only one of the surgeries performed in acute stage of inflammation resulted in a properly healed transparent graft without recurrence and rejection. In this patient acyclivir and mycophenolate mofetil therapy had been given previously. In two cases the preventive - full or partial - systemic treatment had no effect. The visual acuity improved in all cases. In three patients visual acuity was influenced by some other factors as well.. The systemic acyclovir and mycophenolat mofetil therapy is fairly successful in perforating keratoplasty due to herpes simplex infection. Acyclovir decreases the risk of recurrence, while mycophenolate mofetil may prevent graft rejection. The timing of surgery is decisive; it leads to better results when performed in a scarred, noninflammatory state.. Bevezetés: A herpes simplex vírus által okozott szaruhártya-gyulladás a leggyakoribb oka a cornea centrumában kialakuló hegnek, amely látásvesztést okozhat. Célkitűzés: A szerzők célul tűzték ki a perforáló keratoplasztika eredményességének felmérését a szisztémás antiherpeses és immunszuppresszív terápia alkalmazásának tükrében. Módszer: Perforáló keratoplasztikán átesett 12 betegen végezték a retrospektív randomizált vizsgálatot. A műtéti beavatkozásig eltelt idő az első keratitis megjelenésétől számítva átlag 18 év volt (5–40 év). A műtéti indikáció 9 esetben a látás javítása, 3 esetben a cornea perforációjának megelőzése volt. Szisztémás kezelésként 9 beteg herpeszvírus elleni (acyclovir) és immunszuppresszív (mycophenolat mofetil), 2 beteg csak herpeszvírus elleni kezelést kapott, egy betegnél nem alkalmaztak szisztémás terápiát. Az átlagos követési idő 53,1 hónap volt (16–84 hó). Eredmények: A látásjavító célú 9 műtét közül 8 esetben a transzplantátum átlátszóan, ereződés nélkül gyógyult. Mind a 8 beteg acyclovir és mycophenolat mofetil kezelésben részesült. Egy esetben – amikor a beteg szisztémás kezelést nem kapott – recidíva és rejectio is fellépett. Az akut gyulladásos tünetekben végzett műtétek közül egyben gyógyult a transzplantátum átlátszóan, recidíva- és rejectiomentesen; a beteg acyclovir és mycophenolat mofetil terápiában részesült. Két esetben recidíva és rejectio is fellépett. Ezek közül egyben a beteg acyclovir és mycophenolat mofetil, egyben csak acyclovirkezelést kapott. A látóélesség minden esetben javult, 3 esetben a látást egyéb tényezők befolyásolták. Következtetések: A szisztémás acyclovir és mycophenolat mofetil terápia sikerrel alkalmazható herpes simplex keratitisben végzett perforáló keratoplasztikák után. Az acyclovir csökkenti a recidívák számát, a mycophenolat mofetil a transzplantátum rejectióját. A műtét időpontjának megválasztása döntő; a gyulladásmentes, heges állapotban végzett műtétek jobb eredménnyel kecsegtetnek. Orv. Hetil., 2013, 154(52), 2065–2070.

Topics: Acyclovir; Adult; Aged; Antiviral Agents; Female; Graft Rejection; Humans; Immunosuppressive Agents; Keratitis, Herpetic; Keratoplasty, Penetrating; Male; Middle Aged; Mycophenolic Acid; Postoperative Period; Retrospective Studies; Treatment Outcome; Visual Acuity

Recurrence of herpetic keratitis and immune reactions is the major cause of graft failures after penetrating keratoplasty as a consequence of herpes simplex keratitis. No treatment regimen is yet considered a standard of care. This retrospective study analyzes the effectiveness of combined systemic acyclovir and immunosuppressive therapy with cyclosporine A (CSA) or mycophenolate mofetil (MMF) after high-risk keratoplasty in herpetic keratitis.. A total of 87 high-risk keratoplasties treated with postoperative combined systemic acyclovir and immunosuppressive therapy with CSA or MMF were analyzed retrospectively according to the therapeutic regimen, the degree of preoperative corneal vascularization, and tissue matching of the graft. Endpoints included immunological graft rejection, recurrence of the herpetic keratitis, graft failure, and visual acuity.. There was an overall trend toward an improvement of visual acuity. Graft failure occurred in 13.1%, in all cases after termination of immunosuppression with MMF or CSA. In 4 of 11 cases, immune reactions caused graft failure. Patients with 3 to 4 quadrants of corneal vascularization showed significantly higher rates of graft rejection than patients with 1 to 2 quadrants vascularized or avascular corneas. Herpetic recurrence occurred in 31.8% and caused 18.2% of graft failure. In 7 of 23 cases, graft rejection was induced by herpetic recurrence.. Graft survival rate and functional outcome after postoperative antiviral and immunosuppressive treatment in cases of penetrating keratoplasties after herpetic keratitis are comparable with results of normal-risk keratoplasties, despite existing high risks for immune rejections or herpetic recurrences.

Topics: Acyclovir; Adult; Aged; Aged, 80 and over; Antiviral Agents; Cyclosporine; Drug Therapy, Combination; Female; Follow-Up Studies; Graft Rejection; Humans; Immunosuppressive Agents; Keratitis, Herpetic; Keratoplasty, Penetrating; Male; Middle Aged; Mycophenolic Acid; Postoperative Care; Retrospective Studies; Secondary Prevention; Visual Acuity; Young Adult