Efficacy and safety of intravenous secukinumab in noninfectious uveitis requiring steroid-sparing immunosuppressive therapy.

PURPOSE: Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, exhibited promising activity in a proof-of-concept study when administered in intravenous (IV) doses to patients with active, chronic, noninfectious uveitis. This study compared the efficacy and safety of different IV and subcutaneous (SC) doses of secukinumab in patients with noninfectious uveitis. DESIGN: Multicenter, randomized, double-masked, dose-ranging, phase 2 clinical trial. PARTICIPANTS: Thirty-seven patients with active noninfectious intermediate uveitis, posterior uveitis, or panuveitis who required corticosteroid-sparing immunosuppressive therapy. METHODS: Patients were randomized to secukinumab 300 mg SC every 2 weeks for 4 doses, secukinumab 10 mg/kg IV every 2 weeks for 4 doses, or secukinumab 30 mg/kg IV every 4 weeks for 2 doses. Intravenous or SC saline was administered to maintain masking. Efficacy was assessed on day 57 (2-4 weeks after last dose). MAIN OUTCOME MEASURES: Percentage of patients with treatment response, defined as (1) at least a 2-grade reduction in vitreous haze score or trace or absent vitreous haze in the study eye without an increase in corticosteroid dose and without uveitis worsening or (2) reduction in corticosteroid dosages to prespecified levels without uveitis worsening. Percentage of patients with remission, defined as anterior chamber cell and vitreous haze scores of 0 or 0.5+ in both eyes without corticosteroid therapy or uveitis worsening. RESULTS: Secukinumab 30 mg/kg IV and 10 mg/kg IV, compared with the 300 mg SC dose, produced higher responder rates (72.7% and 61.5% vs. 33.3%, respectively) and remission rates (27.3% and 38.5% vs. 16.7%, respectively). Statistical and clinical superiority for the 30 mg/kg IV dose compared with the 300 mg SC dose was established in a Bayesian probability model. Other measures, including time to response onset, change in visual acuity, and change in vitreous haze score, showed numeric trends favoring IV dosing. Secukinumab, administered in IV or SC formulations, appeared safe and was well tolerated. CONCLUSIONS: Intravenous secukinumab was effective and well tolerated in noninfectious uveitis requiring systemic corticosteroid-sparing immunosuppressive therapy. Greater activity with IV dosing suggests that patients may not receive sufficient drug with SC administration. High-dose IV secukinumab may be necessary to deliver secukinumab in therapeutic concentrations.

Secondary graft failure and repeat endothelial keratoplasty after Descemet's stripping automated endothelial keratoplasty.

OBJECTIVE: To identify the causes of secondary graft failure after Descemet's stripping automated endothelial keratoplasty (DSAEK) and to evaluate the clinical outcomes of repeat endothelial keratoplasty (REK) in this patient population. DESIGN: Retrospective case series. PARTICIPANTS: Patients of a private practice Price Vision Group in Indianapolis, Indiana. METHODS: An initial consecutive series of primary DSAEK procedures performed by a single surgeon between October 2004 and December 2008 was reviewed to identify reasons for and outcomes of REK. MAIN OUTCOME MEASURES: Visual acuity and causes of secondary graft failure. RESULTS: In a consecutive series of 1050 primary DSAEK procedures, REK for secondary graft failure was performed in 37 eyes (3.5%). The most common reason for REK in this group was unsatisfactory visual acuity relative to the anticipated vision potential (n = 28/37; 76%). Unsatisfactory visual acuity was associated with abnormalities of donor tissue within the pupillary area, including wrinkles or folds, irregular graft thickness, and opacity in the interface. In the 28 eyes with unacceptable visual acuity after initial DSAEK, the median best spectacle-corrected visual acuity (BSCVA) before and after REK was 20/60 (range, 20/40-20/400) and 20/30 (range, 20/20-20/100), respectively, and 75% had BSCVA 20/40 or better after REK. The mean corneal thickness in the 28 eyes regrafted for unsatisfactory vision before and after REK was 809 µm (range, 642-979 µm) and 657 µm (range, 549-801 µm), respectively. Secondary graft failure caused by endothelial decompensation was the reason for repeat endothelial graft in the remaining 9 eyes (9/37; 24%). Eight eyes had a history of glaucoma, and 6 of them had glaucoma surgery. An episode of immune rejection reaction was documented in 6 of 9 eyes with endothelial decompensation. CONCLUSIONS: Our data suggest that the most common reason for REK after DSAEK is unsatisfactory vision. Patient and physician expectations for visual acuity are higher with DSAEK compared with penetrating keratoplasty. Repeat endothelial keratoplasty can provide improved vision in selected patients.

Influence of original flap creation method on incidence of epithelial ingrowth after LASIK retreatment.

PURPOSE: To compare the rate of epithelial ingrowth after LASIK retreatment among eyes with flaps created by femtosecond laser and those created by mechanical microkeratome. METHODS: Postoperative results from 272 consecutive LASIK retreatments performed by a single surgeon over a 4-year period were reviewed retrospectively to identify cases that developed clinically significant epithelial ingrowth, defined as that which required surgical removal. Flaps for the original LASIK treatments were created using a mechanical microkeratome or femtosecond laser. The same technique to lift the flap at the time of retreatment was used in all eyes included in this study. RESULTS: LASIK retreatment was performed in 132 eyes that had the initial flap created using a mechanical microkeratome (microkeratome group). Epithelial ingrowth was identified in 11 eyes of 9 patients. Surgical intervention to remove the epithelium from the stromal interface was required in 8 (6.1%) eyes. Femtosecond laser was used to create the initial LASIK flap in 140 eyes that required retreatment (femtosecond group). Epithelial ingrowth after LASIK retreatment was identified in 2 eyes of 1 patient in the femtosecond group (P=.004). Neither of these 2 eyes required surgical intervention to remove the epithelium from the stromal interface (P=.017). CONCLUSIONS: Eyes with femtosecond laser-created flaps may be less likely to develop significant epithelial ingrowth after LASIK retreatment when compared with eyes in which the flap was created using a mechanical microkeratome. The difference in rate of epithelial ingrowth may be related to the geometry of the flap edge.

Infliximab therapy for the treatment of refractory ocular inflammatory disease.

OBJECTIVE: To report the outcomes of infliximab therapy in the treatment of ocular inflammatory disease refractory to traditional immunomodulatory therapy (IMT). METHODS: We retrospectively reviewed the medical records of 27 patients. All patients had noninfectious ocular inflammatory disease refractory to traditional IMT and received 5 mg/kg of infliximab at 2-week to 8-week intervals. Main outcome measures were clinical response, reduction in concomitant IMT, and adverse effects. Cumulative incidences of inflammation control and vision change were calculated using life-table methods. RESULTS: Twenty-one patients experienced sustained improvement in inflammation with their initial course of infliximab therapy. Cumulative incidence of inflammation resolution at 12 months was greater than 90%. Sixteen patients were able to decrease the dose of their concomitant IMT medication or stop all other IMT. Four patients were able to discontinue all other IMT while receiving infliximab therapy. Three patients with scleritis were eventually able to remain inflammation-free while not taking any medication. At 12 months, 56% and 65% of left and right eyes, respectively, showed visual acuity improvement by 2 or more Snellen lines. Only 1 patient developed an adverse event requiring therapy discontinuation. CONCLUSIONS: We found a high rate of ocular inflammation control with infliximab therapy. The incidence of adverse effects in this study was low.

Chronic cicatrizing conjunctivitis in a patient with epidermolysis bullosa acquisita.

OBJECTIVE: To describe a nonconventional diagnostic technique used to diagnose a case of cicatrizing conjunctivitis associated with epidermolysis bullosa acquisita. METHODS: Direct immunofluorescence of a biopsy specimen of the patient's conjunctiva was performed using fluorescein-conjugated rabbit antihuman antibodies against IgA, IgG, and IgM; complement C3; and fibrinogen. Immunoblot assay using healthy human skin as substrate was performed to investigate for the presence of antibodies in the patient's serum. After the diagnosis of systemic autoimmune disease was established, intravenous immunoglobulin therapy was administered. RESULTS: Direct immunofluorescence of the conjunctiva revealed linear deposition of IgA and IgG, and C3 at the epithelial basement membrane zone. Immunoblot analysis demonstrated the presence of IgG antibodies in patient serum directed against a 290-kDa protein in human skin. A diagnosis of epidermolysis bullosa acquisita was established. All signs and symptoms improved dramatically 4 months after initiation of intravenous immunoglobulin therapy and remained stable during follow-up. CONCLUSIONS: Epidermolysis bullosa acquisita can manifest in the eye as chronic cicatrizing conjunctivitis indistinguishable from ocular cicatricial pemphigoid. A nonconventional diagnostic tool (immunoblot assay) might be helpful in establishing the diagnosis of an underlying systemic autoimmune disease in patients with chronic cicatrizing conjunctivitis. Intravenous immunoglobulin therapy was effective against chronic cicatrizing conjunctivitis associated with epidermolysis bullosa acquisita.

Long-term follow-up of patients with birdshot retinochoroidopathy treated with corticosteroid-sparing systemic immunomodulatory therapy.

PURPOSE: To evaluate the outcomes of patients with birdshot retinochoroidopathy (BSRC) treated with corticosteroid-sparing systemic immunomodulatory therapy (IMT). DESIGN: Retrospective, noncomparative, interventional case series. PARTICIPANTS: Thirty-five patients with BSRC evaluated at the Ocular Immunology and Uveitis Service of the Massachusetts Eye and Ear Infirmary from 1980 through 2003. METHODS: Data on age, gender, follow-up time, delay to diagnosis or referral, treatment before and during follow-up, complications of BSRC or treatment, Snellen visual acuities (VAs), and electroretinograms (ERGs) were recorded from patient charts. MAIN OUTCOME MEASURES: Disease progression as determined by Snellen VAs and serial ERGs, ocular complications of BSRC or corticosteroids, and complications of systemic IMT. RESULTS: Twenty-eight patients with a mean follow-up of 81.2 months were included. None of the patients had sufficient control of their inflammation before referral. All patients were treated with corticosteroid-sparing systemic IMT at some point during their follow-up: 92.9% were treated with cyclosporine, 67.9% with mycophenolate mofetil, 17.9% with azathioprine, 10.7% with oral methotrexate, and 7.1% with daclizumab. Ocular complications of BSRC and/or corticosteroids were cataract (53.6%), cystoid macular edema (35.7%), glaucoma (21.4%), epiretinal membrane (10.7%), and retinal detachment (3.6%). Average Snellen VAs at the time of initial visit were 0.64 (right eye) and 0.59 (left eye). Average final Snellen VAs were 0.74 (right eye) and 0.71 (left eye). (Logarithm of the minimum angle of resolution equivalents were -0.23, right eye initial; -0.19, right eye final; -0.38, left eye initial; and -0.31, left eye final.) In the right eye, 78.6% of patients and, in the left eye, 89.3% of patients had either the same or improved VA at the end of the follow-up. The 30-hertz flicker implicit time was prolonged in 58.3% of initial ERGs and in 62.5% of final ERGs. The bright scotopic amplitude was abnormal in 45.5% of initial and final ERGs. CONCLUSIONS: Long-term preservation of visual function is attainable with systemic corticosteroid-sparing IMT for patients with BSRC. Prompt treatment with systemic IMT may offer the best hope of maintaining retinal function in what is often thought of as a chronically progressive disease resistant to treatment.

Safety and efficacy of intravitreal triamcinolone acetonide for uveitic macular edema.

BACKGROUND: To evaluate the safety and efficacy of intravitreal triamcinolone acetonide (TA) for treating macular edema secondary to non-infectious uveitis. METHODS: Retrospective review of sixteen patients (20 eyes) with chronic cystoid macular edema (CME) as a consequence of controlled intermediate uveitis, posterior uveitis, or panuveitis who received at least one intravitreal injection of TA. Main outcome measures were visual acuity (VA), intraocular pressure (IOP), formation or progression of an existing cataract, and CME resolution during the follow-up period. RESULTS: At last follow-up, VA showed improvement (compared to baseline) in 11 eyes (55%), deterioration in three eyes (15%), remained completely unchanged in one eye (5%), and showed improvement initially but returned to baseline levels in five eyes (25%). At last follow-up, CME had relapsed or was still present in 10 of the eyes (50%). The remaining eyes showed complete resolution of the CME, without evidence of recurrence during the follow-up time. Mean VA at last follow-up showed statistically significant improvement (p = 0.02) in nonvitrectomized eyes (mean baseline VA: 1.14 +/- 0.58; mean final VA: 0.96 +/- 0.66) compared to the almost unaltered mean visual acuity for vitrectomized eyes (mean baseline VA: 0.76 +/- 0.41; mean final VA: 0.71 +/- 0.48)(p = 0.40, paired samples t-test). Elevation of IOP was transient in all cases and responded well to topical medications, except for one patient who required placement of an Ahmed valve. Preexisting cataract progressed in three of the 15 phakic eyes (20%). One patient developed a retinal detachment and required additional surgery to reattach it. Patients were followed for a mean of 34 weeks (median: 32 weeks; range: 19-56 weeks). CONCLUSIONS: Intravitreal TA may play a role in the treatment of uveitis-related CME. Further controlled studies are necessary to test this hypothesis.

The cell-layer- and cell-type-specific distribution of GalNAc-transferases in the ocular surface epithelia is altered during keratinization.

PURPOSE: It has been hypothesized that the biosynthesis of O-linked glycans on proteins, particularly on the highly O-glycosylated mucins, by the corneal and conjunctival epithelium is necessary for the protection and maintenance of a healthy ocular surface. The initial step in O-glycosylation is the enzymatic addition of N-acetyl galactosamine (GalNAc) to serine and threonine residues by a large family of polypeptide GalNAc-transferases (GalNAc-Ts). The purpose of this study was to determine the cellular distribution of GalNAc-Ts in the normal ocular surface epithelia and to compare their distribution with that in pathologically keratinized conjunctival epithelia. METHODS: Five conjunctival biopsy specimens and 5 corneas from normal individuals, and 14 conjunctival specimens from patients with ocular cicatricial pemphigoid (OCP) were used. Based on the histologic characteristics of their epithelia, OCP specimens were divided into two groups: less advanced, nonkeratinized (n = 6), and late-stage, keratinized (n = 8). Five monoclonal antibodies raised against the GalNAc-T1, -T2, -T3, -T4, and -T6 isoenzymes, were used for immunofluorescence microscopic localization according to standard protocols. RESULTS: Immunohistochemical studies revealed the presence of GalNAc-T2, -T3, and -T4 isoforms within the stratified epithelium of the cornea and the conjunctiva. The GalNAc-T4 isoenzyme was found in the apical cell layers, whereas GalNAc-T2 was found in the supranuclear region of the basal cell layers of both cornea and conjunctiva. GalNAc-T3 was distributed throughout the entire ocular surface epithelium, whereas GalNAc-T1 was found in scattered cells in conjunctiva only. Binding of antibody to GalNAc-T6 was restricted exclusively to conjunctival goblet cells. There were distinct alterations in expression patterns of GalNAc-T2, -T6, and -T1 in nonkeratinized OCP epithelia compared with normal epithelia. Both GalNAc-T2 and -T6 were expressed in the apical stratified epithelia, and T1 was detected in all cell layers in five of six biopsy specimens. By comparison with nonkeratinized OCP epithelia, a marked reduction in the binding of GalNAc-T antibody was observed in the late-stage keratinized conjunctival epithelia of patients with OCP. In all samples, apical GalNAc-T2 was absent, and GalNAc-T6 was entirely absent. Only one of eight samples was positive for GalNAc-T1. CONCLUSIONS: The presence of GalNAc-T isoenzymes in the human corneal and conjunctival epithelia is cell-layer and cell-type specific. The increased distribution of GalNAc-Ts observed in early stages of the keratinization process in patients with OCP suggests a compensatory attempt of the ocular surface epithelium to synthesize mucin-type O-glycans to maintain a wet-surface phenotype. This early increase in isoenzymes in nonkeratinized OCP epithelia is reduced as keratinization proceeds in the disease.

Relapsing polychondritis: a clinical review.

OBJECTIVE: This study comprehensively reviews the literature related to relapsing polychondritis (RP). METHODS: A detailed search via MEDLINE (PubMed) was performed using relapsing polychondritis as the key term. Relevant articles were analyzed with a focus on history, epidemiology, etiology, pathogenesis, clinical manifestations, diagnosis, treatment, and prognosis of RP. RESULTS: RP is a rare episodic and progressive inflammatory disease of presumed autoimmune etiology first described in 1923. RP affects cartilage in multiple organs, such as the ear, nose, larynx, trachea, bronchi, and joints. In addition, it can affect proteoglycan-rich tissues, such as the eyes, aorta, heart, and skin. The diagnosis of RP is based on the presence of clinical criteria. A standardized therapeutic protocol for RP has not been established. Nonsteroidal anti-inflammatory drugs, dapsone and/or colchicine, may control disease activity in some patients. In other patients, immunosuppressive drugs and prednisone have been effective. RP is a potentially lethal disease; pulmonary infection, systemic vasculitis, airway collapse, and renal failure are the most common causes of death. Earlier studies indicate survival rates between 70% at 4 years and 55% at 10 years. In a recent study, a survival rate of 94% at 8 years may be due to improved medical and surgical management. CONCLUSIONS: RP is a rare, multisystemic, and potentially fatal disease. The pathogenesis and optimal therapeutic approach to patients with RP is poorly understood.

Pars plana vitrectomy versus immunomodulatory therapy for intermediate uveitis: a prospective, randomized pilot study.

PURPOSE: Comparison of pars plana vitrectomy (PPV) with immunomodulatory therapy (IMT) for patients with intermediate uveitis (IU). METHODS: A prospective, randomized pilot study was performed on patients with recalcitrant IU associated with degradation of visual acuity (VA) despite standard treatment. Outcome measures (VA, intraocular pressure, anterior chamber and vitreous cellular infiltrate) were collected. RESULTS: Sixteen patients (18 eyes) were randomized to the PPV IMT group. Nine of 11 eyes (82%) treated with PPV showed resolution of inflammation at follow-up, at 5.93 years. Four of 7 eyes (57%) given IMT had persistent inflammation requiring subsequent PPV. PPV patients showed greater improvement in Snellen line, IOP, and vitreous cell reduction. Three PPV patients had cystoid macular edema (CME) initially; all resolved postoperatively. CME improved in 2 of 3 eyes using IMT. CONCLUSIONS: A higher percentage of patients treated with PPV had improvement of uveitis compared to those given IMT. A multicentered clinical trial is needed to confirm and statistically validate these conclusions.

Stevens-Johnson syndrome and toxic epidermal necrolysis: a review of the literature.

OBJECTIVE: To perform a comprehensive review of Stevens-Johnson syndrome and toxic epidermal necrolysis. DATA SOURCES: A MEDLINE search was performed for the years 1975 to 2003 using the keywords Stevens-Johnson syndrome and toxic epidermal necrolysis to identify relevant articles published in English in peer-reviewed journals. STUDY SELECTION: All clinical studies that reported on 4 or more patients, review articles, and experimental studies that concerned disease mechanisms were selected and further analyzed. Clinical reports that included fewer than 4 patients were selected only if they were believed to carry a significant message about disease mechanism or therapy. RESULTS: Stevens-Johnson syndrome and toxic epidermal necrolysis seem to be variants of the same disease with differing severities. A widely accepted consensus regarding diagnostic criteria and therapy does not exist at present. Despite the recent experimental studies, the pathogenic mechanisms of these diseases remain unknown. Although progress in survival through early hospitalization in specialized burn units has been made, the prevalence of life-long disability from the ocular morbidity of Stevens-Johnson syndrome and toxic epidermal necrolysis has remained unchanged for the past 35 years. Further progress depends on modification of the acute phase of the disease rather than continuation of supportive care. The available published evidence indicates that a principal problem in the pathogenesis is immunologic and that immunomodulatory intervention with short-term, high-dose intravenous steroids or intravenous immunoglobulin holds the most promise for effective change in survival and long-term morbidity. CONCLUSIONS: The results of this review call for a widely accepted consensus on diagnostic criteria for Stevens-Johnson and toxic epidermal necrolysis and multicenter collaboration in experimental studies and clinical trials that investigate disease mechanisms and novel therapeutic interventions, respectively.

Long-term progression, prognosis, and treatment of patients with recurrent ocular manifestations of Reiter's syndrome.

PURPOSE: To investigate the spectrum of ocular involvement, to examine the clinical outcome, and to analyze the influence of treatment in patients with chronic ocular manifestations of Reiter's syndrome (RS) referred to a tertiary care ocular immunology service. DESIGN: Retrospective, noncomparative, interventional case series. PARTICIPANTS: Twenty-five patients with RS evaluated at the Ocular Immunology and Uveitis Service of the Massachusetts Eye and Ear Infirmary from 1981 through 2001. METHODS: Charts of patients were reviewed and data on age, gender, follow-up time, ocular symptoms, extraocular involvement, ocular complications, therapy, and visual acuities were recorded. MAIN OUTCOME MEASURES: Visual acuity, ocular complications, disease progression, clinical outcome, and systemic treatment. RESULTS: Twenty-five patients (20 male and 5 female) diagnosed with RS, with a mean age at presentation to our service of 37 years, were studied. The mean follow-up was 48.5 months. Eighty-five percent of patients tested were positive for human leukocyte antigen B27. Sixty-four percent of patients had a positive family history. All patients had oligoarthritis and enthesitis, most commonly affecting the back (56%), Achilles tendon (52%), and sacroiliac joint (24%). Eighty percent had a history of infection, most frequently urethritis (68%). Forty-four percent had a history of mucocutaneous lesions. All patients demonstrated ocular involvement at the time of diagnosis (68% with unilateral and 32% with bilateral disease), 84% had evidence of uveitis, 3% had scleritis, 2% had conjunctivitis, and 1% had pars planitis and iridocyclitis. During follow-up, the ocular complications included conjunctivitis (96%), anterior uveitis (92%), posterior uveitis (64%), keratitis (64%), cataract (56%), intermediate uveitis (40%), scleritis (28%), cystoid macular edema (28%), papillitis (16%), and glaucoma (16%). Systemic treatment for ocular inflammation was initiated in all patients. Ninety-six percent were treated with nonsteroidal anti-inflammatory agents. Eighty-eight percent were treated with corticosteroids, 64% requiring systemic prednisone. Immunosuppressive therapy was initiated in 52% of patients, with all receiving methotrexate. Seven patients required more than one immunosuppressive agent. The mean initial visual acuity was 20/25 in the right eye and 20/30 in the left eye. The mean final visual acuity was 20/25 in the right eye and 20/25 in the left eye. CONCLUSIONS: Reiter's syndrome may be associated with chronic recurrent ocular inflammation. Systemic therapy (including immunosuppressive treatment) typically is required to control the ocular inflammation and to prevent progressive visual loss.

Intravenous immunoglobulin therapy in patients with ocular-cicatricial pemphigoid: a long-term follow-up.

OBJECTIVE: To report the clinical outcome and long-term follow-up of 10 patients with progressive ocular-cicatricial pemphigoid (OCP), nonresponsive to conventional therapy and treated with IV immunoglobulin (IVIg) therapy, reported earlier as a preliminary study. DESIGN: Noncomparative, prospective, interventional case series according to a defined protocol for IVIg therapy. PARTICIPANTS: Ten patients, with a diagnosis of OCP present bilaterally confirmed by both biopsy and immunofluorescence studies and who had failed conventional therapy and had objectively demonstrated a positive response to IVIg therapy in a preliminary study, published in 1999. MAIN OUTCOME MEASURES: Comparison of objective clinical outcome parameters before and after IVIg therapy, including visual acuity (VA) and prevention of progression of subepithelial conjunctival fibrosis and blindness. RESULTS: All 10 patients initially demonstrated signs of clinical improvement with IVIg therapy. The total number of IVIg cycles ranged from 20 to 42 (mean, 32), and the total duration of IVIg therapy ranged from 25 to 43 months (mean, 35). Eight patients who completed the protocol had an improvement in their VA and did not have further progression of subepithelial conjunctival fibrosis. These 8 patients have been maintained in a sustained remission for a total follow-up period ranging from 24 to 48 months (mean, 35) after the discontinuation of IVIg therapy. Two patients did not complete the protocol. Both had initially demonstrated a positive clinical response. One patient had worsening of the OCP and, after IVIg therapy, was abruptly and involuntarily withdrawn. In the second patient, deterioration occurred after ocular surgery. Intravenous immunoglobulin therapy was not provided postoperatively. These 2 patients who did not complete the protocol lost vision. CONCLUSIONS: Intravenous immunoglobulin therapy is an effective treatment in OCP in patients nonresponsive to conventional therapy. In 8 patients who completed the protocol, progression of the disease was not observed. A gradual withdrawal of IVIg therapy, as described in the protocol, may be beneficial in maintaining a sustained clinical remission. Abrupt cessation or discontinuation can result in a severe recurrence that may possibly progress to blindness.

Biology of interleukin-5 in ocular cicatricial pemphigoid.

BACKGROUND: Ocular cicatricial pemphigoid (OCP) is an autoimmune disease characterized by the presence of autoantibodies, T-cell dysregulation, and abnormal serum levels of cytokines such as interleukin-6, interleukin-1, and tumor necrosis factor-alpha. The purpose of the present study was to investigate levels of interleukin-5 (IL-5) in the sera, eosinophil counts in the peripheral blood, and eosinophil and mast cell counts in the inflamed conjunctivae of patients with active OCP. METHODS: Seven patients diagnosed in the active phase of OCP presenting with chronic cicatrizing conjunctivitis were studied. The serum levels of IL-5 were compared to a group of seven age-, race-, and sex-matched normal human subjects. Eosinophil and mast cell counts in the patients' conjunctivae were compared to those in normal conjunctivae harvested during cataract surgery from seven normal individuals. In addition, eosinophil counts in peripheral blood of patients with active OCP were compared to those in normal individuals. RESULTS: The mean serum level of IL-5 in patients with active OCP was higher (67.23 pg/ml, range 46.33-98.26 pg/ml) than that in normal individuals (12.18 pg/ml, range 7.66-18.86). The difference was statistically significant ( P<0.001). On light microscopy the biopsied conjunctivae stained with hematoxylin and eosin revealed statistically significant differences ( P<0.001) in the mean numbers of eosinophils in the substantia propria between the patients with active OCP (6.8 cells/cm(2), range 4.8-8.2 cells/cm(2)) and normal controls (0.91 cells/cm(2), range 0.4-1.8 cells/cm(2)). The average number of mast cells found in the substantia propria of the biopsied conjunctivae was statistically significantly higher in patients with OCP (13.79 cells/cm(2), range 6.6-19.4) than in normal individuals (4.34 cells/cm(2), range 3.2-7.8; P<0.01). The average number of eosinophils in the peripheral blood of patients with active OCP (6.6x10(7)/l, range 2.9 - 9.3x10(7)/l) was statistically significantly higher ( P<0.01) than in normal controls (2.09x10(7)/l, range 0 - 4.5x10(7)/l). CONCLUSIONS: The results suggest that IL-5 may play an important role in the pathogenesis of OCP.

A nonrandomized comparison of the clinical outcome of ocular involvement in patients with mucous membrane (cicatricial) pemphigoid between conventional immunosuppressive and intravenous immunoglobulin therapies.

The purpose of this study was to compare the clinical outcomes of intravenous immunoglobulin (IVIg) therapy to conventional immunosuppressive therapy in patients with mucous membrane pemphigoid (MMP), also known as cicatricial pemphigoid (CP), whose disease progressed to involve the eye. Before ocular involvement, all the patients in this study were diagnosed and treated with immunosuppressive agents, for biopsy-proven MMP, affecting the skin and/or mucous membranes, other than the conjunctiva. Eight patients in group A were treated with IVIg after the diagnosis of ocular cicatricial pemphigoid (OCP) was established. The efficacy and safety of IVIg therapy were compared to a clinically similar group of eight patients treated with conventional immunosuppressive therapy (group B). The inclusion criteria for both groups were: (1). presence of MMP at extraocular sites confirmed by biopsy before entry into the study; (2). entry into the study occurred when ocular involvement was noted and confirmed by biopsy; (3). presence of conventional immunosuppressive therapy at the time of ocular involvement; (4). a minimum of 18 months of follow-up after diagnosis of ocular involvement. The mean length of the therapy, after the onset of ocular involvement, was 24 months (range 16-30) in group A and 45 months (range 21-90) in group B. The median time between initiation of therapy and clinical remission in group A and group B was 4 and 8.5 months, respectively. This difference was statistically significant (P < 0.01). No recurrence of ocular inflammation was recorded in any of the patients in group A. On the contrary, at least one recurrence (median 1) was recorded in five patients in group B (range 0-4). This difference was statistically significant (P < 0.05). All eight patients in group A and group B presented to the ophthalmologist in stage 2 of OCP at the time of the initial visit. At the last follow-up visit, no progression to advanced stages of OCP was recorded in all eight patients in group A. On the contrary, only four patients in group B remained in stage 2 of OCP at the last follow-up exam. The conjunctival scaring progressed from stage 2 to stage 3 in the remaining four patients of group B. At the last follow-up visit, both eyes of each patient in group A were free of inflammation. Some level of conjunctival inflammation at the last follow-up visit was noted in five patients in group B (range 0-1.5, P < 0.05). Both groups of patients were studied during the same time period. The results of this study suggest that ocular involvement in patients with MMP may be considered an indication for initiating IVIg therapy, since it was more effective in arresting progression of OCP, when compared to conventional immunosuppressive therapy. These data indicate that IVIg produced a faster control of the acute inflammation and that no recurrences were observed during the follow-up. This clinical difference could be because of the reduced production of pathogenic antibody, and/or restoration of the immunoregulation, which may have been disturbed.