Adam H. Kaufman

Rituximab for refractory granulomatous eye disease.

Objective To determine the effectiveness of rituximab therapy for patients with granulomatous disease of the eye. Methods Retrospective review was undertaken of cases seen at a single institution for ocular antineutrophil cytoplasmic antibody-associated vasculitis or sarcoidosis with persistent ocular disease despite systemic therapy. All patients were treated with rituximab and followed for at least 6 months. Results Nine patients were identified (five with antineutrophil cytoplasmic antibody-associated vasculitis, four with sarcoidosis), and all were treated for at least 6 months. Eight experienced improvement of eye disease and were able to reduce prednisone and other drug therapies. One patient remained stable, but still required high dosages of prednisone. All five patients with lung disease improved with rituximab therapy. Rituximab treatment was well tolerated. Two patients discontinued the drug due to leukopenia; however, both patients reinstituted rituximab at modified doses. Conclusion Rituximab therapy was effective in controlling granulomatous ocular disease in most cases. The drug was corticosteroid-sparing and effective in refractory cases, with no severe adverse events encountered.

Expression of collagens I, III, IV and V mRNA in excimer wounded rat cornea: analysis by semi-quantitative PCR.

A semi-quantitative polymerase chain reaction (PCR) methodology was used to evaluate the kinetic changes occurring in collagens I, III, IV and V mRNA in rat cornea following excimer laser keratectomy. cDNA was synthesized from RNA extracted from rat cornea at various times following excimer laser photoablative keratectomy. Collagen cDNA sequences were subsequently amplified using specific sets of oligonucleotide primers. Competitive PCR amplification was carried out using an internal standard so that a semi-quantitative analysis of message for synthesis of collagen types I, III, IV and V could be performed and time course dynamics of message for these collagens studied. There was a biphasic increase in the levels of collagens III, IV and V mRNA following excimer laser keratectomy. Collagen I mRNA levels demonstrated a more sustained increase and were still elevated at 6 weeks following wounding. Collagens IV and V mRNA showed the largest increase with an approximate three fold increase over controls between 4 days and 1 week. Our results demonstrate that upregulation of stromal collagens I, III, and V mRNA and basement membrane collagen IV mRNA occurs in rat cornea following excimer laser keratectomy.

HLA typing in patients with ocular manifestations of Stevens-Johnson syndrome.

BACKGROUND Stevens-Johnson syndrome (SJS) is an acute, self-limited, inflammatory disorder of the skin and mucous membranes. With ocular involvement, SJS has been associated with the class I human leukocyte antigen (HLA)-Bw44. This study examined HLA class II associations in patients with SJS with ocular involvement to help identify possible molecular genetic mechanisms underlying disease susceptibility/resistance. METHODS Twenty-three white patients with ocular complications secondary to SJS had HLA class II typing performed using polymerase chain reaction-based molecular techniques. Genotype frequency was compared with results obtained from 175 control subjects. RESULTS HLA-DQB1*0601 was present in four (17%) patients with SJS and in five (3%) control subjects (P < 0.05; relative risk = 7.2). There was no association with HLA-DQB1*0301, which previously has been been strongly associated with recurrent erythema multiforme. None of the class II antigens tested appeared to offer a protective effect against the development of disease. CONCLUSION HLA-DQB1*0601 was found in a significantly disproportionate number of white patients with SJS and ocular complications. The presence of this allele may confer an increased risk for the development of SJS with ocular complications and provides further evidence for an underlying immunogenetic susceptibility to the development of this disease.

Successful surgical rehabilitation of children with traumatic corneal laceration and cataract.

OBJECTIVE To evaluate the visual and refractive outcome of corneal transplant surgery, cataract extraction, and intraocular lens (IOL) implantation in children with traumatic corneal laceration and cataract. DESIGN Retrospective, noncomparative case series. PARTICIPANTS Five patients, 7 years of age or younger, who underwent penetrating keratoplasty, cataract extraction, and IOL implantation for traumatic corneal laceration and cataract were identified. MAIN OUTCOME MEASURES Each case was analyzed retrospectively for the following factors: preoperative findings; surgical technique, including management of the posterior capsule; measurement of axial length and keratometry; calculation of IOL power, style, and type of IOL implanted; graft clarity; final visual acuity; and final refraction. RESULTS The five children ranged from 3 to 7 years of age at the time of trauma. All had primary repair of their injury before referral. Each patient was observed for more than 2 years. Each had a posterior chamber IOL placed in the sulcus. After surgery, no severe complications were observed. The preoperative visual acuity ranged from 20/400 to light perception. After surgery, all five patients had clear grafts and an improved visual acuity ranging from 20/20 to 20/400. The final spherical refraction in each patient was within 3.75 diopters (D) of plano, with 1.50 to 3.25 D of cylinder. CONCLUSIONS Successful surgical rehabilitation was accomplished in these patients. Despite their young age and the difficulty in determining IOL power, combining surgery and aggressive amblyopia therapy resulted in visual rehabilitation with refractions approaching emmetropia.

Expression of fibronectin isoforms bearing the alternatively spliced EIIIA, EIIIB, and V segments in corneal alkali burn and keratectomy wound models in the rat.

Purpose: To better understand the healing process in the wounded cornea, fibronectin (FN) isoforms bearing the alternatively spliced EIIIA, EIIIB, and V segments (EIIIA+, EIIIB+, and V+ FNs) were evaluated in alkali burn and keratectomy wound models in the rat. Methods: Alkali burn or keratectomy wounds (both 2 mm) were created, and corneas were harvested at various time points and analyzed by indirect immunofluorescence using antibodies specific for the EIIIA, EIIIB, and V segments as well as for the total pool of FN (total FN). Results: There was minimal staining for any variety of FN in the epithelium or basement membrane zone (BMZ) in normal cornea, but each antibody produced granular staining in the stroma. Bright staining for V+ and total FNs was evident at the denuded stromal surface 1 day following keratectomy. In contrast, staining for EIIIA+ and EIIIB+ FNs was negligible at 24 hours but appeared on the wound surface under the migrating unstained epithelium by the second day. BMZ staining for FN then gradually subsided, such that there was little or no staining by 6 weeks. In contrast, alkali burn wounds exhibited very little BMZ staining throughout the time course. Although there was preferential staining of the anterior aspect of Descemet membrane by anti-EIIIA and anti-EIIIB antibodies under normal conditions, the staining intensity of the anterior and posterior aspects became similar following corneal wounding. Conclusion: Deposition of EIIIA+ and EIIIB+ FNs in the BMZ of the keratectomy wound occurs more slowly than deposition of V+ and total FNs. EIIIA+ FN is expressed in a distribution that overlaps with that previously described for the α9 integrin subunit following corneal debridement, suggesting that EIIIA–α9 interactions could occur during corneal wound healing. In contrast, the relative lack of FN deposition in alkali burn wounds suggests that proteolytic degradation of FN may occur; and this, along with impairment of new FN synthesis because of cellular damage, could play a role in the high prevalence of recurrent epithelial erosions in alkali-wounded corneas.

Pediatric airbag-associated ocular trauma and endothelial cell loss.

BACKGROUND Airbag-associated ocular trauma among the adult population has been widely reported, but reports of these injuries in children are sparse. Laboratory experiments suggest that airbag-associated ocular trauma may cause endothelial cell loss, but reports of in vivo human endothelial cell counts are anecdotal. METHODS A retrospective chart review was performed of all patients with airbag-associated ocular trauma at a pediatric hospital from 1995 to 2001. From 2001 to 2002, endothelial cell counts were obtained from 9 eyes of airbag-associated ocular trauma subjects and 22 eyes of control subjects. RESULTS Sixteen patients were identified; all had periocular abrasions, edema, and/or ecchymosis. Other ocular injuries included corneal abrasions (n = 9 or 56%), corneal edema (n = 8 or 50%), hyphema (n = 7 or 44%), lens opacities (n = 5 or 31%), and macular scars (n = 2 or 12%). Three eyes of three patients required intraocular surgery. Unilateral visual loss (hand-motions, 20/100) occurred in two patients. A decrease in mean endothelial cell count of 547 cell/mm2 (P =.01) was found in the airbag-associated ocular trauma group eyes when compared with control group eyes. CONCLUSIONS The present study includes the largest reported case series of pediatric airbag-associated ocular trauma. Airbag-associated ocular trauma may necessitate intraocular surgery, may result in permanent visual loss, and may cause endothelial cell loss in pediatric patients.

Etanercept for Refractory Ocular Sarcoidosis

PURPOSES Study a tumor necrosis factor receptor antagonist (etanercept) in the treatment of chronic ocular sarcoidosis. SUBJECTS AND METHODS Eighteen patients with ocular sarcoidosis and ongoing inflammation in the eyes. All patients had received at least 6 months of therapy with methotrexate and were currently receiving corticosteroids. Patients were randomized to receive either etanercept, 25 mg subcutaneously twice a week, or placebo in a double-blind randomized trial. Treatment for ocular inflammation with systemic and local corticosteroids at the beginning and end of 6 months of treatment was noted. All patients underwent an ocular examination at the beginning and the end of the study by one ophthalmologist who was unaware of what treatment the patient was receiving. RESULTS Three of the patients treated with etanercept and one treated with placebo were being treated with lower doses of corticosteroids by the end of the study. However, three of the etanercept patients and one of the placebo patients required larger doses of corticosteroids by the end of the study. The ophthalmology global assessment improved for two of the etanercept-treated patients and three of the placebo-treated patients. CONCLUSION For most patients, therapy with etanercept was not associated with a significant improvement in their chronic ocular disease.

Pediatric Herpes Virus Anterior Segment Infections

This chapter is designed as a practical guide for diagnosis and management of anterior segment herpetic disease in children. When these potentially serious infections occur in childhood, the pediatric ophthalmologist frequently coordinates the acute and long-term management. In atypical or severe cases, consultation with a cornea, uveitis, or infectious disease specialist may be necessary. Although complex diagnostic and treatment descriptions are possible, this chapter provides generalized guidance through defined categories of disease with delineated treatment protocols. Herpes simplex virus (HSV) is the primary focus of the chapter, and the text emphasizes pediatric blepharoconjunctivitis, epithelial keratitis, stromal keratitis, endotheliitis, iritis, and neonatal disease. Varicella zoster virus (VZV) infections are also briefly discussed. Treatment flow diagrams and clinical photographs are presented for additional guidance.