The role of conjunctival biopsy in the diagnosis of granulomatosis with polyangiitis.

BACKGROUND: The purpose of this study is to describe a patient who was diagnosed with granulomatosis with polyangiitis based on conjunctival biopsy. This study is a case report and review of the literature. FINDINGS: A 48-year-old Caucasian woman presented with a 2-week history of a left eye peripheral corneal ulcer with adjacent conjunctivitis and a 4-month history of a non-resolving productive cough. Given her elevated serum perinuclear antineutrophil cytoplasmic antibody (P-ANCA) and erythrocyte sedimentation rate (ESR) levels as well as a chest computed topography (CT) that showed bilateral patchy infiltrates, suspicion of limited granulomatosis with polyangiitis with lung and ocular involvement was high. Because bronchoalveolar lavage was nondiagnostic for granulomatous disease, conjunctival biopsy was initially attempted in order to avoid a more invasive lung biopsy. The conjunctival biopsy revealed mixed subacute inflammatory mediators and vasculitis consistent with granulomatosis with polyangiitis. CONCLUSIONS: Conjunctival biopsy may be a valuable, minimally invasive method for diagnosing systemic granulomatosis with polyangiitis.

Comparison of artemis 2 ultrasound and Visante optical coherence tomography corneal thickness profiles.

PURPOSE: To compare corneal thickness profiles of cross-sections of cornea determined by arc-scanned immersion ultrasound and optical coherence tomography (OCT). METHODS: Corneas of 28 eyes from 14 participants were scanned in triplicate using the Artemis 2 high-frequency arc-scanned ultrasound system (ArcScan Inc) and the Visante OCT system (Carl Zeiss Meditec). Corneal thickness and reproducibility were compared within 3.5 mm of central cornea in the horizontal plane. RESULTS: Although highly correlated, Visante central and peripheral corneal thickness values were systematically thinner than Artemis 2 values. Within the central 0.5 mm, the difference was approximately 8 µm, but the difference increased with distance from the center. Reproducibility for each instrument was comparable, measuring <4 µm centrally and increasing peripherally. CONCLUSIONS: Visante OCT measurements of corneal thickness are thinner than Artemis 2 ultrasound values centrally with an increasing difference with peripheral position. Measurement reproducibility was comparable for the two techniques.

Hypocellular scar formation or aberrant fibrosis induced by an intrastromal corneal ring: a case report.

INTRODUCTION: Intrastromal corneal rings or segments are approved for the treatment of myopia and astigmatism associated with keratoconus. We describe a clinicopathological case of intrastromal corneal rings. For the first time, the molecular pathological findings of intrastromal corneal rings in the cornea are illustrated. CASE PRESENTATION: A 47-year-old African-American man with a history of keratoconus and failure in using a Rigid Gas Permeable contact lens received an intrastromal corneal ring implant in his left eye. Due to complications, penetrating keratoplasty was performed. The intrastromal corneal ring channels were surrounded by a dense acellular (channel haze) and/or hypocellular (acidophilic densification) collagen scar and slightly edematous keratocytes. Mild macrophage infiltration was found near the inner aspect of the intrastromal corneal rings. Molecular analyses of the microdissected cells surrounding the intrastromal corneal ring channels and central corneal stroma revealed 10 times lower relative expression of IP-10/CXCL10 mRNA and two times higher CCL5 mRNA in the cells surrounding the intrastromal corneal ring, as compared to the central corneal stroma. IP-10/CXCL10 is a fibrotic and angiostatic chemokine produced by macrophages, endothelial cells and fibroblasts. CONCLUSION: An intrastromal corneal ring implant can induce hypocellular scar formation and mild inflammation, which may result from aberrant release of fibrosis-related chemokines.

Pain perception in sequential cataract surgery: comparison of first and second procedures.

PURPOSE: To compare pain and anxiety between first and second cataract extractions under topical anesthesia with monitored anesthesia care. SETTING: University ophthalmology clinic. DESIGN: Cohort study. METHODS: Consecutive adults having bilateral sequential clear corneal cataract extraction using phacoemulsification under topical anesthesia with monitored anesthesia care were recruited. Exclusion criteria included baseline eye pain, poor comprehension, and complicated cataract extraction. Patients completed 4 short perioperative surveys with each cataract extraction as follows: the Amsterdam Preoperative Anxiety and Information Scale (APAIS) and the State-Trait Anxiety Scale (STAI) preoperatively and a 0-to-10 visual analog scale pain survey twice after surgery. Pain and difference in pain were the primary outcomes. RESULTS: Of the 65 patients who completed the study, 26 (40%) reported higher visual analog scale pain scores for the second cataract extraction. Overall, the median pain score was 0 (range 0 to 6) for the first cataract extraction and 1 (range 0 to 9) for the second (P = .004). By 1 day postoperatively, the pain scores were similar (median 0; range 0 to 9; P = .58). Both APAIS and STAI anxiety scores decreased between surgeries (P = .003 and P < .001, respectively). CONCLUSIONS: Although cataract extraction remained relatively painless under topical anesthesia with monitored anesthesia care, there was a subtle increase in pain in the second surgery relative to the first. This appears to be associated with decreased preoperative anxiety and may be related to the amnestic effects of intravenous sedation. These data may explain a common operative observation. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Role of human herpes virus 6 in corneal inflammation alone or with human herpesviruses.

PURPOSE: : The purpose of this study was to determine the association of human herpes virus 6 (HHV-6) and/or other human herpesviruses in corneal inflammation using polymerase chain reaction (PCR). METHODS: : We collected tear films, conjunctival smears, and a corneal button of inflamed cornea, and the presence of HHV-6 and other herpesviruses in these samples were assessed by a nested PCR. RESULTS: : In tear films collected from 3 of 9 patients with dendritic keratitis, HHV-6 DNA was positive twice, together with herpes simplex virus (HSV) or varicella zoster virus DNA most often, during the acute phase of the disease. Two other patients in this group were either positive for HSV-1 and varicella zoster virus or for HSV-1 and Epstein-Barr virus DNA but negative for HHV-6. When another 12 patients' smear samples from corneal ulcer or keratouveitis were examined, 9 were positive for HHV-6 DNA. Of these, 4 were positive for HSV-1 simultaneously, whereas the remaining 5 patients were negative for HSV-1. One patient's smear was positive for HSV-1 but not for HHV-6. In the corneal button, both HSV and HHV-6 DNAs were positive by nested PCR. HHV-6 was also positive by nested PCR in the conjunctival swab obtained from the contralateral inflamed eye of the patient. CONCLUSIONS: : In 22 patients with corneal inflammation, HHV-6 was positive in 14 of 22 patients and HSV-1 was found in 9 of those patients. These data indicated that the association of HHV-6 with disease was more frequent than with other herpesviruses and that HHV-6 may be another sole causative agent for corneal inflammation.

Anterior-segment imaging for assessment of glaucoma.

This article summarizes the physics, technology and clinical application of ultrasound biomicroscopy (UBM) and optical coherence tomography (OCT) for assessment of the anterior segment in glaucoma. UBM systems use frequencies ranging from approximately 35 to 80 MHz, as compared with typical 10-MHz systems used for general-purpose ophthalmic imaging. OCT systems use low-coherence, near-infrared light to provide detailed images of anterior segment structures at resolutions exceeding that of UBM. Both technologies allow visualization of the iridocorneal angle and, thus, can contribute to the diagnosis and management of glaucoma. OCT systems are advantageous, being noncontact proceedures and providing finer resolution than UBM, but UBM systems are superior for the visualization of retroiridal structures, including the ciliary body, posterior chamber and zonules, which can provide crucial diagnostic information for the assessment of glaucoma.

Traumatic flap striae 6 years after LASIK: case report and literature review.

PURPOSE: To report a case of traumatic flap striae without flap dislocation 6 years after LASIK and provide a literature review of surgical flap striae, late traumatic flap striae, and their management. METHODS: A 28-year-old man presented with late traumatic flap striae without concurrent flap dislocation, which closely approximated the longest reported interval between LASIK and the development of flap striae. RESULTS: In the absence of flap dislocation, the finding of striae alone was subtle and went undetected initially. The flap was successfully refloated, stretched, and smoothed with recovery of 20/20 vision. CONCLUSIONS: Traumatic LASIK flap complications may occur many years after the original procedure. This report presents the first case of late traumatic flap striae without concurrent flap dislocation. Proper management can restore good visual function.

The effect of cyclosporine A (Restasis) on recovery of visual acuity following LASIK.

PURPOSE: To compare the recovery of uncorrected visual acuity (UCVA) following LASIK in patients treated with topical cyclosporine A 0.05% and patients treated with a standard postoperative regimen. METHODS: In this single-center, open-label, retrospective study, a standard refractive workup was performed in 45 patients (85 eyes) who underwent LASIK and did not have preexisting dry eye. In 36 eyes, a standard postoperative eye drop regimen was followed, and in 49 eyes, cyclosporine A 0.05% was added to the standard regimen for 12 weeks. Uncorrected visual acuity was measured 1 week and 1 and 3 months postoperatively. RESULTS: One week postoperatively, 22 (44.9%) eyes in the cyclosporine A group and 8 (22.2%) eyes in the standard treatment group had UCVA of 20/15. Cumulatively, 36 (73.5%) eyes in the cyclosporine A group and 24 (66.7%) eyes in the standard treatment group had UCVA of 20/20 or better. One month postoperatively, 37 (75.5%) in the cyclosporine A group and 23 (63.9%) eyes in the standard treatment group had UCVA of 20/20 or better. Three months postoperatively, 40 (81.6%) eyes in the cyclosporine A group and 25 (69.4%) eyes in the standard treatment group had UCVA of 20/20 or better. Mean UCVA in the cyclosporine A group showed statistically significant improvements compared with the standard treatment group. CONCLUSIONS: Cyclosporine A 0.05%, in the form of Restasis, may be an effective treatment for reducing the time needed for visual recovery after LASIK. Use of cyclosporine A was associated with overall better and faster recovery of UCVA.

A double-masked, randomized study to investigate the safety and efficacy of daclizumab to treat the ocular complications related to Behçet's disease.

PURPOSE: To investigate the safety and efficacy of daclizumab (Zenapax, humanized anti-Tac, HAT) in controlling the ocular manifestations of Behçet's disease. DESIGN: Randomized, placebo-controlled, double-masked clinical trial. PARTICIPANTS: Seventeen participants with Behçet's disease experiencing at least two prior ocular attacks and requiring treatment with immunosuppressive agents for the ocular complications of Behçet's disease. METHODS: Participants received either intravenous placebo or daclizumab (1 mg/kg) infusions every two weeks for six weeks, then every four weeks while continuing their standard immunosuppressive regimens. If clinically indicated, tapering of the standard immunosuppressive medications was allowed after six months of study enrollment. Complete ocular and physical examinations and an adverse event assessment were performed at baseline and prior to each study infusion. MAIN OUTCOME MEASURES: Primary safety endpoints were the development of a life-threatening complication or a severe opportunistic infection. Primary efficacy outcomes were the number of ocular attacks and an assessment of systemic immunosuppressive medications required during the study, including the ability to taper concomitant immunosuppressive therapy. RESULTS: Nine participants randomized to daclizumab and eight to placebo were followed monthly. Follow-up ranged from one to 34 months, with a median follow-up of 15 months. Two participants randomized to daclizumab discontinued study therapy prior to the end of the study for personal reasons. No participant experienced a safety endpoint, and visual acuity remained stable in all participants during the course of the study. Ten participants (six daclizumab, four placebo) experienced ocular attacks requiring therapy. The median ocular attack rate during the study was greater in the daclizumab arm than the placebo arm (median 1.27 vs. 0.17 attacks/year, respectively). Participants in the placebo arm also experienced a greater reduction in the immunosuppressive medication score compared to participants receiving daclizumab (median -4.0 vs. -1.0, respectively). CONCLUSIONS: The observed results in the placebo group demonstrate that careful follow-up and treatment with standard combination immunosuppressive therapy can be effective for the management of the ocular complications of Behçet's disease. In our small study, there was no suggestion that daclizumab was beneficial in comparison with placebo. However, the low observed attack rate limited our ability to make a definitive treatment group comparison.

Gamma interferon assay as an alternative to PPD skin testing in selected patients with granulomatous intraocular inflammatory disease.

BACKGROUND: To evaluate the QuantiFERON-TB test (gamma interferon assay), approved by the Centers for Disease Control and Prevention for the detection of latent tuberculosis (LTB), in patients who potentially may require immunosuppressive therapy for ocular inflammatory disease. METHODS: Blood samples from 12 consecutive patients with granulomatous ocular inflammatory disease were evaluated first with the purified protein derivative (PPD) skin test and then with the QuantiFERON-TB test (11 of 12 patients, 1 declined). The results of the 2 tests in both U.S.- and non-U.S.-born patients were compared with their Bacillus Calmette-Guérin (BCG) vaccination status and chest x-rays. RESULTS: In our small series there was a high degree of concordance between the QuantiFERON-TB assay and the PPD skin test. INTERPRETATION: The QuantiFERON-TB test did not demonstrate intrinsic merit over PPD skin testing for screening for LTB in selected patients when immunosuppressive therapy is considered. The confounding effect of BCG vaccination renders interpretation of both tests difficult. Early reports suggest the second-generation tests that are now available may hold promise for use in the uveitis clinic and should be formally evaluated.

Suppression of immune-mediated ocular inflammation in mice by interleukin 1 receptor antagonist administration.

OBJECTIVE: To evaluate the effects of an interleukin 1 receptor antagonist (IL-1RA) on the development of immune-mediated ocular inflammation in mice. METHODS: Recombinant, human, nonglycosylated IL-1RA (anakinra [kineret]) was tested for its inhibitory effects in 2 systems: (1) experimental autoimmune uveitis induced by interphotoreceptor retinoid-binding protein in B10.A mice using routine procedures and evaluated by clinical and histological examination, and (2) ocular inflammation in mice induced by transfer of hen egg lysozyme-specific T cells to hen egg lysozyme-transgenic mice. Treatment with IL-1RA included daily subcutaneous injections of the drug, at 300 and 500 mg/kg, or phosphate-buffered saline as control. RESULTS: Mean +/- SE experimental autoimmune uveitis scores of histological ocular changes of the mice at day 14 postimmunization with interphotoreceptor retinoid-binding protein were 1.5 +/- 0.3 in control mice; 1.0 +/- 0.4 in 300-mg/kg anakinra-treated mice; and 0.5 +/- 0.2 in 500- mg/kg anakinra-treated mice (P = .004). There was a corresponding decrease in the cellular immune response and cytokine production of immune cells in treated mice. Suppression of ocular inflammation by anakinra in the transfer system was also observed (P = .04). CONCLUSION: Human IL-1RA suppresses immune-mediated ocular inflammation in mice, affecting both the afferent and efferent components of the pathogenic immune response.Clinical Relevance Systemic administration of IL-1RA may have clinical application in the management of patients with uveitis.

Bilateral uveitis in a patient with autoimmune lymphoproliferative syndrome.

PURPOSE: We report a case of autoimmune lymphoproliferative syndrome (ALPS) presenting with bilateral uveitis. DESIGN: Observational case report. METHODS: Review of case record, serum and aqueous IL-10 and IL-6 cytokine results, and immunosuppressive treatment of a patient with a mutation in the gene encoding Fas. RESULTS: Control of the intermediate uveitis required sustained doses of topical and periocular corticosteroids as well as systemic cyclosporine. The serum IL-10 level was elevated, as commonly seen in ALPS, but the aqueous IL-10 was not. CONCLUSIONS: Despite a Th2 immune predominance in ALPS, uveitis, a Th1-mediated disease, may still manifest in these patients. The pathogenesis of uveitis in ALPS may differ from that of the systemic disease overall. Long-term follow-up is required for patients with uveitis associated with ALPS.

Humanized anti-interleukin-2 (IL-2) receptor alpha therapy: long-term results in uveitis patients and preliminary safety and activity data for establishing parameters for subcutaneous administration.

Therapy for severe uveitis is frequently long-term immunosuppression using systemic corticosteroids and cytotoxic agents, but side effects make long-term therapy difficult. A long-term (>4 year) Phase I/II single armed interventional study using intravenous anti-IL-2 receptor alpha treatments (daclizumab) and a short-term Phase II study evaluating the use of a subcutaneous daclizumab formulation were conducted. Patients were tapered off their systemic immunosuppressive therapy and received daclizumab infusions or subcutaneous injections at intervals varying from 2 to 6 weeks. In the long-term study, seven of ten enrolled patients were tapered from their original immunosuppressive medications and maintained exclusively on repeated daclizumab infusions for control of their uveitis for over 4 years. No patient was permanently removed from therapy for an adverse event ascribed to the medication. The use of 6-week infusion intervals led to recurrence of uveitis, while 2- to 4-week intervals did not. Only one patient developed measurable anti-daclizumab antibodies but this disappeared when subcutaneous therapy was begun. In the short-term study, four of the five patients receiving the subcutaneous formulation met the study endpoints for success within the first 12 weeks. All five were successful by 26 weeks. These studies provide preliminary evidence that regularly administered long-term daclizumab therapy can be given in lieu of standard immunosuppression for years to treat severe uveitis and that subcutaneously administered daclizumab appeared to be a clinically viable treatment strategy. These studies suggest that anti-IL-2 receptor blockade could be useful in the treatment of Th1-mediated autoimmune conditions.

Ultrasound measurement of the effect of temperature on microperfusion in the eye.

Recent developments in ultrasound (US) technology have allowed the study of microperfusion in the anterior segment of the eye. Our aim was to determine the effect of the thermal environment on blood flow in the anterior segment. We measured blood flow in the major arterial circle of five rabbits. A 38-MHz US transducer was coupled to the eye with a normal saline water-bath with temperature controlled from 1 degrees C to 38 degrees C. The major arterial circle was localized and imaged using the swept-scan technique and M-mode data were then acquired for measurement of pulsatile flow. Peak systolic and mean velocity averaged 4.51 and 1.32 mm/s, respectively. Positive correlations were found between peak systolic (1.69%/ degrees C) and mean (1.76%/ degrees C) velocities and temperature. Vessel diameter (mean = 178 microm) did not show any significant change with temperature. High-resolution US flowmetry demonstrated decreasing flow rates in the iris with decreasing temperature.