Jurkunas U, Behlau I, Colby K. Fungal keratitis: changing pathogens and risk factors. Cornea. 2009;28 (6) :638-43.Abstract
PURPOSE: To describe changes in demographics and pathogens for fungal keratitis cases diagnosed at the Massachusetts Eye and Ear Infirmary. METHODS: Patient demographics, clinical and laboratory findings, treatment and outcomes of 46 cases of culture-proven fungal keratitis diagnosed from January 2004 through November 2007 were compared with 23 cases of fungal keratitis previously collected over a similar period from January 1999 through November 2002. RESULTS: During 2004-2007, the rate of fungal keratitis was 1.0 cases per month, an increase from the baseline rate of 0.5 cases per month during 1999-2002. The proportion of cases caused by filamentous fungi increased from 30% (1999-2002) to 65% (2004-2007) (P = 0.01). Soft contact lens wear accounted for 41% of fungal keratitis cases in 2004-2007, as compared with 17% in 1999-2002. The majority of patients (70%) received oral antifungal treatment in addition to topical amphotericin B and natamycin. Seventeen patients (40%) required therapeutic keratoplasty. Patients with a history of corneal transplant had the highest rate of therapeutic keratoplasties (67%) and had the poorest visual outcome (40% counting fingers or less). In the contact lens group, 94% of patients maintained vision of at least 20/40 and only 12% required surgery to control the infection. CONCLUSIONS: There has been an increase in fungal keratitis in the Boston area and a change in the causative pathogens and risk factors for infection. Filamentous fungi now account for the majority of fungal keratitis cases, whereas yeasts were the predominant pathogen in the past. Soft contact lens wear is currently the most common risk factor for development of fungal keratitis.
Jurkunas UV, Rawe I, Bitar MS, Zhu C, Harris DL, Colby K, Joyce NC. Decreased expression of peroxiredoxins in Fuchs' endothelial dystrophy. Invest Ophthalmol Vis Sci. 2008;49 (7) :2956-63.Abstract
PURPOSE: To compare the relative expression of peroxiredoxin (Prx) proteins in normal human corneal endothelium with endothelium in corneas affected by Fuchs' endothelial dystrophy (FED) and between normal human endothelium and epithelial/stromal tissue. METHODS: Human corneal endothelial cell-Descemet's membrane (HCEC-DM) complexes from normal and FED corneal buttons were dissected from the epithelium/stroma. For proteomic analysis, HCEC-DM protein extracts were separated by using two-dimensional gel electrophoresis. Relative differences in protein spot density was analyzed. Proteins of interest, including Prx isoforms, were identified by MALDI-TOF (matrix-assisted desorption ionization-time of flight) mass spectrometry. Western blot analysis compared the relative expression of Prx isoforms in normal and FED endothelium and between normal endothelium and normal epithelium/stroma. Expression of Prx-2 mRNA was compared by using real-time PCR. RESULTS: Proteomic analysis identified differences in the relative expression of Prx isoforms between normal and FED endothelium. Western blot analysis confirmed that expression of Prx-2, -3, and -5 was significantly decreased (P < 0.05) in FED cells. Normal HCECs expressed significantly (P < 0.05) higher levels of Prx-2 and -3 than did the epithelium/stroma. Expression of Prx-5 was not significantly different (P > 0.05) in the endothelium versus the epithelium/stroma. Real-time PCR analysis revealed that Prx-2 mRNA was significantly decreased (P = 0.027) in FED samples. CONCLUSIONS: Prx proteins were identified in human corneal endothelium. The fact that Prx-2 and -3 were expressed at significantly higher levels in HCEC-DM compared with the epithelium/stroma reflects the different physiologic activities of individual corneal cell types. Significantly decreased expression of Prx-2, -3, and -5 in FED may suggest an alteration in the ability of endothelial cells to withstand oxidant-induced damage and may be closely related to the pathogenesis of this disease.
Jurkunas UV, Bitar MS, Rawe I, Harris DL, Colby K, Joyce NC. Increased clusterin expression in Fuchs' endothelial dystrophy. Invest Ophthalmol Vis Sci. 2008;49 (7) :2946-55.Abstract
PURPOSE: To investigate the differential expression of the glycoprotein clusterin/apoJ (CLU) in normal and Fuchs' endothelial dystrophy (FED) corneal endothelium and to compare the expression of various forms of CLU in normal and FED tissue. METHODS: FED and pseudophakic bullous keratopathy (PBK) corneal buttons were removed during transplantation, and normal corneas were obtained from tissue banks. Human corneal endothelial cells and Descemet's membrane (HCEC-DM) complex was dissected from the stroma. Proteins were separated on 2-D gels and subjected to comparative proteomic analysis. Relative expression of presecretory CLU (pre-sCLU), secretory (s)CLU, and nuclear (n)CLU were compared between normal and FED HCEC-DM by Western blot analysis. Expression of CLU mRNA was compared by using RT-PCR. Subcellular localization of CLU was compared in corneal wholemounts from normal eyes and eyes with FED by immunocytochemistry followed by confocal microscopy. RESULTS: Proteomic analysis revealed an apparent increase in CLU expression in FED HCEC-DM compared with the normal control. Western blot analysis demonstrated that pre-sCLU protein expression was 5.2 times higher in FED than in normal samples (P = 3.52E-05), whereas the mature form modified for secretion (sCLU) was not significantly elevated (P = 0.092). Expression of nCLU protein was significantly elevated in FED (P = 0.013). RT-PCR analysis revealed that CLU mRNA was significantly increased (P = 0.002) in FED samples, but not in PBK samples. CLU also had a distinctive localization in FED samples with enhanced intracellular staining around the guttae and in the nuclei of endothelial cells. CONCLUSIONS: CLU expression is markedly elevated in FED-affected tissue, pointing to a yet undiscovered form of dysregulation of endothelial cell function involved in FED pathogenesis.
Lee BW, Jurkunas UV, Harissi-Dagher M, Poothullil AM, Tobaigy FM, Azar DT. Ectatic disorders associated with a claw-shaped pattern on corneal topography. Am J Ophthalmol. 2007;144 (1) :154-156.Abstract
PURPOSE: To identify clinical findings associated with claw-shaped patterns on corneal topography. DESIGN: Retrospective, observational case series. METHODS: Forty eyes (26 patients) with classic claw-shaped patterns on corneal topography were identified from 3,993 Orbscan II records. They were subclassified into three groups: Group 1 (pellucid marginal degeneration [PMD] or PMD suspect); group 2 (keratoconus or keratoconus suspect); and group 3 (ectasia). The refractive and topographic indices of groups 1 and 2 were compared. RESULTS: There were nine eyes (six patients) in group 1, 27 eyes (18 patients) in group 2, and four eyes (two patients) in group 3. The mean radii of maximal anterior (2.96 mm) and posterior (3.06 mm) elevation in group 1 were significantly greater than those of group 2 (1.89 mm; P = .018 and 1.72 mm; P = .022, respectively). CONCLUSIONS: The claw-shaped pattern on corneal topography is not diagnostic of PMD; it is also seen in keratoconus.
Harissi-Dagher M, Dana RM, Jurkunas UV. Keratoglobus in association with posterior polymorphous dystrophy. Cornea. 2007;26 (10) :1288-91.Abstract
PURPOSE: To report a case of a 34-year-old woman presenting with keratoglobus and posterior polymorphous corneal dystrophy (PPMD). METHODS: Observational case report including ophthalmologic examination, topographic findings, and specular microscopy findings. RESULTS: This patient presented with corneal steepening on topography consistent with keratoglobus, as well as large areas of irregular polymorphous changes of the corneal endothelium on specular microscopy consistent with PPMD. CONCLUSIONS: We report the first case with clinical features of both keratoglobus and PPMD. This report brings forth the description of keratoglobus findings on Orbscan topography.
Jurkunas UV, Langston DP, Colby K. Use of voriconazole in the treatment of fungal keratitis. Int Ophthalmol Clin. 2007;47 (2) :47-59.
Yu EN, Jurkunas U, Rubin PAD, Baltatzis S, Foster SC. Obliterative microangiopathy presenting as chronic conjunctivitis in a patient with relapsing polychondritis. Cornea. 2006;25 (5) :621-2.Abstract
PURPOSE: To report histopathologic findings and treatment of obliterative microangiopathy in a patient with chronic conjunctivitis due to relapsing polychondritis (RP). METHODS: This interventional case report describes a 50-year-old woman with relapsing polychondritis was referred to the Ocular Immunology and Uveitis Service for bilateral tearing due to refractory chronic conjunctivitis. Ocular examination revealed the presence of bilateral follicular conjunctivitis. Conjunctival biopsy of the inferior palpebral conjunctiva was performed, and the histopathologic findings guided the therapeutic intervention. RESULTS: The pathology of the conjunctival biopsy included granulomatous obliterative microangiopathy with numerous eosinophils, plasma cells, lymphocytes, and epithelioid cells in the substantia propia. The chronic conjunctivitis resolved with systemic methotrexate therapy. CONCLUSIONS: Microangiopathy may cause chronic conjunctivitis in patients with RP and may be a harbinger of evolving nonocular problems as a consequence of incomplete control of this autoimmune disorder. Immunomodulatory therapy should be considered in such cases to prevent possible cardiovascular, renal, respiratory, and neurologic complications of vasculitis. Although methotrexate has been used in treatment of RP-related necrotizing scleritis with poor results, it can be sufficient for the conjunctivitis with microangiopathy associated with RP.
Jurkunas U, Azar DT. Potential complications of ocular surgery in patients with coexistent keratoconus and Fuchs' endothelial dystrophy. Ophthalmology. 2006;113 (12) :2187-97.Abstract
PURPOSE: To describe the potential complications of cataract and refractive surgery in patients with Fuchs' endothelial dystrophy (FED) and keratoconus. DESIGN: Retrospective case series. PARTICIPANTS: Eight patients with FED and keratoconus in a large university group practice. METHODS: We reviewed the clinical and topographic findings of 8 patients (15 eyes) with FED and keratoconus. Clinical examination, corneal topography, specular microscopy were done, and sequential central corneal thickness (CCT) was obtained. Follow-up ranged from 1 month to 6 years. MAIN OUTCOME MEASURES: Findings of keratoconus and FED in preoperative evaluation. RESULTS: Five patients had concomitant cataracts; 3 had refractive errors and sought surgical correction. Cataract surgery was performed on 3 of 5 patients (5 eyes). LASIK was performed on one eye of 3 patients. Of 5 eyes that underwent cataract extraction, 4 had blurry vision after surgery. The interval between the surgical procedure and onset of symptoms ranged from 1 month to 4 years. The causes of decreased vision after cataract surgery were corneal edema and/or corneal ectasia. The CCT readings ranged from 426 to 824 microm. One of 4 symptomatic eyes underwent penetrating keratoplasty. The CCTs of 3 patients (6 eyes) who presented with refractive error ranged from 507 to 565 microm. One eye had undergone an attempted LASIK procedure resulting in a lost cap. Corneal topography and specular microscopy showed the coexistence of keratoconus and FED, and the patients were advised against having LASIK surgery. CONCLUSIONS: Corneal thinning caused by keratoconus and concurrent increase in corneal thickness caused by FED may combine to normalize the corneal pachymetry readings; disease severity may be underestimated, which may lead to unexpected postoperative visual outcomes. Routine use of preoperative topography and specular microscopy may help to avert potential surgical complications.