John A. Irvine

Clinical and microbiological characteristics of fungal keratitis in the United States, 2001-2007: a multicenter study.

OBJECTIVE To study the epidemiology, clinical observations, and microbiologic characteristics of fungal keratitis at tertiary eye care centers in the United States. DESIGN Retrospective multicenter case series. PARTICIPANTS Fungal keratitis cases presenting to participating tertiary eye care centers. METHODS Charts were reviewed for all fungal keratitis cases confirmed by culture, histology, or confocal microscopy between January 1, 2001, and December 31, 2007, at 11 tertiary clinical sites in the United States. MAIN OUTCOME MEASURES Frequency of potential predisposing factors and associations between these factors and fungal species. RESULTS A total of 733 cases of fungal keratitis were identified. Most cases were confirmed by culture from corneal scraping (n = 693) or biopsies (n = 19); 16 cases were diagnosed by microscopic examination of corneal scraping alone; and 5 cases were diagnosed by confocal microscopy alone. Some 268 of 733 cases (37%) were associated with refractive contact lens wear, 180 of 733 cases (25%) were associated with ocular trauma, and 209 of 733 cases (29%) were associated with ocular surface disease. No predisposing factor was identified in 76 cases (10%). Filamentous fungi were identified in 141 of 180 ocular trauma cases (78%) and in 231 of 268 refractive contact lens-associated cases (86%). Yeast was the causative organism in 111 of 209 cases (53%) associated with ocular surface disease. Yeast accounted for few cases of fungal keratitis associated with refractive contact-lens wear (20 cases), therapeutic contact-lens wear (11 cases), or ocular trauma (21 cases). Surgical intervention was undertaken in 26% of cases and was most frequently performed for fungal keratitis associated with ocular surface disease (44%). Surgical intervention was more likely in cases associated with filamentous fungi (P = 0.03). Among contact lens wearers, delay in diagnosis of 2 or more weeks increased the likelihood of surgery (age-adjusted odds ratio = 2.2; 95% confidence interval, 1.2-4.2). CONCLUSIONS Trauma, contact lens wear, and ocular surface disease predispose patients to developing fungal keratitis. Filamentous fungi are most frequently the causative organism for fungal keratitis associated with trauma or contact lens wear, whereas yeast is most frequently the causative organism in patients with ocular surface disease. Delay in diagnosis increases the likelihood of surgical intervention for contact lens-associated fungal keratitis.

Trends in Fungal Keratitis in the United States, 2001 to 2007

OBJECTIVE Fungal keratitis is a serious ocular infection that is considered to be rare among contact lens wearers. The recent Fusarium keratitis outbreak raised questions regarding the background rate of Fusarium-related keratitis and other fungal keratitis in this population. DESIGN Retrospective, multicenter case series. PARTICIPANTS Six hundred ninety-five cases of fungal keratitis cases who presented to 1 of 10 tertiary medical centers from 2001 to 2007. METHODS Ten tertiary care centers in the United States performed a retrospective review of culture-positive fungal keratitis cases at their centers between January 2001 and December 2007. Cases were identified using microbiology, pathology, and/or confocal microscopy records. Information was collected on contact lens status, method of diagnosis, and organism(s) identified. The quarterly number of cases by contact lens status was calculated and Poisson regression was used to evaluate presence of trends. The Johns Hopkins Medicine Institutional Review Board (IRB) and the IRBs at each participating center approved the research. MAIN OUTCOME MEASURES Quarterly number of fungal keratitis cases and fungal species. RESULTS We identified 695 fungal keratitis cases; 283 involved the use of contact lenses. The quarterly number of Fusarium cases increased among contact lens wearers (CLWs) during the period that ReNu with MoistureLoc (Bausch & Lomb, Rochester, NY) was on the market, but returned to prior levels after withdrawal of the product from the market. The quarterly frequency of other filamentous fungi cases showed a statistically significant increase among CLWs comparing October 2004 through June 2006 with July 2006 through December 2007 with January 2001 through September 2004 (P < 0.0001). CONCLUSIONS The quarterly number of Fusarium fungal keratitis cases among CLWs returned to pre-Renu with Moistureloc levels after removal of the product from the market. However, the number of other filamentous fungal keratitis cases, although small, seems to have increased among refractive CLWs. Reasons for these apparent increases are unclear.

Fungal keratitis caused by Scedosporium apiospermum: report of two cases and review of treatment.

Purpose. We report our experience in treating two cases of Scedosporium apiospermum keratitis and provide a review of basic scientific and clinical data regarding the treatment of this visually devastating disease. Method. We present a case report and literature review. Results. A 35-year-old woman and a 73-year-old man both reported pain, redness, and a foreign body sensation in the eye after trauma. They were initially treated with antibacterials. When cultures were positive for S. apiospermum, the first patient was treated with fluconazole and amphotericin with good results. The second was treated with fluconazole and natamycin, but the infection persisted and the eye was eventually enucleated. Review of the literature showed variable responsiveness of S. apiospermum to antifungal treatment. Conclusions. It is difficult to predict how S. apiospermum keratitis will respond to treatment, but miconazole appears to be useful in conjunction with other antifungals. Voriconazole shows promise as an effective alternative.

Tear cathepsin S as a candidate biomarker for Sjögren's syndrome.

The diagnosis of Sjögrens syndrome (SS) in routine practice is largely a clinical one and requires a high index of suspicion by the treating physician. This great dependence on clinical judgment frequently leads to delayed diagnosis or misdiagnosis. Tear protein profiles have been proposed as simple and reliable biomarkers for the diagnosis of SS. Given that cathepsin S activity is increased in the lacrimal glands and tears of NOD mice (a murine model of SS), the aim of this study was to explore the clinical utility of using tear cathepsin S (CTSS) activity as a biomarker for SS.

Functional and visual improvement with prosthetic replacement of the ocular surface ecosystem scleral lenses for irregular corneas.

Purpose: To evaluate the Doheny Eye Institute Experience with Prosthetic Replacement of the Ocular Surface Ecosystem (PROSE) scleral lenses for the management of irregular corneas with outcomes based on visual acuity (VA) and visual function. Methods: A retrospective chart review of 58 subjects (90 eyes) with irregular corneal surfaces referred to the Doheny Eye Institute for PROSE treatment between July 2009 and December 2011 was performed. The best-corrected VA before and after PROSE fitting was recorded. A functional assessment before and after PROSE fitting was also performed using the Ocular Surface Disease Index, a 12-item questionnaire that grades the severity of ocular discomfort and vision-related function. Results: Keratoconus (43%) represented the largest group, and post-PK astigmatism (31%) represented the second largest group of patients with irregular corneas who had completed the PROSE treatment. Patients with keratoconus had the greatest improvement in VA after PROSE fitting with an 88% improvement in the logarithm of the minimal angle of resolution vision. Patients with post-PK astigmatism had the greatest improvement in Ocular Surface Disease Index scores with a 79% improvement observed after PROSE fitting. Conclusions: PROSE scleral lenses offer improvements in the VA and function, and they could be an option for patients with irregular corneas who have failed conventional treatments before considering additional surgery.

Penetrating keratoplasty in infants with congenital glaucoma.

The efficacy of corneal transplantation in infants with corneal opacity secondary to congenital glaucoma has not been established. We retrospectively reviewed our results of nine penetrating keratoplasties performed on eight eyes of six infants who had multiple risk factors for poor prognosis: age <2 years at the time of grafting; uncontrolled glaucoma in four eyes; concurrent lensectomy, retinal, or glaucoma surgery in five eyes; aphakia in five eyes; and an acute perforation in one eye. Six of the nine grafts (67%) remained clear during a mean follow-up of 24 months (30 months in eyes with clear grafts). Development of ambulatory vision or better occurred in six of eight (75%) eyes after corneal transplantation and treatment of refractive errors and amblyopia. Graft failure occurred in three eyes—two from corneal decompensation, and one from homograft rejection. Complications included one total retinal detachment, one case of Streptococcus pneumoniae keratitis, and three cases that lost intraocular pressure control, requiring further glaucoma surgery. We conclude that useful vision can be achieved after penetrating keratoplasty even in some high-risk infants with congenital glaucoma.

Keratitis as a complication of bilateral, simultaneous radial keratotomy.

During a one-month period, we examined four patients referred for evaluation of probable microbial keratitis after bilateral, simultaneous radial keratotomy. Each patient had midstromal infiltrates compatible with microbial keratitis that involved one or more of the radial incisions. In two patients the keratitis was bilateral. All patients had been treated empirically with antibiotic agents; superficial cultures with cotton-tipped applicators and corneal scraping by inserting a platinum spatula into the radial incisions were negative. Corneal biopsy of one patient disclosed gram-positive rods and culture of the biopsy specimen grew diphtheroids. The infiltrates gradually resolved over a period of several months with intensive antibiotic therapy. Sight-threatening infectious keratitis can occur after radial keratotomy, and we believe that simultaneous bilateral ocular surgery of any kind should be discouraged.

Evaluation of intraocular lens power calculation formulas in the triple procedure

Purpose: To determine whether the choice of intraocular lens (IOL) power formula improves IOL power predictions and whether personalized constants within the IOL power formula are critical factors in improving refractive predictions after combined penetrating keratoplasty, cataract extraction, and IOL implantation. Methods: Records of 46 patients who had the triple procedure between January 1988 and December 1992 were evaluated using the SRK II, SRK/T, Holladay, and Hoffer Q formulas to predict the postoperative spherical equivalent refractions for implanted lens power. Calculations were carried out with and without the use of personalized constants. The predictive accuracy of each formula was assessed by comparing the actual postoperative spherical equivalent refractive error with that predicted by the formulas. The predictive error and the distribution of predictive errors were used to assess predictive accuracy. Results: There was no difference in the mean absolute predictive errors and the distribution of predictive errors for the four formulas evaluated (P < .05). The use of personalized formula constants significantly reduced the mean absolute predictive error for the SRK II, SRK/T, and Holladay formulas (P < .05) and approached significance for the Hoffer Q formula. Conclusion: The findings suggest that the choice of IOL power formula does not affect IOL power predictions in the corneal triple procedure; however, personalized constants within a formula appears to be a critical factor in improving postoperative refractive predictions.

PROSE Treatment in Atypical Ocular Graft-Versus-Host Disease.

Purpose To report a case of persistent epithelial defects in a patient with ocular chronic graft-versus-host disease that required coordinated modulation of systemic immunosuppressive treatment and overnight wear of Prosthetic Replacement of the Ocular Surface Ecosystem (BostonSight PROSE, Needham, MA) devices to achieve ocular surface healing. Case Report The case of a 38-year-old male patient who presented with a 2-year history of ocular chronic graft-versus-host disease, ocular burning, pain, light sensitivity, and a 3-week history of bilateral corneal epithelial defects is presented. Standard therapies and an initial PROSE treatment utilizing customized scleral lenses were unsuccessful in resolving his ocular complications. A second trial of PROSE treatment involving overnight wear of the devices in combination with increased systemic immunosuppressant therapy ultimately allowed ocular surface healing and improved his discomfort, vision, and quality of life. Conclusions Sight-threatening complications of ocular chronic graft-versus-host disease often require a multidisciplinary approach. Persistent corneal epithelial defects may require increased systemic immunosuppression and extension of PROSE treatment to overnight wear.

Optical Coherence Tomography of Corneal and Scleral Melts

BACKGROUND AND OBJECTIVE To compare the effectiveness of augmented superior oblique Z-tenotomy (SOZT) with fixed standard SOZT in canceling preoperative superior oblique overaction associated with A pattern anisotropia or V pattern in Browns syndrome. PATIENTS AND METHODS Sixteen consecutive patients with superior oblique overaction or Browns syndrome were treated by removal of a triangular piece of the superior oblique tendon near its insertion (augmented SOZT). Outcome was compared with 20 consecutive historical controls after standard SOZT. RESULTS The decrease in superior oblique overaction in the right and left eyes and fundus intorsion and the collapse of A pattern anisotropia were more significant for patients with superior oblique overaction (P = .003, P = .007, P = .05, P = .0015, respectively) and patients with Browns syndrome (P = .025, P = .03, and P = .05, respectively). No study patient with superior oblique overaction and A pattern anisotropia required reoperation compared with 5 of 14 controls (37.5%); rates for patients with Browns syndrome were 0 for the study group and 3 of 6 (50%) for the control group. CONCLUSIONS Augmented SOZT is superior to standard SOZT for correcting superior oblique overaction, intorsion, A or V pattern, and stereopsis. It is not associated with complications or reoperation. The size of the Z-tenotomy can be modified according to the intraoperative assessment to achieve symmetric results.