Alfonso Iovieno

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.

Intracorneal ring segments implantation followed by same-day photorefractive keratectomy and corneal collagen cross-linking in keratoconus.

PURPOSE To evaluate the efficacy of intrastromal corneal ring segments implantation followed by same-day photorefractive keratectomy (PRK) and ultraviolet-A/riboflavin collagen cross-linking (CXL) in patients with keratoconus. METHODS Four patients (five eyes) were included in the study. All patients first underwent femtosecond laser-enabled placement of intracorneal ring segments (Intacs, Addition Technology). Uncorrected (UDVA) and corrected distance visual acuity (CDVA) and keratometry readings remained stable for 6 months. Same-day PRK and CXL were subsequently performed in all patients. RESULTS Six months after Intacs plus PRK/CXL, significant improvements were noted for UDVA, CDVA, spherical equivalent refraction, keratometry, and total aberrations. No patient lost lines of CDVA or developed haze. CONCLUSIONS The combination of intracorneal ring segments implantation followed by sequential same-day PRK/CXL may be a reasonable option for improving visual acuity in select patients with keratoconus.

In vivo characterization of doxycycline effects on tear metalloproteinases in patients with chronic blepharitis

Purpose Matrix metalloproteinases (MMPs) have a role in the pathogenesis of rosacea-associated chronic blepharitis. Doxycycline is largely used as a treatment for recalcitrant chronic blepharitis. It has been shown in vitro that doxycycline inhibits MMPs activation. The aim of this study was to investigate in vivo the effect of doxycycline in modulating MMPs in patients with chronic idiopathic blepharitis. Methods Eight patients (6 male, 2 female; mean age 45.7±17.5 years) were included in the study. Doxycycline (100 mg) was administered orally, twice a day, for 2 weeks and once a day for an additional 2 weeks. Clinical signs and symptoms were evaluated and scored (0–3) at baseline and after 4 weeks. Total sign (TSS) and total symptom (TSyS) scores were calculated. Tear samples and conjunctival impression cytologies were collected at baseline and after 4 weeks of treatment to evaluate MMP-9 and TIMP-1 expression and activity. Results An improvement in TSS (4.5±1.1 vs 2.7±1.5) and TSyS (6.6±1.3 vs. 3.1±1.9) was observed after 4 weeks, with significant amelioration of hyperemia, marginal blepharitis, and superficial punctuate keratopathy. Zymography revealed a decrease of MMP-9 activity after 4 weeks. MMP-9 mRNA and protein levels did not change, while an upregulation of TIMP-1 expression was observed. Conclusions This study suggests that 4-week treatment with doxycycline significantly improved symptoms and signs in patients with chronic blepharitis in association with a decrease in MMP-9 activity. Upregulation of TIMP-1 is proposed as a possible mechanism of MMP-9 inactivation. (Eur J Ophthalmol 2009; 19: 708–16)

Corneal stromal demarcation line after accelerated crosslinking using continuous and pulsed light

Purpose To evaluate and compare the depth of corneal stromal demarcation line after accelerated collagen crosslinking (CXL) using continuous and pulsed light ultraviolet‐A (UVA) exposure. Setting Department of Ophthalmology, Arcispedale Santa Maria Nuova, Reggio Emilia, Italy. Design Retrospective case series. Methods Patients with progressive keratoconus were assigned to 1 of 2 treatment protocols using the same irradiation device for accelerated CXL. Patients assigned to Group A received accelerated CXL using continuous UVA light exposure at 30 mW/cm2 for 4 minutes. Patients assigned to Group B received accelerated CXL using pulsed UVA light with 8 minutes (1 second on/1 second off) of UVA exposure at 30 mW/cm2 and energy dose of 7.2 J/cm2. One month after surgery, corneal stromal demarcation line depth was measured by 2 independent observers using anterior segment optical coherence tomography (AS‐OCT). Results A total of 60 patients were assessed. Corneal stromal demarcation line was easily identified on AS‐OCT scans in all eyes by both observers. The mean depth of stromal demarcation line was 149.32 ± 36.03 &mgr;m in Group A and 213 ± 47.38 &mgr;m in Group B. The difference in stromal demarcation line depth between groups was statistically significant (P < .001). Conclusions Using accelerated CXL, the corneal stromal demarcation line was significantly deeper using pulsed rather than continuous light exposure. Financial Disclosure No author has financial or proprietary interest in any material or method mentioned.

Accelerated Corneal Collagen Cross-Linking Using Topography-Guided UV-A Energy Emission: Preliminary Clinical and Morphological Outcomes

Purpose. To assess the clinical and morphological outcomes of topography-guided accelerated corneal cross-linking. Design. Retrospective case series. Methods. 21 eyes of 20 patients with progressive keratoconus were enrolled. All patients underwent accelerated cross-linking using an ultraviolet-A (UVA) exposure with an energy release varying from 7.2 J/cm2 up to 15 J/cm2, according to the topographic corneal curvature. Uncorrected (UDVA) and corrected (CDVA) distance visual acuity, topography, in vivo confocal microscopy (IVCM), and anterior segment optic coherence tomography (AS-OCT) were evaluated preoperatively and at the 1, 3, 6, and 12 months postoperatively. Results. 12 months after surgery UDVA and CDVA did not significantly vary from preoperative values. The average topographic astigmatism decreased from −4.61 ± 0.74 diopters (D) to −3.20 ± 0.81 D and coma aberration improved from 0.95 ± 0.03 μm to 0.88 ± 0.04 μm after surgery. AS-OCT and IVCM documented differential effects on the treated areas using different energies doses. The depths of demarcation line and keratocyte apoptosis were assessed. Conclusions. Preliminary results show correspondence between the energy dose applied and the microstructural stromal changes induced by the cross-linking at various depths in different areas of treated cornea. One year after surgery a significant reduction in the topographic astigmatism and comatic aberration was detected. None of the patients developed significant complications.

Descemetorhexis Without Graft Placement for the Treatment of Fuchs Endothelial Dystrophy: Preliminary Results and Review of the Literature

Purpose: To report our preliminary experience with a central descemetorhexis without graft placement in Fuchs endothelial corneal dystrophy (FECD) and to review the existing literature on the topic. Methods: A 4-mm central descemetorhexis was performed in 5 patients (4 women, 1 man; mean age: 69.8 ± 8.6 yrs; range: 57–78 yrs) with FECD. All patients had central confluent guttae, undetectable central endothelial cell count, healthy peripheral corneal endothelium, no clinically evident bullous keratopathy, and no ocular comorbidities. In 3 patients, the procedure was combined with phacoemulsification and intraocular lens implantation. Results: All patients completed at least 6 months of postoperative follow-up (mean follow-up 9 ± 2.5 mo; 7–13 mo). Endothelial repopulation of the central stroma was completed in all patients by the third month. Corneal clarity was achieved in 4 of 5 patients. The patient with persistent edema and haze had the highest preoperative central pachymetry. A final improvement in corrected visual acuity was achieved in 4/5 patients. A reduction in preoperative central pachymetry was observed in all cases. All patients developed deep stromal opacities around the margin of the descemetorhexis, which did not resolve over the follow-up time. Abnormal corneal topography and irregular astigmatism developed in 3 of 5 patients; these patients achieved 20/20 corrected distance visual acuity with rigid gas-permeable contact lens fitting. Conclusions: In partial concordance with previous studies, preliminary outcomes of a central descemetorhexis in FECD performed without endothelial graft placement seemed rather unpredictable. Baring of central stroma may trigger a variable wound-healing response with subsequent posterior stromal scarring and topographical irregularity.

Bromfenac ophthalmic solution 0.09% as an adjunctive therapy to topical steroids after cataract surgery in pseudoexfoliation syndrome.

Purpose To study with laser flare photometry the antiinflammatory effect of bromfenac added to a topical steroid versus a topical steroid alone in patients with pseudoexfoliation (PXF) syndrome after cataract surgery. Setting Ophthalmology Unit, Santa Maria Nuova Hospital, Reggio Emilia, Italy. Design Randomized clinical trial. Methods Patients with cataract and clinical signs of PXF were randomized to dexamethasone 0.1% and tobramycin 0.3% ophthalmic solution (Group 1) or with the adjunct of bromfenac ophthalmic solution 0.09% (Group 2). All patients were examined on the day of surgery (baseline) and postoperatively at 1, 3, 7, and 30 days. Laser flare photometry was used to quantify anterior chamber inflammation and optical coherence tomography to measure macular thickness. Results Sixty‐two patients were included. Postoperatively, the mean flare was 31% lower in Group 2 than in Group 1 at 3 days (11.92 ph/msec ± 8.14 [SD] versus 17.13 ± 9.03 ph/msec; P = .025) and 43% lower at 7 days (10.77 ± 6.17 ph/msec versus 18.72 ± 12.37 ph/msec; P = .003). There were no significant differences in postoperative visual acuity, symptoms, or ocular pain between groups. The mean macular thickness 1 month after surgery was increased in Group 1 but not Group 2; the difference between groups was significant at 4 weeks (P = .03). The incidence of intraretinal cysts was higher in Group 1 (n = 4) than in Group 2 (n = 0). Conclusion The addition of bromfenac to topical steroids after cataract surgery in eyes with PXF was associated with greater reductions in inflammation than steroids alone. Financial Disclosure None of the authors has a financial or proprietary interest in any material or method mentioned.

Therapeutic effect of topical 5-fluorouracil in conjunctival squamous carcinoma is associated with changes in matrix metalloproteinases and tissue inhibitor of metalloproteinases expression.

Purpose: To evaluate matrix metalloproteinases (MMP)-2, MMP-9, and tissue inhibitor of metalloproteinase (TIMP)-1 expression in a case of conjunctival intraepithelial squamous cell carcinoma (SCC) treated with topical 5-fluorouracil (5-FU) chemotherapy. Methods: Clinicopathologic case report. Results: A 71-year-old male patient presented with an intraepithelial conjunctival SCC. Because of a recurrence, he was placed on topical 5-FU for 4 weeks that ultimately led to a complete resolution of the disease. Conjunctival biopsies, impression cytologies, and tear samples were taken from the mass and the contralateral healthy eye. An overexpression of MMP-2, MMP-9, and TIMP-1 was observed in the tumor by immunohistochemistry. Clinical resolution of the neoplasm obtained using topical 5-FU was accompanied by a reduction in the expression of MMP-2, MMP-9, and TIMP-1 in tears and dysplastic conjunctival epithelium. Conclusions: In our case report, we have shown that gelatinase and TIMP-1 are unregulated in conjunctival SCC and can be monitored as a marker of response to topical chemotherapy. Further studies are required to define the role of MMPs in growth and resolution of ocular tumors.

Outcomes of repeat endothelial keratoplasty in patients with failed Descemet stripping endothelial keratoplasty.

Purpose: To report the outcomes of repeat endothelial keratoplasty (EK) in patients with failed Descemet stripping endothelial keratoplasty (DSEK). Methods: The clinical records of patients with failed DSEK who underwent repeat EK surgery at a single institution were reviewed. Results: A total of 20 eyes of 20 patients (8 men and 12 women) were included. The mean age at initial DSEK surgery was 69.9 ± 11.9 years (range, 41–83 years). The causes of DSEK failure included progressive endothelial failure (8 eyes; 40%), primary graft failure (8 eyes; 40%), and endothelial rejection (4 eyes; 20%). The mean duration from primary DSEK to repeat EK was 13.1 ± 10.3 months (range, 2–33 months). Removal of the failed DSEK donor disc was performed in all eyes. Mean preoperative corrected distance visual acuity (logMAR) before repeat EK surgery was 1.76, and this improved to 0.5 (P < 0.001) at the final follow-up at 27 months. Three eyes had limited corrected distance visual acuity secondary to ocular comorbidities (age-related macular degeneration and advanced glaucomatous optic neuropathy). Conclusions: Repeat EK in patients with DSEK failure is an effective treatment modality. This is the preferred management option compared with penetrating keratoplasty because the advantages of EK surgery are maintained with repeat EK surgery.