Allison R. Loh

Iron homeostasis and eye disease

BACKGROUND Iron is necessary for life, but excess iron can be toxic to tissues. Iron is thought to damage tissues primarily by generating oxygen free radicals through the Fenton reaction. METHODS We present an overview of the evidence supporting irons potential contribution to a broad range of eye disease using an anatomical approach. RESULTS Iron can be visualized in the cornea as iron lines in the normal aging cornea as well as in diseases like keratoconus and pterygium. In the lens, we present the evidence for the role of oxidative damage in cataractogenesis. Also, we review the evidence that iron may play a role in the pathogenesis of the retinal disease age-related macular degeneration. Although currently there is no direct link between excess iron and development of optic neuropathies, ferrous irons ability to form highly reactive oxygen species may play a role in optic nerve pathology. Lastly, we discuss recent advances in prevention and therapeutics for eye disease with antioxidants and iron chelators. GENERAL SIGNIFICANCE Iron homeostasis is important for ocular health.

Practice patterns in the management of fungal corneal ulcers

Purpose: The purpose of this study was to determine the practice patterns of ophthalmologists in the management of fungal corneal ulcers. Methods: In December 2007, a survey of 13 questions addressing the actual and preferred treatment of fungal ulcers was sent to the kera-net e-mail listserv facilitated by the Cornea Society. Results: Ninety-two respondents from North America, South America, Asia, Europe, and Australia participated by completing the electronic questionnaire. Natamycin was the most commonly used topical treatment for ulcers caused by filamentous fungi (96%) followed by amphotericin (75%) and voriconazole (63%). However, voriconazole was most often listed as the preferred topical treatment in an ideal world (79%) compared with 55% for natamycin. Approximately half of the respondents use combination topical therapy (56%) and the remainder monotherapy. The majority of respondents rescrape the epithelium at some time during the course of treatment, but the frequency of rescraping varied among the different topical treatments. The most common reasons cited for not using their preferred treatment were cost and a desire for further evidence to support preferred treatment. Conclusion: There appears to be significant variation in the management of fungal corneal ulcers. Although natamycin was the most commonly used treatment for ulcers caused by filamentous fungi, voriconazole was the most preferred as the ideal treatment. These results highlight the need for more evidence regarding the efficacy of the newer topical antifungals.

Cigarette smoking as a risk factor for uveitis

PURPOSE To determine the association between tobacco smoking history and uveitis. DESIGN Retrospective, case-control study. PARTICIPANTS A total of 564 patients with ocular inflammation seen in the Proctor Foundation uveitis clinic between 2002 and 2009, and 564 randomly selected patients seen in the comprehensive eye clinic within the same time period. METHODS A retrospective medical record review of all cases and controls. MAIN OUTCOME MEASURES A logistic regression analysis was conducted with ocular inflammation as the main outcome variable and smoking as the main predictor variable, while adjusting for age, gender, race, and median income. RESULTS The odds of a smoker having ocular inflammation were 2.2-fold that of a patient who had never smoked (95% confidence interval [CI], 1.7-3.0; P<0.001). All anatomic subtypes of uveitis were associated with a positive smoking history, with odds ratios (ORs) of 1.7 (95% CI, 1.2-2.4; P = 0.002) for anterior uveitis, 2.7 (95% CI, 1.4-5.6; P = 0.005) for intermediate uveitis, 3.2 (95% CI, 1.3-7.9; P = 0.014) for posterior uveitis, and 3.9 (95% CI, 2.4-6.1; P<0.001) for panuveitis. In patients with panuveitis and cystoid macular edema (CME), the OR was 8.0 (95% CI, 3.3-19.5; P<0.001) compared with 3.1 (95% CI, 1.8-5.2; P<0.001) for patients without CME. Patients with intermediate uveitis and CME also had a higher OR (OR 8.4; 95% CI, 2.5-28.8; P = 0.001) compared with patients without CME (OR 1.5; 95% CI, 0.6-3.8; P = 0.342). Patients with a smoking history were at greater odds of having infectious uveitis (OR 4.5; 95% CI, 2.3-9.0; P<0.001) than noninfectious uveitis (OR 2.1; 95% CI, 1.6-2.8; P<0.001), although both were associated with smoking. CONCLUSIONS A history of smoking is significantly associated with all anatomic subtypes of uveitis and infectious uveitis. The association was greater in patients with intermediate uveitis and panuveitis with CME compared with those without CME. In view of the known risks of smoking, these findings, if replicated, would give an additional reason to recommend smoking cessation in patients with uveitis.

Incidence Rates and Risk Factors for Ocular Complications and Vision Loss in HLA-B27-Associated Uveitis

PURPOSE To calculate the incidence rates of ocular complications and vision loss in HLA-B27-associated uveitis and to explore the effect of chronic inflammation on clinical outcomes. DESIGN Retrospective longitudinal cohort study. METHODS The clinical records of 99 patients (148 uveitis-affected eyes) with HLA-B27-associated uveitis seen at a tertiary care center were included. The main outcome measures were ocular complications (posterior iris synechiae, band keratopathy, posterior subcapsular [PSC] cataracts, ocular hypertension, hypotony, cystoid macular edema, and epiretinal membrane) and vision loss. Anterior chamber inflammation was defined as ≥1+ grade inflammation. Chronic uveitis was defined as persistent inflammation with relapse in <3 months after discontinuing treatment or requiring medications to suppress inflammation for >3 months after reviewing the patients entire clinical course. RESULTS The clinical course was most commonly acute/recurrent (75%) or chronic (20%). The most common complications to develop during follow-up were ocular hypertension (0.10/eye-year) and PSC cataracts (0.09/eye-year). In multivariate analysis, the presence of posterior synechiae at presentation, inflammation, corticosteroid-sparing therapy, corticosteroid injections, chronic disease, and male gender were associated with a statistically significant increased risk of developing vision loss (20/50 or worse). Chronic disease course was associated with a 7-fold increased risk of visual impairment (hazard ratio [HR] = 6.8, P < .0001). The presence of inflammation during follow-up was associated with an increased risk of developing visual impairment (HR = 6.2, P < .0001). In multivariate analysis, chronic disease course and topical corticosteroids were associated with an increased risk of developing any incident ocular complication (HR = 2.2, P = .04 and HR = 3.3, P = .01, respectively). CONCLUSIONS Poorly controlled inflammation was associated with the development of ocular complications including vision loss. Patients with chronic inflammation were also at greater risk of complications.

Fluocinolone Acetonide Intravitreal Implants in Vogt-Koyanagi-Harada Disease

Purpose: To describe the use of fluocinolone acetonide implants (Retisert) in Vogt-Koyanagi-Harada disease (VKH). Design: Interventional case series. Methods: Retrospective review of medical records. Results: Two patients with VKH requiring high-dose systemic corticosteroid therapy to control their inflammation and bilateral serous retinal detachments received bilateral fluocinolone acetonide implants. Upon tapering of systemic corticosteroids, one patient had recurrent serous retinal detachments and the other patient’s anterior chamber and vitreous inflammation returned. Conclusions: The authors’ experience with fluocinolone acetonide implants in VKH has been mixed with an inability to fully taper off of systemic corticosteroids.

Susceptibility testing and clinical outcome in fungal keratitis

Fungal keratitis causes significant morbidity, especially in tropical climates, and is notoriously difficult to manage. The choice of antifungal agent for fungal keratitis remains largely empirical, with no consensus on the role of susceptibility testing in guiding therapy. Studies suggest that susceptibility and outcome may be associated in systemic fungal infections with some dimorphic fungi,1 but this correlation may not exist for filamentous fungi or in ocular disease because of frequent topical dosing and high drug concentration. Given the availability of new topical medications, tailoring antifungal therapy based on microbial sensitivity is important.2 Here, we assess whether fungal susceptibility testing correlates with clinical outcomes in cases of fungal keratitis. This study was a retrospective case review of consecutive patients with culture proven fungal keratitis presenting to the Aravind Eye Hospital cornea clinic between March and July 2004. Of 98 consecutive patients, minimum inhibitory concentration (MIC) data was available for 90.3 Eighty-one corresponding charts were available, and 54 charts had follow-up of at least 3 weeks to allow determination of healing. All cases were …

Predictors of Matching in an Ophthalmology Residency Program

PURPOSE To examine the characteristics of US medical students applying for ophthalmology residency and to determine the predictors of matching. DESIGN A retrospective case series. PARTICIPANTS A total of 3435 medical students from the United States who applied to an ophthalmology residency program from 2003 to 2008 were included. METHODS Matched and unmatched applicants were compared and stratified by predictor variables, including United States Medical Licensing Examination (USMLE) Step 1 score, Alpha Omega Alpha (AOA) status, medical school reputation, and medical school geographic region. Differences in proportions were analyzed using the Fisher exact test. Logistic regression was used to determine the predictors of successful matching. MAIN OUTCOME MEASURES Successful matching to an ophthalmology program. RESULTS The majority of applicants (72%, 2486/3435) matched in ophthalmology. In multivariate analysis, AOA membership (odds ratio [OR], 2.6, P<0.0001), USMLE score (OR, 1.6; P<0.0001), presence of an ophthalmology residency at medical school (OR, 1.4; P = 0.01), top 25 medical school (OR, 1.4; P<0.03), top 10 medical school (OR, 1.6; P<0.02), and allopathic degree (OR, 4.0; P<0.0001) were statistically significant predictors of matching. Approximately 60% (1442/2486) of applicants matched to the same geographic region as their medical school. Applicants were more likely to match at a program in the same geographic region as their medical school than would be predicted by chance alone (P<0.0001). In multivariate analysis, higher USMLE score (OR, 0.9; P<0.0001) and top 10 medical school (OR, 0.7; P = 0.027) were statistically significant predictors of matching to outside the geographic region as ones medical school. CONCLUSIONS The majority of applicants applying for an ophthalmology residency position match successfully. Higher performance on quantitative metrics seems to confer an advantage for matching. The majority of applicants match at a residency program within the same geographic region as ones medical school.

Predictors of Matching in Ophthalmology Residency for International Medical Graduates

Interleukin-8 is an inflammatory cytokine that promotes angiogenesis and increases capillary leakage. The IL-8 rs4073 and VEGF rs699947 are promoter polymorphisms connected to transcriptional activity of the genes. The A allele in IL-8 rs4073 has been associated with higher levels of circulating and secreted IL-8, and a poorer response to bevacizumab in ovarian cancer. The C allele in VEGF rs699947 has been associated with higher VEGF production. In our patients, the C allele was associated with somewhat less CS gain. However, the A allele was more strongly associated with persisting macular fluid and more frequent reinjections. The reason for the possible dichotomous effect of this VEGF polymorphism on the anatomic and functional outcomes is unclear. Complement activity stimulates IL-8 production in endothelial and retinal pigment epithelial cells. The combination of a deficient regulation of alternative complement pathway and greater IL-8 production may lead to IL-8 stimulated angiogenesis and capillary leakage. The cumulative effect of the risk alleles suggests that IL-8 signaling may serve as a compensatory proangiogenic mechanism during anti-VEGF treatment. An explanation for the less producing VEGF genotype to require more injections could be that it maymake such potential compensatory mechanisms more active.

Amphotericin B and natamycin are not synergistic in vitro against Fusarium and Aspergillus spp. isolated from keratitis

Infectious keratitis is a major cause of monocular blindness worldwide.1 Although fungal ulcers are relatively uncommon in developed nations, they occur frequently in developing countries, especially those in tropical regions. In South India, up to half of infectious ulcers are fungal.2 Fungal ulcers are notoriously difficult to treat compared with bacterial ulcers, and physicians frequently use combination therapy.3 Amphotericin B and natamycin are two commonly used topical agents to treat filamentous fungal keratitis.3 However, combination therapy may increase the risk of potential drug toxicity as well as the cost of therapy. Currently, there are no data on whether natamycin and amphotericin B interact synergistically in vitro against filamentous fungi. Here, we investigate whether amphotericin B and natamycin interact synergistically in vitro when tested against Fusarium and Aspergillus spp. isolated from patients with fungal keratitis. Ten Fusarium spp. and ten Aspergillus spp. isolates were randomly selected from 98 consecutive cases of culture-positive fungal keratitis treated at Aravind Eye Hospital in South India. All patients underwent cornea culture and were treated with natamycin, …

Association of community antibiotic consumption with clinically active trachoma in rural Ethiopia

Community antibiotic utilization and its relationship with trachoma has been poorly characterized in areas with endemic trachoma. A survey of all drug-dispensing facilities in an area of rural Ethiopia was conducted. Antibiotic use was calculated using both retrospective and prospective methodology, and expressed as defined daily doses (DDDs). Overall antibiotic consumption estimates ranged from 2.91 to 3.07 DDDs per 1000 person days. Macrolide antibiotics accounted for 0.01 to 0.02 DDDs per 1000 person days. Each additional DDD of antibiotic use per 1000 person days was associated with a 15.0% (95% CI -19.7 to -10.3) decrease in the prevalence of clinically active trachoma among children under 10 years of age after adjusting for age, gender, altitude and the distance to nearest town. Increased background community antibiotic use may therefore be an aspect of socioeconomic development that can partially explain why trachoma prevalence has decreased in some areas in the absence of a trachoma program. The low volume of macrolide consumption in this area suggests that selection for nasopharyngeal pneumococcal macrolide resistance after mass azithromycin treatments likely has little clinical significance.