Thomas F. Mauger

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.

Optimization of wavefront-coded infinity-corrected microscope systems with extended depth of field

The depth of field of an infinity-corrected microscope system is greatly extended by simply applying a specially designed phase mask between the objective and the tube lens. In comparison with the method of modifying the structure of objective, it is more cost effective and provides improved flexibility for assembling the system. Instead of using an ideal optical system for simulation which was the focus of the previous research, a practical wavefront-coded infinity-corrected microscope system is designed in this paper by considering the various aberrations. Two new optimization methods, based on the commercial optical design software, are proposed to design a wavefront-coded microscope using a non-symmetric phase mask and a symmetric phase mask, respectively. We use polynomial phase mask and rational phase mask as examples of the non-symmetric and symmetric phase masks respectively. Simulation results show that both optimization methods work well for a 32 × infinity-corrected microscope system with 0.6 numerical aperture. The depth of field is extended to about 13 times of the traditional one.

Cholinergic sensitivity of irides from donors with various pathological conditions and lens implants

In vitro, iris contractions after muscarinic agonists were measured in mg of tension change and the concentration producing 50% of the response was expressed as EC50 mumol/l. Although the average EC50 value of carbachol in the iris sphincter of the donors with diabetes or Parkinsons disease did not change significantly when compared with the control, the maximum contraction of the tissue from the diseased state was increased significantly. Thus, in addition to the well known denervation supersensitivity of the iris-dilator, the iris-sphincter also develops adaptive sensitivity changes. Antimuscarinic drug treatment in some Parkinsons patients interfered with the estimation of supersensitivity in vitro studies. The enhanced response of carbachol at the low temperatures or the relative potency of carbachol and pilocarpine in the tissue obtained from the diseased donors was not significantly different from that of controls. Based on EC50 values, the potency of arecoline on the iris was 1/3 that of carbachol. Significantly lower EC50 values of carbachol were found in irides which were in contact with open loop type anterior chamber lens implants compared with those in contact with the closed loop anterior chamber lens implants. Maximum responses of irides to carbachol were less when the tissue was in contact with open loop lens compared with those in contact with closed loop anterior chamber implants. Irides from many donors having unilateral or bilateral replacement of the artificial lenses responded with EC50 of carbachol which was approximately equal to that of the contralateral eye. The maximum difference between EC50 values of the left and right iris was less than 5 fold.(ABSTRACT TRUNCATED AT 250 WORDS)

Design of high-performance adaptive objective lens with large optical depth scanning range for ultrabroad near infrared microscopic imaging

We report on the theory and design of adaptive objective lens for ultra broadband near infrared light imaging with large dynamic optical depth scanning range by using an embedded tunable lens, which can find wide applications in deep tissue biomedical imaging systems, such as confocal microscope, optical coherence tomography (OCT), two-photon microscopy, etc., both in vivo and ex vivo. This design is based on, but not limited to, a home-made prototype of liquid-filled membrane lens with a clear aperture of 8mm and the thickness of 2.55mm ~3.18mm. It is beneficial to have an adaptive objective lens which allows an extended depth scanning range larger than the focal length zoom range, since this will keep the magnification of the whole system, numerical aperture (NA), field of view (FOV), and resolution more consistent. To achieve this goal, a systematic theory is presented, for the first time to our acknowledgment, by inserting the varifocal lens in between a front and a back solid lens group. The designed objective has a compact size (10mm-diameter and 15mm-length), ultrabroad working bandwidth (760nm - 920nm), a large depth scanning range (7.36mm in air) - 1.533 times of focal length zoom range (4.8mm in air), and a FOV around 1mm × 1mm. Diffraction-limited performance can be achieved within this ultrabroad bandwidth through all the scanning depth (the resolution is 2.22 μm - 2.81 μm, calculated at the wavelength of 800nm with the NA of 0.214 - 0.171). The chromatic focal shift value is within the depth of focus (field). The chromatic difference in distortion is nearly zero and the maximum distortion is less than 0.05%.

Acanthamoeba and Stenotrophomonas maltophilia keratitis with fungal keratitis in the contralateral eye

Purpose The purpose of this study is to describe the diagnosis, course, and outcome of a case of Acanthamoeba and Stenotrophomonas keratitis with a fungal keratitis in the contralateral eye. Methods A case of Acanthamoeba and Stenotrophomonas keratitis was diagnosed with confocal microscopy and cultures with confocal diagnosis of fungal keratitis in the fellow eye. Results During the initial treatment of the Acanthamoeba and Stenotrophomonas keratitis, the contralateral eye developed a keratitis that demonstrated hyphae in the corneal stroma with confocal microscopy consistent with fungal keratitis. Conclusions Bilateral chronic keratitis cannot be assumed to be caused by the same organism and independent cultures, and confocal microscopy needs to be performed to direct appropriate therapy.

CORNEAL BURNS: A QUANTITATIVE COMPARISON OF ACID AND BASE

A quantitative comparison is made of the effects of two of the most completely dissociating representatives from the pH spectrum, sodium hydroxide and hydrochloric acid, on oxygen uptake by the corneal epithelium. Based on initial observations, a 6 to 1 time ratio in the exposure period (acid, 60 seconds; base, 10 seconds) was found necessary to localize and define similiar aerobic effects by the 2 agents on their concentration scales. A further dosage adjustment factor was required, a 5/1 concentration ratio of acid to base, to achieve near parity of the major depressive thresholds of those 2 agents, as well as to illustrate in the resulting graphical model sevel unique features of each in their aerobic effects on corneal tissue at lower concentrations.

Epithelial healing: quantitative monitoring of the cornea following alkali burn

Abstract A micropolarographic system was used as a quantitative means of monitoring the healing course of corneal epithelium following a 10 second exposure to 0.20 N sodium hydroxide solution. Concentrations of less than that strength produced inconsistent flux baselines due to incomplete damage to the epithelium, while higher concentrations commonly involved the stroma as well. Virtually complete epithelial destruction (down to the basement membrane) and reproducible flux baselines were found, however, with the 0.20 N induced lesion studied in detail here. The healing course following those exposures consisted of two well defined phases: an intial period of hypoflux lasting some 48 h before rising back up to the pre‐lesion baseline, followed then by a period of hyperflux lasting about 7 days before decreasing once again down to the pre‐lesion baseline. This oxygen flux sequence closely parallels certain sliding and mitotic phases of epithelial healing already established in the literature.

Familial peripheral keratopathy without PAX6 mutation.

Purpose: To describe the clinical features of a familial abnormality of the corneal stem cells and to investigate the role of PAX6 mutations in the affected family members. Methods: A family with multiple generations of peripheral keratopathy was evaluated. Because of the corneal phenotypic similarity to aniridia-related keratopathy, it was hypothesized that the affected patients might have a dominantly inherited mutation of PAX6 on chromosome 11. Commercial sequencing of germline DNA from 1 affected family member did not identify any PAX6 mutations in the exons or intron–exon boundary regions. Because the commercial analysis is not designed to identify PAX6 deletions, germline DNA was collected from 5 unaffected and 2 additional affected family members. DNA repeat markers in the region of PAX6 were analyzed to determine whether this chromosomal region segregates with the disease phenotype. Results: Affected family members with this autosomal dominant peripheral corneal abnormality showed evidence of progressive corneal stem cell dysfunction. Several individuals demonstrated corectopia, and 1 individual had ectropion uvea but no other iris or ocular abnormalities associated with aniridia. Genotyping data of affected and unaffected family members demonstrated that the PAX6 region does not segregate with the disease phenotype. Conclusions: The features of this autosomal dominant abnormality show some similarity to aniridia, although the classic characteristics of severe iris hypoplasia and macular hypoplasia are absent. Mutational screening and genotyping could not conclusively clarify a role for PAX6 in this disease phenotype, suggesting that it is a distinct clinical and genetic disease entity, not a variant of aniridia.

Corneal anesthetic abuse from the use of topical benzonatate (Tessalon Perle).

leveldin 5 of 14 young healthy (‘‘nonDED’’) study participants with modest dehydration. It seems that dehydration did not increase the tear osmolarity to the DED threshold in the majority of their subjects (9 of 14). It is possible that the subset showing a diagnostic hyperosmolarity level after dehydration may have had a starting tear osmolarity greater than a subclinical level for DED (308 mOsm/L) and therefore would have difficulties in maintaining homeostasis in the challenging conditions. Alternatively, is it possible that the hyperosmolarity was associated with the more obvious mechanisms of (marginally) increased tear evaporation or lowered production in this small group? It seems that no other control measurements of tear physiological status were undertaken in the study. One problem with the methodology adopted by these investigators, which reduces the relevance of their data to our measurements of ocular surface tear osmolarity in DED, is that their subjects were instructed to blink 3 times and squeeze their eyes shut to release fresh tear fluid and reconstruct the tear film architecture before tear fluid was collected. Although this is the procedure suggested by OcuSense, it is one that we did not follow in our collection of tear samples, because we were concerned that it could alter osmolarity by introducing fresh tears. This may not have reduced the effect of hydration but could have yielded a sample less representative of the resident ocular surface fluid measured in our investigation. In many studies of tear osmolarity in patients with DED, increased tear film osmolarity is a characteristic of DED in comparison with age-matched normal subjects. Although it is possible that some patients in both samples may have had a degree of dehydration at the time of measurement, hydration is unlikely to have been a systematic confounder in previous studies and does not belie the diagnostic value of osmolarity measurements in the disease. Addressing the second suggestion that chronic dehydration may have a role in DED, if subjects with chronic dehydration tend to exhibit tear hyperosmolarity, it is extremely likely that their ocular surfaces are not healthy. Hyperosmolarity is not simply a marker of the disease; in fact, many consider it a central pathogenic mechanism. Thus, if a patient exhibits hyperosmolarity because of dehydration, then it should still be concluded that the subject’s ocular surface has been compromised, not that hyperosmolarity has led to an incorrect DED diagnosis. It is important in any disease, such as DED, that displays a multifactorial etiology to consider any factors that may contribute to its development. The researchers’ suggestion of chronic dehydration should be borne in mind. It seems likely from the writers’ study that Tosm increased with dehydration and tracked alterations in Posm with comparable utility to USG and that the analysis of tear fluid using a device such as the TearLab osmolarity system may offer a new hydration assessment technique. But, at present, we are not convinced of the converse that failure to take into account the body’s hydration could lead to a misdiagnosis of DED when measurements of tear osmolarity are considered in the absence of assessments of plasma osmolarity levels. In DED, the chronic increase of the osmolality of the resident ocular surface tear film is a feature (and primary pathogenic mechanism) for the disease. The average increase in Tosm reported by these investigators with 3% change in hydration is moderate and does not produce the exceptionally high values observed in more severe DED subjects. The authors, in their letter, report an interesting finding that would merit study in greater detail, especially in relation to the initial state of the subjects’ tear film. One would expect that subjects with a compromised tear film may exhibit a greater increase in osmolarity when challenged. Financial disclosures/conflicts of interest: None reported.