Comparison of femtosecond laser-assisted keratoplasty versus conventional penetrating keratoplasty.

PURPOSE: To compare postoperative outcomes for femtosecond laser-assisted keratoplasty (FLAK) with conventional penetrating keratoplasty (PK). DESIGN: Retrospective, comparative surgical series. PARTICIPANTS: Fifty consecutive patients who underwent FLAK and 50 case-controlled patients that had PK at the Casey Eye Institute (Oregon Health & Science University, Portland, OR). METHODS: Data was collected for 50 consecutive cases that underwent zigzag incision FLAK and was compared with 50 subjects that had conventional blade trephine incision PK with similar age, diagnosis and concurrent ocular morbidities over a 2-year follow-up period. MAIN OUTCOME MEASURES: Topographic astigmatism, best spectacle-corrected visual acuity, uncorrected visual acuity, pinhole visual acuity, and the timing of selective suture removal (or adjustment) over various follow-up intervals up to 2 years postoperatively. RESULTS: Significantly lower topographic astigmatism was achieved in the FLAK group over the PK group in the 4- to 6-month follow-up period (P = 0.0324), which correlated well with significant earlier selective suture removal that occurred in that same group over both the 2- to 3-month (P = 0.0025) and 4- to 6-month (P = 0.0236) follow-up periods. This difference in astigmatism was no longer present at any other follow-up period up to 24 months postoperatively. The subset analysis of patients with keratoconus or post-LASIK ectasia did not show any difference in either astigmatism or visual acuity at any time. CONCLUSIONS: Compared with PKP, FLAK had significant improvement in astigmatism before but not after the 6 month postoperative follow-up period. Earlier suture removal was noted in the FLAK group. No significant improvement in best spectacle-corrected visual acuity was noted at any time point. There were no complications or difficulties with trephination in the FLAK procedure across a wide range of corneal pathologies.

Corrigendum to "The Role of Medications in Causing Dry Eye".

[This corrects the article DOI: 10.1155/2012/285851.].

Development and validation of a short global dry eye symptom index.

ABSTRACT we have developed and evaluated the repeatability of a short questionnaire based on a visual analog scale (VAS) to quantify the frequency and severity of symptoms of dry eye syndrome (DES). The "Symptom Assessment iN Dry Eye" (SANDE) questionnaire utilizes a 100 mm horizontal VAS technique to quantify patient symptoms of ocular dryness and/or irritation. Fifty-two subjects with DES were prospectively enrolled and followed-up at 2 and 4 months with repeated administrations of the SANDE questionnaire and clinical ocular surface evaluation. Subjects demonstrated a wide range of symptom scores indicative of the variability of the disease. Analyses comparing the repeatability of SANDE scores from baseline to the 2-month follow-up indicated a significant downward regression of scores toward the mean. In contrast, repeatability measures were consistently good for questionnaires administered within a few days of one another (ICC ranging from 0.53 to 0.76). Bland-Altman analysis demonstrated that 50% of repeated SANDE symptom scores were within 10 mm of each other, 80% were within 20 mm, and 95% were within less than 30 mm. These data describe good repeatability for the SANDE symptom score when repeated assessments are made within a few days. The results are encouraging and suggest that further refinement and testing of the SANDE questionnaire in larger populations may result in a reliable questionnaire to detect change in irritative symptoms over time.

Intravital microscopy of leukocyte-endothelial dynamics using the Heidelberg confocal laser microscope in scleritis and allergic conjunctivitis.

PURPOSE: To examine leukocyte-endothelial cell rolling and arrest in human ocular vessels overlying sites of inflammation in various ocular inflammatory diseases in comparison to normal controls using the Heidelberg confocal laser microscope, which provides images with greater clarity and resolution than the tandem scanning microscope that uses white light. METHODS: Healthy controls (n=8) and patients with active anterior scleritis (n=7) or allergic eye disease (n=4) were scanned using the Heidelberg confocal laser microscope (HRT II) with the Rostock cornea module attachment for a minimum of 5 min at a depth of 45-120 microm from the conjunctival epithelial surface. RESULTS: There was a marked increase in the number of rolling leukocytes in scleritis patients (534+/-119 cells per mm2/min) versus controls (6+/-6 cells per mm2/min; p=0.0002) or allergic patients (59+/-44 cells per mm2/min; p=0.009). No statistically significant increase was seen in allergic patients compared to controls (p=0.059). A similar pattern was seen in the number of arrested leukocytes in patients with scleritis (56+/-23 cells per mm2) in comparison to either those with allergic eye disease or controls (each=0 cells per mm2; p=0.02). CONCLUSIONS: Patients with scleritis have a significantly increased number of rolling and arrested leukocytes in superficial ocular vessels in comparison to patients with mild allergic conjunctivitis and controls. The image quality with this microscope is superior to prior studies with a scanning microscope.

Non-invasive detection of multinucleated giant cells in the conjunctiva of patients with sarcoidosis by in-vivo confocal microscopy.

AIM: To explore the use of in-vivo confocal microscopy (IVCM) as a potential non-invasive adjunctive tool for diagnosing sarcoidosis. METHODS: Conjunctivae were imaged using confocal microscopy in 10 patients with sarcoidosis and 27 control subjects. We utilized the ASL-1000 Scanning Confocal Microscope (Advanced Scanning Ltd., New Orleans, LA) and the Confoscan 3 (Nidek Co. Ltd., Gamagori, Japan). Two masked observers reviewed the in-vivo confocal images of the conjunctivae in these subjects. One masked observer was experienced in reviewing confocal images. The most striking and obvious feature seen in granulomatous inflammation on confocal microscopy is the presence of multinucleated giant cells (MGCs). RESULTS: Unmasked observation of the scans revealed MGCs in six of the 10 sarcoid patients and no MGCs in the controls. One experienced masked observer found MGCs in five of the 10 patients with sarcoidosis and had no false-positive results (Fisher's exact test, p = 0.001; specificity = 1; sensitivity = 50% for the diagnosis of sarcoidosis and 83% compared to the unmasked observer). The second less-experienced masked observer detected MGCs in three of the 10 patients and three of the 27 controls (11.1% of the controls) (p = 0.186; specificity = 0.89; sensitivity = 30% of all patients with sarcoidosis and 50% compared to the unmasked observer). CONCLUSIONS: The utilization of IVCM to visualize the basic histology and pathology in sarcoidosis of the conjunctiva is novel. Initial results indicate that trained observers can detect MGCs in granulomatous inflammation. The ASL-1000 microscope tends to have better resolution and deeper penetration of the conjunctiva compared with the Confoscan 3.

A time course microarray study of gene expression in the mouse lacrimal gland after acute corneal trauma.

PURPOSE: To investigate the effect of corneal trauma on gene expression in the lacrimal gland and to assess how many genes and what specific genes are regulated in response to corneal trauma. METHODS: A mouse model with acute corneal trauma was created with a chemical burn to the cornea with silver nitrate. Sixty-four female BALB/c mice at 12 weeks of age were randomly divided into eight groups, eight mice per group. The corneas of four mice in each group were bilaterally cauterized with silver nitrate, and another four time-matched mice were used as the control. The total RNA of the lacrimal gland was then extracted, at eight time points--0.5, 1, 3, 8, 24, 72, 120, and 360 hours--after the corneal burn, and gene expression was examined with using cDNA microarray technology. RESULTS: Evaluation of 15,065 genes with multiple array replications showed significantly altered expression in 3,799 genes at one or more of the eight time points. Of those, 1,528 were known genes and 2,271 were unknown. The analysis of known genes showed broad and long-lasting gene suppression in most functional gene groups, including housekeeping, energy metabolism, protein degradation, DNA and protein synthesis, and apoptosis-associated genes. Heat shock genes were upregulated beginning at the 8-hour time point, indicating a stress response. CONCLUSIONS: This study demonstrates that corneal trauma has profound effects on the regulation of gene expression in the lacrimal gland and may provide genetic evidence for a cornea-to-lacrimal gland feedback mechanism in dry eye.

Cluster analysis of patients with ocular surface disease, blepharitis, and dry eye.

OBJECTIVE: To develop a classification system for blepharitis and dry eye based on a classification-tree model of a large group of subjects who were given a variety of objective physiologic tests. METHODS: We evaluated 513 subjects, some healthy and some with blepharitis and dry eye,with tests for tear volume, tear flow, and tear turnover and the Schirmer test for dry eye. Meibomian gland function was evaluated by meibomian gland lipid expression for lipid volume and lipid viscosity, evaporation, and eyelid transillumination for meibomian gland drop out. We subjected these data to cluster analysis and formulated a classification tree. MAIN OUTCOME MEASURE: The outcome measure of this study was the statistically valid groups of subjects with and without ocular surface symptoms identified by their physiologic characteristics. RESULTS: Cluster analysis most successfully grouped subjects by initially dividing them into 2 groups based on the presence or absence of gland drop out and then by lipid viscosity and volume, Schirmer test results, and evaporation. The analysis created 9 categories. This division created an objective classification system that was found to have clinical relevance. Normal subjects were distributed across several groups. CONCLUSIONS: Using a classification tree, blepharitis and dry eye can be classified with objective physiologic tests into clinically relevant groups that have common characteristics. The analysis establishes the central role of meibomian gland dysfunction in blepharitis and demonstrates the diverse characteristics of the normal population.

In vivo confocal microscopy of keratic precipitates.

OBJECTIVE: To evaluate the heterogeneity of keratic precipitates (KP) in varying subtypes of uveitis by in vivo confocal microscopy (IVCM). METHODS: The KP were viewed with a scanning confocal microscope in patients (n = 33) who sought care at a tertiary referral uveitis service for immune-mediated and infectious forms of uveitis, including HLA-B27-associated uveitis, sarcoidosis, Vogt-Koyanagi-Harada syndrome, juvenile chronic arthritis, Fuchs heterochromic iridocyclitis, cytomegalovirus retinitis, herpes zoster ophthalmicus, ocular toxoplasmosis, and idiopathic uveitis. Images were captured and digitalized in real time. RESULTS: Forty-two eyes of 33 patients were examined in this study. Patient age ranged from 22 to 84 years, with a mean age of 49.4 years. Seventeen (52%) of the patients were women, and 16 patients (48%) were men. The KP ranged in diameter from 10 to 350 mum. We observed the following absolute and speculative outcomes: KP are markedly heterogeneous and variable as documented by IVCM; KP in individual patients are consistent throughout the cornea; the morphologic features of KP change across time; infectious vs noninfectious causes of uveitis seem to be readily distinguishable by using IVCM; and KP may have consistency for specific disease states and therefore may have diagnostic importance. CONCLUSIONS: To our knowledge, this is the first time that IVCM has been used to describe the architecture and heterogeneity of KP in uveitis. Such observations reveal a heterogeneity that could not be appreciated by conventional slitlamp microscopy and may have diagnostic relevance.

In vivo confocal microscopy: increased conjunctival or episcleral leukocyte adhesion in patients who wear contact lenses with lower oxygen permeability (Dk) values.

PURPOSE: Contact lens wear is known to threaten the health of the ocular surface. In vivo confocal microscopy (IVCM) to visualize leukocyte rolling and extravasation in inflammation was recently described. We tested the hypothesis that contact lens wear is associated with measurable inflammation in superficial vessels. METHODS: Leukocyte rolling and sticking (hallmarks of the inflammatory process) were recorded by IVCM. IVCM was performed on conjunctival or episcleral blood vessels bilaterally on 55 contact lens wearers (15 male, 40 female) and 22 non-contact lens wearers (8 male, 14 female). Data were analyzed in 2 ways. Considering each vessel as an independent variable resulted in 132 analyzable vessel segments (13 daily disposable contact lenses, 67 traditional contact lenses, 14 rigid gas-permeable lenses, and 38 controls). Considering each subject as an independent variable resulted in analyzable data for 47 subjects (5 daily disposable contact lens wearers, 22 traditional contact lens wearers, 5 rigid contact lens wearers, and 15 control patients). Free-flowing, sticking, and rolling cells were counted in the vessels. Multiple parameters including mean flow velocity, shear rate, rolling cells/mm/min, and sticking cells/mm were calculated. RESULTS: We found no significant difference in leukocyte adhesion between control patients and patients wearing daily disposable, traditional disposable, or rigid gas-permeable lenses in both types of statistical analyses. However, the data regarding vessel segments as an independent variable show that there were more rolling cells in patients who wore contact lenses with oxygen permeability values (Dk) less than 10 as compared to those who wore contact lenses with oxygen permeability values greater than 16 (P < 0.01) or compared to controls (P < 0.01). CONCLUSION: IVCM is a novel, powerful technique to recognize a critical but subclinical component of inflammation. Although our data indicate that contact lens wear does not markedly increase rolling and sticking of leukocytes in conjunctival or episcleral vessels, there may be subclinical inflammation in association with lenses with the lowest oxygen permeability.

Clinical characteristics of Acanthamoeba keratitis infections in 28 states, 2008 to 2011.

PURPOSE: The aim was to describe a geographically and clinically diverse sample of cases of Acanthamoeba keratitis (AK) and establish the risk factors for poor outcomes among patients with this disease. METHODS: We conducted a retrospective, population-based case series of 116 patients with AK identified through a national surveillance network. Data were collected via a medical record review by diagnosing ophthalmologists and by phone interviews with patients. Exact logistic regression modeling was used to determine risk factors for poor visual outcomes. RESULTS: Among patients with data available on contact lens use, it was found that 93.3% wore contact lenses. The median time from symptom onset to care seeking was 2 days, whereas the median time from symptom onset to diagnosis was 27 days. Keratoplasty was performed in 27 of 81 patients with available outcome data and was more likely in patients >40 years old [odds ratio (OR) 5.25, 95% confidence interval (CI) 1.49-21.92]. When adjusted for age, the risk factors for keratoplasty included the presence of a ring infiltrate (OR 40.00, 95% CI 3.58-447.0) or any sign of stromal invasion (OR 10.48, 95% CI 2.56-55.09). One-third of patients with available data on best-corrected visual acuity had a best-corrected visual acuity <20/200, with the presence of a ring infiltrate as the only significant predictor of this outcome when adjusted for age (aOR 3.45, 95% CI 1.01-12.31). CONCLUSIONS: AK remains challenging to diagnose. Consequently, patients with advanced disease are more likely to have poor outcomes, particularly if they are older. The increasing awareness of AK among general eye care providers may shorten referral times and potentially improve outcomes.

Acanthamoeba keratitis: a 12-year experience covering a wide spectrum of presentations, diagnoses, and outcomes.

Purpose. To review characteristics of confocal microscopy, clinical presentation, and clinical outcome in 372 cases of Acanthamoeba keratitis (AK) from 1999 to 2011. Methods. A retrospective case review was performed on 372 cases of AK diagnosed by confocal microscopy (CFM) at a single institution in Portland, Oregon, from 1999 to 2011. A numbered grading system was devised for describing the relative microscopic severity of the AK infections detected. Results. "grade 1," 94 as "grade 2," 40 as "grade 3," and 62 as "grade 4." Peak incidences occurred during 2000-2002 and 2005-2007. Seasonal variation was noted, with a peak during summer months. For the 231 cases with complete records, 64% indicated a history of soft contact lens use. Nine progressed to multiple failed penetrating keratoplasties (PKPs) or enucleation. Conclusion. We report an average of 31 new cases of AK per year from 1999 to 2011. This figure equates to 10.3 new cases/1,000,000/year for the Portland metropolitan area. Patients diagnosed with AK exhibited a wide spectrum of clinical and microscopic characteristics. Soft contact lens use remained the single largest risk factor.

The role of medications in causing dry eye.

The purpose of this paper is to review the possible role of polypharmacy in causing dry eye disease (DED), reflecting the complex interactions and complications associated with the use of multiple systemic and topical ocular medications. The pharmacological, physiological, anatomical, and histological mechanisms causing dry mouth differ little from those causing dry eye. Oral polypharmacy is the most common cause of dry mouth, but has not been investigated as a cause of dry eye. Topical ocular polypharmacy has been shown to cause DED. Information on drugs that likely cause or aggravate DED and the controversial role of preservatives in topical ocular medications are examined. Systemic or topical ocular medications and preservatives used in topical ocular drugs may cause dry eye through the drug's therapeutic action, ocular surface effects, or preservatives, and the effects probably are additive. Long-term use of topical ocular medications, especially those containing preservatives such as BAK, may play an important role in DED and the role of polypharmacy needs further study. We review possible ways to decrease the risk of medication-related dry eye.

Femtosecond laser-assisted keratoplasty in failed penetrating keratoplasty and globe trauma.

PURPOSE: To demonstrate feasibility and present postoperative outcomes for femtosecond laser-assisted keratoplasty (FLAK) in the setting of previous failed conventional penetrating keratoplasty (PK) and previous open-globe trauma with corneal laceration. METHODS: In this retrospective case series, data were collected for 12 consecutive patients at the Casey Eye Institute (Oregon Health and Science University, Portland, OR) with the primary diagnosis of either failed PK or open-globe trauma with corneal laceration that underwent zigzag incision FLAK. Outcome measures included topographic astigmatism, best spectacle-corrected visual acuity, uncorrected visual acuity, pinhole visual acuity, intraocular pressure, and timing of selective suture removal (or adjustment) over various follow-up intervals up to 18 months postoperatively. RESULTS: Mean follow-up was 10.42 months. Mean postoperative topographic astigmatism ranged between 3.56 and 6.81 diopters (D). Mean best spectacle-corrected visual acuity (BSCVA) in logarithm of minimal angle of resolution (logMAR) equivalents ranged between 0.18 and 0.61 as compared with 1.28 for preoperative BSCVA (P = 0.0064). Thirty-three percent (4 of 12) of patients had significantly increased intraocular pressure develop during the first year of follow-up that required glaucoma therapy. No adverse events or complications occurred as a result of either the femtosecond laser procedure itself or during the transportation of the patient from the laser suite to the operating room. CONCLUSIONS: FLAK is a feasible transplantation technique in the setting of previous failed PK and open-globe trauma with corneal laceration. Significant globe pressure associated with laser applanation did not cause rupture of old corneal wounds among our case series. Postoperative astigmatism is within previous reported limits in the literature under varying suturing techniques. Development of ocular hypertension within 1 year of follow-up was comparable with historically reported rates for PK in the setting of previous trauma and failed grafts.

Laser in situ keratomileusis versus long-term contact lens wear: decision analysis.

PURPOSE: To compare the risk for vision loss from laser in situ keratomileusis (LASIK) versus long-term contact lens wear using decision analysis. SETTING: Oregon Health & Science University, Portland, Oregon, USA. METHODS: Based on previously published data, a decision tree was constructed using Markov modeling to calculate the probability of vision loss from LASIK versus contact lenses over time. An outcome variable, visual acuity-adjusted life-year (VALY), was defined to account for timing and severity of vision loss. The VALYs were tallied over a 30-year simulation to determine whether the risk for vision loss with contacts exceeded that with LASIK. Sensitivity analyses were performed to test the effect of changes in key variables including probability of contact lens-related keratitis, probability of ectasia after LASIK, and probability of early post-LASIK vision loss. RESULTS: The model's conclusions were highly sensitive to changes in several variables tested, especially risk for post-LASIK ectasia, risk for early vision loss after LASIK, and risk for contact lens-related keratitis (which correlated with type of lenses worn). Rigid gas-permeable lenses were safer than LASIK in every analysis. The safety of LASIK exceeded that for daily-wear soft lenses only when assumptions were most favorable to LASIK, whereas the safety of LASIK always exceeded that for extended-wear lenses except when assumptions were least favorable to LASIK. CONCLUSION: This decision analysis found that the risk for vision loss associated with LASIK and with long-term contact lens wear might be closer than generally assumed.

Condition-specific coregulation with cis-regulatory motifs and modules in the mouse genome.

Deciphering genetic regulatory codes remains a challenge. Here, we present an effective approach to identifying in vivo condition-specific coregulation with cis-regulatory motifs and modules in the mouse genome. A resampling-based algorithm was adopted to cluster our microarray data of a stress response, which generated 35 tight clusters with unique expression patterns containing 811 genes of 5652 genes significantly altered. Database searches identified many known motifs within the 3-kb regulatory regions of 40 genes from 3 clusters and modules with six to nine motifs that were commonly shared by 60-100% of these genes. The upstream regulatory region contained the highest frequency of these common motifs. CisModule program predictions were comparable with the results from database searches and found four potentially novel motifs. This result indicates that these motifs and modules could be responsible for gene coregulation of the stress response in the lacrimal gland.