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To demonstrate the effects of prolonged silent reading on tear film and ocular surface parameters.Prospective, observational clinical study.A total of 177 patients with dry eye and 34 normal controls aged 50 years and older.After evaluating symptoms using the Ocular Surface Disease Index (OSDI) questionnaire, the following tests were performed in consecutive order: automated noninvasive tear break-up time (TBUT), surface asymmetry and regularity indices, Schirmer's testing without anesthesia, corneal staining using fluorescein, and conjunctival staining using lissamine green. The participants were then asked to read a 30-minute validated passage silently. The tests were repeated after the reading task.Changes in tear film and ocular surface parameters after reading.All parameters, with the exception of surface asymmetry index, worsened after the reading task in patients with dry eye and in controls. The worsening reached a statistical significance for corneal and conjunctival staining in the dry eye group (P0.001) and for corneal staining in the control group (P0.01). At baseline, OSDI scores correlated only with corneal and conjunctival staining scores (r = 0.19, P = 0.006 and r = 0.27, P0.001). Among postreading measurements, baseline OSDI scores correlated with TBUT (r = -0.15, P = 0.03) in addition to corneal and conjunctival staining (r = 0.25, P0.001 and r = 0.22, P = 0.001). Changes in TBUT and Schirmer's test correlated significantly with their respective baseline values (r = -0.61, P0.001 and r = -0.44, P0.001), indicating that the more unstable the tear film and the lower the aqueous tear secretion, the worse they became after the prolonged reading task. Worsening in corneal staining directly correlated with the baseline conjunctival staining (r = 0.17, P = 0.02) and surface regularity index (r = 0.21, P = 0.01).Evaluating tear film and ocular surface parameters at rest may miss clinical findings brought about by common everyday tasks such as reading, leading to discordance between patient-reported symptoms and clinician-observed signs. Quantifying dry eye after visually straining activities such as prolonged silent reading may help better understand patient symptomatology.

Abnormal nerve regeneration often follows corneal injury, predisposing patients to pain, dry eye and vision loss. Yet, we lack a mechanistic understanding of this process. A key event in corneal wounds is the differentiation of keratocytes into fibroblasts and scar-forming myofibroblasts. Here, we show for the first time that regenerating nerves avoid corneal regions populated by myofibroblasts in vivo. Recreating this interaction in vitro, we find neurite outgrowth delayed when myofibroblasts but not fibroblasts, are co-cultured with sensory neurons. After neurites elongated sufficiently, contact inhibition was observed with myofibroblasts, but not fibroblasts. Reduced neurite outgrowth in vitro appeared mediated by transforming growth factor beta 1 (TGF-β1) secreted by myofibroblasts, which increased phosphorylation of collapsin response mediating protein 2 (CRMP2) in neurons. The significance of this mechanism was further tested by applying Mitomycin C after photorefractive keratectomy to decrease myofibroblast differentiation. This generated earlier repopulation of the ablation zone by intra-epithelial and sub-basal nerves. Our findings suggest that attaining proper, rapid corneal nerve regeneration after injury may require blocking myofibroblast differentiation and/or TGF-β during wound healing. They also highlight hitherto undefined myofibroblast-neuron signaling processes capable of restricting neurite outgrowth in the cornea and other tissues where scars and nerves co-exist.

We report on a pathway for Gabor domain optical coherence microscopy (GD-OCM)-based metrology to assess the donor’s corneal endothelial layers ex vivo. Six corneas from the Lions Eye Bank at Albany and Rochester were imaged with GD-OCM. The raw 3-D images of the curved corneas were flattened using custom software to enhance the 2-D visualization of endothelial cells (ECs); then the ECs within a circle of 500-μm-diameter were analyzed using a custom corner method and a cell counting plugin in ImageJ. The EC number, EC area, endothelial cell density (ECD), and polymegethism (CV) were quantified in five different locations for each cornea. The robustness of the method (defined as the repeatability of measurement together with interoperator variability) was evaluated by independently repeating the entire ECD measurement procedure six times by three different examiners. The results from the six corneas show that the current modality reproduces the ECDs with a standard deviation of 2.3% of the mean ECD in every location, whereas the mean ECD across five locations varies by 5.1%. The resolution and imaging area provided through the use of GD-OCM may help to ultimately better assess the quality of donor corneas in transplantation.

To identify the microstructural modification of the corneal layers during the course of the disease, optical technologies have been pushing the boundary of innovation to achieve cellular resolution of deep layers of the cornea. Gabor-domain optical coherence microscopy (GD-OCM), an optical coherence tomography-based technique that can achieve an isotropic of ∼2-μm resolution over a volume of 1 mm×1 mm×1.2 mm, was developed to investigate the microstructural modifications of corneal layers in four common corneal diseases. Since individual layer visualization without cutting through several layers is challenging due to corneal curvature, a flattening algorithm was developed to remove the global curvature of the endothelial layer and display the full view of the endothelium and Descemet’s membrane in single en face images. As a result, GD-OCM revealed the qualitative changes in size and reflectivity of keratocytes in Fuchs endothelial corneal dystrophy (FECD), which varied by the degree of disease. More importantly, elongated shape and hyperactivation characteristics of keratocytes, associated with the early development of guttae, appeared to start in the posterior stroma very early in the disease process and move toward the anterior stroma during disease progression. This work opens a venue into the pathogenesis of FECD.

A Gabor-domain optical coherence microscope (GDOCM) with 2-micrometer invariant lateral and axial resolutions and a working distance of 15 mm was developed for 3D imaging of corneal tissue over a 1 mm2 field of view. The increased working distance over the previous in-contact implementation enables imaging of corneal tissue inside the viewing chamber in which corneas are stored after recovery from donors. The GDOCM system was used to image excised human corneas. 3D images of the cornea were acquired by imaging through the PMMA viewing chamber. The images achieved cellular resolution in the volume being imaged. Due to the curvature of the cornea, the endothelium, a single layer of cells lining the posterior surface of the cornea, cannot be viewed in a single en face image. A flattening algorithm was implemented to obtain an en face view of the endothelium. The GDOCM images were compared with those acquired with a specular microscope commonly used in eye banks for endothelial evaluation, and the endothelial cell density was assessed for both sets of images. A key advantage of GDOCM is the capability to image the entire thickness of the cornea in 3D with cellular resolution over a large field of view.

Purpose The purpose of this study was to assess the educational needs in geriatric care among practicing and training eye care providers at a single academic institution, the Flaum Eye Institute, at the University of Rochester Medical Center. Methods Data were collected using a voluntary and anonymous electronic survey that was distributed to 35 training and practicing eye care providers. Results Of the 35 distributed surveys, 27 (77%) were returned. Respondents included 6 residents-in-training and 17 practicing providers, based on those who reported demographics. Overall, respondents reported that most of their patients were older than 65 years (mean, 66.4%). Notably, 63% of providers felt they received very little to no prior education in geriatric care. Only 46.4% reported having a moderate level of interest in geriatric issues. While respondents reported high confidence levels in many geriatric domains, they reported moderate to low confidence levels in several others, including conducting cognitive and functional assessments, assessing and reducing the risk for falls and driving accidents, recognizing depression, and understanding the roles of long-term care and home services, social supports, and geriatric rehabilitation. Differences were also observed in confidence levels between residents-in-training and practicing providers in several geriatric domains. Conclusion At this single academic institution, current practicing and training ophthalmologists reported having limited prior education in geriatric care and identified many opportunities for geriatric education. While larger-scale studies need to be conducted to produce more generalizable results, this pilot study serves as a guide to augment geriatric education and training of ophthalmologists and improve the quality of eye care for the rapidly growing aging U.S. population.

Significance: An accurate, automated, and unbiased cell counting procedure is needed for tissue selection for corneal transplantation. Aim: To improve accuracy and reduce bias in endothelial cell density (ECD) quantification by combining Gabor-domain optical coherence microscopy (GDOCM) for three-dimensional, wide field-of-view (1 mm2) corneal imaging and machine learning for automatic delineation of endothelial cell boundaries. Approach: Human corneas stored in viewing chambers were imaged over a wide field-of-view with GDOCM without contacting the specimens. Numerical methods were applied to compensate for the natural curvature of the cornea and produce an image of the flattened endothelium. A convolutional neural network (CNN) was trained to automatically delineate the cell boundaries using 180 manually annotated images from six corneas. Ten additional corneas were imaged with GDOCM and compared with specular microscopy (SM) to determine performance of the combined GDOCM and CNN to achieve automated endothelial counts relative to current procedural standards. Results: Cells could be imaged over a larger area with GDOCM than SM, and more cells could be delineated via automatic cell segmentation than via manual methods. ECD obtained from automatic cell segmentation of GDOCM images yielded a correlation of 0.94 (p

Recent work in vitro has shown that fibroblasts and myofibroblasts have opposing effects on neurite outgrowth by peripheral sensory neurons. Here, we tested a prediction from this work that dampening the fibrotic response in the early phases of corneal wound healing in vivo could enhance reinnervation after a large, deep corneal injury such as that induced by photorefractive keratectomy (PRK). Since topical steroids and Mitomycin C (MMC) are often used clinically for mitigating corneal inflammation and scarring after PRK, they were ideal to test this prediction. Twenty adult cats underwent bilateral, myopic PRK over a 6 mm optical zone followed by either: (1) intraoperative MMC (n = 12 eyes), (2) intraoperative prednisolone acetate (PA) followed by twice daily topical application for 14 days (n = 12 eyes), or (3) no post-operative treatment (n = 16 eyes). Anti-fibrotic effects of MMC and PA were verified optically and histologically. First, optical coherence tomography (OCT) performed pre-operatively and 2, 4 and 12 weeks post-PRK was used to assess changes in corneal backscatter reflectivity. Post-mortem immunohistochemistry was then performed at 2, 4 and 12 weeks post-PRK, using antibodies against α-smooth muscle actin (α-SMA). Finally, immunohistochemistry with antibodies against βIII-tubulin (Tuj-1) was performed in the same corneas to quantify changes in nerve distribution relative to unoperated, control cat corneas. Two weeks after PRK, untreated corneas exhibited the greatest amount of staining for α-SMA, followed by PA-treated and MMC-treated eyes. This was matched by higher OCT-based stromal reflectivity values in untreated, than PA- and MMC-treated eyes. PA treatment appeared to slow epithelial healing and although normal epithelial thickness was restored by 12 weeks-post-PRK, intra-epithelial nerve length only reached ∼1/6 normal values in PA-treated eyes. Even peripheral cornea (outside the ablation zone) exhibited depressed intra-epithelial nerve densities after PA treatment. Stromal nerves were abundant under the α-SMA zone, but appeared to largely avoid it, creating an area of sub-epithelial stroma devoid of nerve trunks. In turn, this may have led to the lack of sub-basal and intra-epithelial nerves in the ablation zone of PA-treated eyes 4 weeks after PRK, and their continuing paucity 12 weeks after PRK. Intra-operative MMC, which sharply decreased α-SMA staining, was followed by rapid restoration of nerve densities in all corneal layers post-PRK compared to untreated corneas. Curiously, stromal nerves appeared unaffected by the development of large, stromal, acellular zones in MMC-treated corneas. Overall, it appears that post-PRK treatments that were most effective at reducing α-SMA-positive cells in the early post-operative period benefited nerve regeneration the most, resulting in more rapid restoration of nerve densities in all corneal layers of the ablation zone and of the corneal periphery.

To compare the temperatures of the ocular surface, eyelid, and periorbital skin in normal eyes with Sjögren's syndrome (SS) eyes, evaporative dry eyes (EDE), and aqueous deficient dry eyes (ADDE).10 eyes were analyzed in each age-matched group (normal, SS, EDE, and ADDE). A noninvasive infrared thermal camera captured two-dimensional images in three regions of interest (ROI) in each of three areas: the ocular surface, the upper eyelid, and the periorbital skin within a controlled environmental chamber. Mean temperatures in each ROI were calculated from the videos. Ocular surface time-segmented cooling rates were calculated over a 5-s blink interval.Relative to normal eyes, dry eyes had lower initial central OSTs (SS -0.71°C, EDE -0.55°C, ADDE -0.95°C, KW P.0001) and lower central upper lid temperatures (SS -0.24°C, ADDE -0.51°C, and EDE -0.54°C, KW P.0001). ADDE eyes had the lowest initial central OST (P.0001), while EDE eyes had the lowest central lid temperature and lower periorbital temperatures (P.0001). Over the 5-s interblink interval, the greatest rate of temperature loss occurred following eyelid opening, but varied by group (normals -0.52, SS -0.73, EDE -0.63, and ADDE -0.75°C/s). The ADDE group also had the most substantial heat loss over the 5-s interblink interval (-0.97°C).Differences in OST may be related to thermal differences in lids and periorbita along with an altered tear film. Thermography of the ocular surface, lids, and surrounding tissues may help to differentiate between different etiologies of dry eye.

In this study, we explore the usage of ocular surface temperature (OST) decay patterns to distinguished between dry eye patients with aqueous deficient dry eye (ADDE) and meibomian gland dysfunction (MGD). The OST profiles of 20 dry eye subjects were measured by a long-wave infrared thermal camera in a standardized environment (24 °C, and relative humidity (RH) 40%). The subjects were instructed to blink every 5 s after 20 ∼ 25 min acclimation. Exponential decay curves were fit to the average temperature within a region of the central cornea. We find the MGD subjects have both a higher initial temperature (p

To analyze the distribution of tear film osmolarity in patients with dry eye and its association with other ocular surface parameters.Tear osmolarity and other quantitative dry eye parameters were obtained from patients with 1) clinically significant dry eye (significant symptoms and ocular surface staining, n = 131), 2) symptoms-only dry eye (significant symptoms but no significant ocular surface staining, n = 52), and 3) controls (no significant symptoms or staining, n = 42).Tear osmolarity varied significantly across groups (P = 0.01), with patients with clinically significant dry eye having the highest tear osmolarity (312.0 ± 16.9 mOsm/L), control patients having the lowest tear osmolarity (305.6 ± 9.7 mOsm/L), and patients with symptoms-only dry eye falling in between (307.4 ± 5.6 mOsm/L). Patients with clinically significant dry eye also tended to have a greater intereye difference in osmolarity (12.0 ± 13.4) than did the individuals with symptoms-only dry eye (9.1 ± 12.4) and controls (9.0 ± 7.4) (P = 0.06). In multivariable regression models, higher tear osmolarity was associated with higher Ocular Surface Disease Index, discomfort subscore (P = 0.02), and higher corneal and conjunctival staining scores (P0.01 for both). Worse eye tear osmolarity was not correlated with the corresponding tear film breakup time or Schirmer test (P0.05 for both).Individuals with symptomatic dry eye that is not yet clinically significant seem to have higher and more variable osmolarity measurements than controls, potentially indicating that changes in osmolarity precede clinical findings.

Gabor-domain optical coherence microscopy (GDOCM) demonstrated in vivo corneal imaging with cellular resolution and differentiation in mice over a field of view of 1 mm2. Contact and non-contact imaging was conducted on six healthy and six hyperglycemic C57BL/6J mice. Cellular resolution in the 3D GDOCM images was achieved after motion correction. Corneal nerve fibers were traced and their lengths and branches calculated. Noncontact, label-free imaging of corneal nerves has clinical utility in health and disease, and in transplant evaluation. To the authors’ knowledge, this is the first report of in vivo 3D corneal imaging in mice with the capability to resolve nerve fibers using a non-contact imaging modality.

Purpose The aim was to assess the visual impact of ocular wavefront aberrations, corneal thickness, and corneal light scatter prospectively after performing a Descemet stripping automated endothelial keratoplasty (DSAEK) in humans. Methods Data were obtained prospectively from 20 eyes preoperatively and at 1, 3, 6, and 12 months post-DSAEK. At each visit, the best spectacle-corrected visual acuity and visual acuity with glare (brightness acuity testing) were recorded, and ocular wavefront measurements and corneal optical coherence tomography (OCT) were performed. The magnitude and the sign of individual Zernike terms [higher-order aberrations (HOAs)] were determined. Epithelial, host stromal, donor stromal, and total corneal thicknesses were quantified. The brightness and intensity profiles of OCT images were generated to quantify light scatter in the whole cornea, subepithelial region, anterior and posterior host stroma, interface, and donor stroma. Results The mean best spectacle-corrected visual acuity and glare disability at low light levels improved from 1 to 12 months post-DSAEK. All corneal thicknesses and ocular lower-order aberrations and HOAs were found to be stable from 1 to 12 months, whereas total corneal, host stromal, and interface brightness intensities decreased significantly over the same period. A repeated measures analysis of variance performed across the follow-up period revealed that the change in scatter, but not the change in the HOAs, could account for the variability occurring in the acuity from 1 to 12 months post-DSAEK. Conclusions Although ocular HOAs and scatter are both elevated over normal values post-DSAEK, our results demonstrate that the improvements in visual performance occurring over the first year post-DSAEK are associated with decreasing light scatter. In contrast, there were no significant changes in the ocular HOAs during this time. Because corneal light scatter decreased between 1 and 12 months despite there being stable corneal thicknesses over the same period, we conclude that factors that induced light scatter, other than tissue thickness or swelling (corneal edema), significantly impacted the visual improvements that occurred over time post-DSAEK. A better understanding of the cellular and extracellular matrix changes of the subepithelial region and interface, incurred by the surgical creation of a lamellar host-graft interface, and the subsequent healing of these tissues, is warranted.

A critical component of corneal scarring is the TGFβ-induced differentiation of corneal keratocytes into myofibroblasts. Inhibitors of this differentiation are potentially therapeutic for corneal scarring. In this study, we tested the relative effectiveness and mechanisms of action of two electrophilic peroxisome proliferator-activated receptor gamma (PPARγ) ligands: cyano-3,12-dioxolean-1,9-dien-28-oic acid-methyl ester (CDDO-Me) and 15-deoxy-Δ(-12,14)-prostaglandin J(2) (15d-PGJ(2)) for inhibiting TGFβ-induced myofibroblast differentiation in vitro. TGFβ was used to induce myofibroblast differentiation in cultured, primary human corneal fibroblasts. CDDO-Me and 15d-PGJ(2) were added to cultures to test their ability to inhibit this process. Myofibroblast differentiation was assessed by measuring the expression of myofibroblast-specific proteins (αSMA, collagen I, and fibronectin) and mRNA (αSMA and collagen III). The role of PPARγ in the inhibition of myofibroblast differentiation by these agents was tested in genetically and pharmacologically manipulated cells. Finally, we assayed the importance of electrophilicity in the actions of these agents on TGFβ-induced αSMA expression via Western blotting and immunofluorescence. Both electrophilic PPARγ ligands (CDDO-Me and 15d-PGJ(2)) potently inhibited TGFβ-induced myofibroblast differentiation, but PPARγ was only partially required for inhibition of myofibroblast differentiation by either agent. Electrophilic PPARγ ligands were able to inhibit myofibroblast differentiation more potently than non-electrophilic PPARγ ligands, suggesting an important role of electrophilicity in this process. CDDO-Me and 15d-PGJ(2) are strong inhibitors of TGFβ-induced corneal fibroblast to myofibroblast differentiation in vitro, suggesting this class of agents as potential novel therapies for corneal scarring warranting further study in pre-clinical animal models.

Background: Prospective interventional animal case series to investigate quantitatively changes in corneal light-scattering, corneal hysteresis, keratometry and pachymetry induced by circular Descemet's membrane incision. Methods: Thirty mature New Zealand White rabbits were divided into three study groups: (i) surgical intervention with circular Descemet's incision; (ii) surgical control; and (iii) medical control. Group 1 eyes had two paracenteses placed 120 degrees apart and an 8.5-mm-diameter Descemetorhexis was created with a reverse Sinskey hook. Group 2 eyes had two paracenteses placed 120 degrees apart. The main outcome measures were scatterometry, corneal hysteresis, pachymetry and keratometry measurements, which were performed prior to and 2 weeks following the interventions. Histology and transmission electron microscopy were performed post-mortem in representative eyes. Results: Eyes that had undergone circular Descemet's incision had significantly decreased mean keratometry (43.9 ± 0.7 dioptres [mean ± standard deviation] preoperatively vs. 43.5 ± 0.9 dioptres postoperatively, P = 0.007). Circular Descemet's membrane incision did not significantly change corneal hysteresis (4.4 ± 1.1 mmHg preoperatively vs. 4.6 ± 0.9 mmHg postoperatively, P = 0.664). Corneal light scattering decreased after Descemet's scoring (0.00254 ± 0.00059 preoperatively vs. 0.00206 ± 0.00031 postoperatively, P = 0.0025). Pachymetry measurements remained relatively stable (341.3 ± 18.6 µm preoperatively vs. 330.6 ± 20.0 µm postoperatively) without postoperative oedema. Conclusions: Circular Descemet's scoring flattened the corneal curvature by a mean of 0.4 dioptres without affecting corneal hysteresis in rabbit corneas. These findings may have important implications for ongoing developments in endothelial keratoplasty.

In biophotonics imaging, one important and quantitative task is layer-thickness estimation. In this study, we investigate the approach of combining optical coherence tomography and a maximum-likelihood (ML) estimator for layer thickness estimation in the context of tear film imaging. The motivation of this study is to extend our understanding of tear film dynamics, which is the prerequisite to advance the management of Dry Eye Disease, through the simultaneous estimation of the thickness of the tear film lipid and aqueous layers. The estimator takes into account the different statistical processes associated with the imaging chain. We theoretically investigated the impact of key system parameters, such as the axial point spread functions (PSF) and various sources of noise on measurement uncertainty. Simulations show that an OCT system with a 1 μm axial PSF (FWHM) allows unbiased estimates down to nanometers with nanometer precision. In implementation, we built a customized Fourier domain OCT system that operates in the 600 to 1000 nm spectral window and achieves 0.93 micron axial PSF in corneal epithelium. We then validated the theoretical framework with physical phantoms made of custom optical coatings, with layer thicknesses from tens of nanometers to microns. Results demonstrate unbiased nanometer-class thickness estimates in three different physical phantoms.

Kyle MacLean,1 Holly B Hindman2,3 1University of Rochester School ofMedicine and Dentistry, Rochester, NY, USA; 2The Flaum Eye Institute, University of Rochester, Rochester, NY, USA; 3Center for Visual Science, University of Rochester, Rochester, NY, USA Purpose: To assess medical student ophthalmic educational exposure and service provided through the University of Rochester’s UR Well Eye Care (URWEC) program, a student-run initiative in which medical students provide supervised eye care to an uninsured urban population.Design: Retrospective chart review.Subjects: Consecutive patients seen at the student-run URWEC in Rochester, NY, USA between June 2008 and June 2013.Methods: One hundred and forty-five of 148 charts of consecutive patients seen at URWEC over the 5-year period were identified and reviewed. Data on patient demographics, reason for visit, history, examination, diagnoses, and management were collected into a database. Main outcome measures: Main outcome measures included reasons for referral, student performance of ophthalmic examination components, ophthalmic diagnoses, and hours of volunteer service rendered. Results: Patients came from a variety of countries and educational and racial backgrounds. The most common reason for referral to URWEC was diabetic screening eye exams (66/145, 46%). Student volunteers performed the following examination components in 79%–100% of visits under direct supervision of an attending ophthalmologist: visual acuity, pupils, extraocular movements, confrontation visual fields, intraocular pressure, drop administration, slit-lamp examination, and dilated fundoscopic exam. The most common diagnosis other than refractive error was cataract (29/145, 20%). Almost half of patients (66/145, 46%) were diagnosed with potentially vision-threatening conditions. Six hundred and thirty hours of community service were rendered by students and attending ophthalmologists during the 5-year period.Conclusion: Student-run eye clinics provide a longitudinal setting where students can receive one-on-one training with attending ophthalmologists, attain a broad clinical exposure, and provide a needed service in their communities. Keywords: medical student education, student-run clinic, student-run eye clinic, volunteer eye clinic, ophthalmology education

To demonstrate the effect of apraclonidine on anisocoria and ptosis in Horner syndrome, one drop of 0.5% apraclonidine was instilled in both eyes of 3 patients who presented with acute Horner syndrome, and the effect on ptosis and anisocoria was documented. As reported in the literature, one drop of 0.5% apraclonidine reverses the anisocoria of Horner syndrome. In addition, 0.5% apraclonidine leads to a complete resolution of the ptosis associated with Horner syndrome, a finding reported once in the literature. Apraclonidine is a safe and readily available alternative to cocaine for the diagnosis of Horner syndrome.

Dry eye syndrome is a disease of the ocular surface and tear film that is prevalent in older adults. Even though the degree of visual acuity loss in dry eye patients is commonly mild-to-moderate, in the aging population, this minimal change in visual status can lead to a significant decrease in visual function and quality of life. A healthy ocular surface is maintained by appropriate tear production and tear drainage, and deficiencies in this delicate balance can lead to dryness. In the aging eye, risk factors such as polypharmacy, androgen deficiency, decreased blink rates, and oxidative stress can predispose the patient to developing dry eye that is frequently more severe, has higher economic costs, and leads to worse consequences to the well-being of the patient. Understanding why elderly patients are at higher risk for developing dry eyes can provide insights into the diagnosis and management of the growing number of older adults struggling with dry eye and minimize the burden of disease on our aging population.

Corneal scarring remains a major cause of blindness world-wide, with limited treatment options, all of which have side-effects. Here, we tested the hypothesis that topical application of Rosiglitazone, a Thiazolidinedione and ligand of peroxisome proliferator activated receptor gamma (PPARγ), can effectively block scar formation in a cat model of corneal damage. Adult cats underwent bilateral epithelial debridement followed by excimer laser ablation of the central corneal stroma to a depth of ~160 µm as a means of experimentally inducing a reproducible wound. Eyes were then left untreated, or received 50 µl of either 10 µM Rosiglitazone in DMSO/Celluvisc, DMSO/Celluvisc vehicle or Celluvisc vehicle twice daily for 2 weeks. Cellular aspects of corneal wound healing were evaluated with in vivo confocal imaging and post-mortem immunohistochemistry for alpha smooth muscle actin (αSMA). Impacts of the wound and treatments on optical quality were assessed using wavefront sensing and optical coherence tomography at 2, 4, 8 and 12 weeks post-operatively. In parallel, cat corneal fibroblasts were cultured to assess the effects of Rosiglitazone on TGFβ-induced αSMA expression. Topical application of Rosiglitazone to cat eyes after injury decreased αSMA expression and haze, as well as the induction of lower-order and residual, higher-order wavefront aberrations compared to vehicle-treated eyes. Rosiglitazone also inhibited TGFβ-induced αSMA expression in cultured corneal fibroblasts. In conclusion, Rosiglitazone effectively controlled corneal fibrosis in vivo and in vitro, while restoring corneal thickness and optics. Its topical application may represent an effective, new avenue for the prevention of corneal scarring with distinct advantages for pathologically thin corneas.

Prospective interventional animal case series to investigate quantitatively changes in corneal light-scattering, corneal hysteresis, keratometry and pachymetry induced by circular Descemet's membrane incision. Thirty mature New Zealand White rabbits were divided into three study groups: (i) surgical intervention with circular Descemet's incision; (ii) surgical control; and (iii) medical control. Group 1 eyes had two paracenteses placed 120 degrees apart and an 8.5-mm-diameter Descemetorhexis was created with a reverse Sinskey hook. Group 2 eyes had two paracenteses placed 120 degrees apart. The main outcome measures were scatterometry, corneal hysteresis, pachymetry and keratometry measurements, which were performed prior to and 2 weeks following the interventions. Histology and transmission electron microscopy were performed post-mortem in representative eyes. Eyes that had undergone circular Descemet's incision had significantly decreased mean keratometry (43.9 ± 0.7 dioptres [mean ± standard deviation] preoperatively vs. 43.5 ± 0.9 dioptres postoperatively, P = 0.007). Circular Descemet's membrane incision did not significantly change corneal hysteresis (4.4 ± 1.1 mmHg preoperatively vs. 4.6 ± 0.9 mmHg postoperatively, P = 0.664). Corneal light scattering decreased after Descemet's scoring (0.00254 ± 0.00059 preoperatively vs. 0.00206 ± 0.00031 postoperatively, P = 0.0025). Pachymetry measurements remained relatively stable (341.3 ± 18.6 µm preoperatively vs. 330.6 ± 20.0 µm postoperatively) without postoperative oedema. Circular Descemet's scoring flattened the corneal curvature by a mean of 0.4 dioptres without affecting corneal hysteresis in rabbit corneas. These findings may have important implications for ongoing developments in endothelial keratoplasty.

Endocapsular intraocular lens (IOL) dislocation can be a challenge for the anterior segment surgeon. We describe a novel surgical strategy for repositioning an anteriorly dislocated endocapsular IOL by suturing it to the ciliary sulcus using an anterior segment approach in a patient with retinitis pigmentosa (RP).

A 55-year-old woman presented to the emergency room with complete loss of vision in the left eye after being bit in the face by her autistic grandson. She had a small upper eyelid laceration and an anophthalmic socket on the left side. A thorough history revealed that the bite had caused traumatic luxation of her globe, which had allowed the child to transect the optic nerve with his teeth. Careful attention was directed toward the prevention of retrograde infection in this unusual case of traumatic enucleation.

Objective To determine if postsurgical corneal interface abnormalities after deep lamellar endothelial keratoplasty (DLEK) cause increased light scattering or wavefront aberrations that may help to explain decreased best-corrected visual acuity in DLEK patients compared with penetrating keratoplasty (PK) patients. Design Prospective comparative case series. Participants Clinically clear corneas of 4 eyes that had undergone DLEK surgery and 4 eyes that had PK were studied. Normal control data for light scattering was collected from 12 right eyes and 11 left eyes with normal corneas. Methods Corneal light scattering was measured with a scatterometer designed at the Johns Hopkins Applied Physics Laboratory, and wavefront analysis was performed using standard methods with a Hartmann-Shack wavefront sensor. Main Outcome Measures Corneal scattering measurements were normalized by taking the ratio of the subject's corneal light scattering to a reference material. A scattering index was calculated as the ratio of the normalized scattering for a given patient's cornea to the average scattering of normal corneas. Astigmatism and higher-order aberrations were analyzed using standard data output from wavefront analysis and Zernike polynomial decomposition. Results The mean scattering index was significantly higher after DLEK (1.78±0.29, mean±standard deviation [SD]) than after PK (1.03±0.27; P = 0.043). The higher-order root mean square (RMS) wavefront error was significantly higher after PK (0.71±0.11 μm, mean±SD) than after DLEK (0.44±0.12 μm; P = 0.029). Zernike polynomial decomposition of the wavefront aberrations revealed that regular corneal astigmatism was the most important aberration component for both PK and DLEK, but the PK patients had significantly more regular astigmatism (1.7±0.45 diopters [D], mean±SD) than did the DLEK patients (0.84±0.27 D; P = 0.029). Conclusions Our data quantitatively support subclinical corneal haze as an explanation for the limited visual acuity after DLEK as compared with PK. Intraoperative or postoperative modifications to reduce stromal haze after DLEK may result in better visual acuity outcomes.

To extend our understanding of tear film dynamics for the management of dry eye disease, we propose a method to optically sense the tear film and estimate simultaneously the thicknesses of the lipid and aqueous layers. The proposed method, SDT-OCT, combines ultra-high axial resolution optical coherence tomography (OCT) and a robust estimator based on statistical decision theory (SDT) to achieve thickness measurements at the nanometer scale. Unlike conventional Fourier-domain OCT where peak detection of layers occurs in Fourier space, in SDT-OCT thickness is estimated using statistical decision theory directly on the raw spectra acquired with the OCT system. In this paper, we demonstrate in simulation that a customized OCT system tailored to ~1 µm axial point spread function (FWHM) in the corneal tissue, combined with the maximum-likelihood estimator, can estimate thicknesses of the nanometer-scale lipid and micron-scale aqueous layers of the tear film, simultaneously, with nanometer precision. This capability was validated in experiments using a physical phantom that consists of two layers of optical coatings that mimic the lipid and aqueous layers of the tear film.

To investigate the contribution ocular aberrations have on visual performance by quantifying improvements in best-corrected visual acuity (VA) and contrast sensitivity (CS) obtained with higher-order aberration (HOA) correction after penetrating (PK), deep anterior lamellar (DALK), or Descemet's stripping automated endothelial keratoplasty (DSAEK).Sixteen eyes were evaluated from 14 subjects who underwent PK (n = 5), DALK (n = 6), or DSAEK (n = 5) greater than 1 year prior to study enrollment. Ocular aberrations were measured and an adaptive optics system was used to correct ocular lower-order aberration (LOA) and HOA. VA and CS were measured for each subject with LOA or full-aberration correction. CS was measured at each of three spatial frequencies: 4, 8, and 12 cycles/deg.All keratoplasty groups had more aberration than that of a normal myopic population and experienced significant VA gains with full-aberration correction (P0.0013). PK subjects had better VA than that of DSAEK subjects with LOA correction (logMAR VA 0.03 ± 0.05 vs. 0.25 ± 0.05; P = 0.0870). After HOA correction this trend persisted (P = 0.1734). DSAEK subjects also experienced less VA benefit from full-aberration correction than that of PK and DALK subjects. All keratoplasty groups demonstrated similar CS benefits from full-aberration correction despite differing higher-order root-mean-square magnitudes.PK eyes had better logMAR VA than that of DSAEK eyes with LOA correction, whereas DALK eyes performed intermediate between the two. When full correction was applied, the same trend persisted. The findings suggest that factors other than aberration contribute to decrements in VA with DSAEK compared with PK.

Keratocytes are the main cellular component of the stroma. They display a dendritic morphology and have gap junctions at the end of their processes that allow for rapid intercellular communication.1 By generating and maintaining the structure of the collagen lamellae and the stromal extracellular matrix, keratocytes play an important role in maintaining corneal clarity.2 In healthy corneas, keratocytes are believed to regulate stromal balance by synthesizing new collagens and proteoglycans and secreting enzymes to degrade old or unhealthy stroma.3 In response to wounding (e.g., during penetrating keratoplasty, laser refractive surgery, and accidental corneal insult), keratocytes become activated and can transform into repair phenotypes that include corneal fibroblasts and myofibroblasts. Expression of the cell surface protein Thy-1 indicates keratocyte transformation into corneal fibroblasts.4 Myofibroblasts are further characterized by their expression of α-smooth muscle actin (α-SMA), which provides them with contractile ability. Using electron microscopy and fluorescent probes for microfilaments, such corneal fibroblasts can be identified adjacent to wounds.5 Wound contraction correlates with intracellular F-actin expression in activated cells and with the synthesis and extracellular deposition of fibronectin and collagen type I. These intracellular and extracellular components are aligned and linked by α5β1, an integrin expressed by activated cells. The contraction of actin filaments causes a tightening of the interconnected network of cells and extracellular matrix.6 The expression of α-SMA, a biochemical marker for myofibroblast transformation, is exclusively localized within wounds and associates temporally with their contraction.7 TGF-β induces α-SMA expression and myofibroblast transformation in cultured corneal keratocytes, and antibodies to TGF-β reduce corneal fibrosis and fibronectin deposition in vivo.8–10 Increasing data suggest that not all fibroblasts behave in the same manner. There is heterogeneity in fibroblast phenotypic response to TGF-β, depending on the tissue of origin.11 These phenotypic differences may be the result of different signal transduction cascades that are elicited in response to TGF-β stimulation in different tissue types.11 However, phenotypic heterogeneity has also been observed in cells derived from the same tissue, and differences in the response to TGF-β have been correlated with certain cell surface markers. For example, orbital fibroblasts that are Thy-1 positive differentiate into myofibroblasts, whereas Thy-1–negative orbital fibroblasts differentiate into lipofibroblasts.12 There can also be heterogeneity in the proliferation rates of fibroblasts, depending on whether the cells are derived from quiescent or fibrotic tissue from the same source.13 Heterogeneity in the phenotypic response of fibroblasts to different growth factors has also been identified.14 Generally, though differences tend to be more remarkable when comparing cells derived from different tissues, they can also occur for cells derived from the same tissue. Although there is a growing body of knowledge regarding how keratocytes respond to injury, no systematic investigation of corneal keratocyte heterogeneity has been conducted based on corneal location (i.e., anterior vs. posterior, central vs peripheral cornea). Yet, normal, healthy corneas show clear differences between the anterior and posterior stroma in vivo. The anterior stroma has a greater density of keratocytes than the posterior stroma.15 Keratocytes in the anterior stroma are smaller than those in the posterior stroma.15 The anterior stroma also has smaller diameter collagen fibrils than the posterior stroma,16 and there are differences in glucose concentrations and proteoglycan ratios between the anterior and posterior stroma, with the anterior stroma having a lower concentration of glucose and a higher ratio of dermatan sulfate to keratan sulfate.17,18 The difference in the proteoglycan distribution likely affects stromal hydration; the anterior stroma has a lower water content than the posterior stroma.17 It may also impact optical properties across the stroma. For example, the anterior stroma has been found to have a higher refractive index than the posterior stroma,19 and differential corneal swelling20 in the stroma has been shown to affect corneal light scatter21 and transparency.22 Although structural differences between anterior and posterior stroma have been well characterized in situ, there is a dearth of information on how anterior and posterior keratocytes respond to injury and wounding stimuli. This knowledge has pertinent clinical applications as corneal surgeons increasingly turn toward lamellar and endothelial keratoplasties. These procedures entail differential surgical manipulation and wounding of the anterior and posterior corneal stroma. Given that corneal keratocyte activation and transformation into scar-forming myofibroblasts ultimately impacts postoperative ocular optics and visual performance, understanding differences between the anterior and posterior keratocytic response to wounding stimuli may be critical to patient outcomes. In this study, we asked whether feline cultured anterior and posterior primary keratocytes differ in their entry into the cell cycle, activation, and transformation into myofibroblasts in response to TGF-β1 stimulation and whether these differences translate into differences in wound closure in vitro. The feline cornea was selected for the present set of experiments because its curvature, size, thickness, and histologic and optical properties are more similar to those of humans than other mammals.23 For this reason, cats have been used extensively to study incisional and laser-induced corneal wound healing and its optical and biomechanical correlates.6,10,24–28 Feline and human corneas behave similarly after injury; thus, the cat cornea is considered a good model for understanding penetrating and posterior lamellar keratoplasties in humans.29–31