Impact of topical anti-fibrotics on corneal nerve regeneration in vivo.

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 ßIII-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.

Effects of Prolonged Reading on Dry Eye.

PURPOSE: To demonstrate the effects of prolonged silent reading on tear film and ocular surface parameters. DESIGN: Prospective, observational clinical study. PARTICIPANTS: A total of 177 patients with dry eye and 34 normal controls aged 50 years and older. METHODS: 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. MAIN OUTCOME MEASURES: Changes in tear film and ocular surface parameters after reading. RESULTS: 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 (P < 0.001) and for corneal staining in the control group (P < 0.01). At baseline, OSDI scores correlated only with corneal and conjunctival staining scores (r = 0.19, P = 0.006 and r = 0.27, P < 0.001). 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, P < 0.001 and r = 0.22, P = 0.001). Changes in TBUT and Schirmer's test correlated significantly with their respective baseline values (r = -0.61, P < 0.001 and r = -0.44, P < 0.001), 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). CONCLUSIONS: 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.

In vivo thickness dynamics measurement of tear film lipid and aqueous layers with optical coherence tomography and maximum-likelihood estimation.

Dry eye disease (DED) is a common ophthalmic condition that is characterized by tear film instability and leads to ocular surface discomfort and visual disturbance. Advancements in the understanding and management of this condition have been limited by our ability to study the tear film secondary to its thin structure and dynamic nature. Here, we report a technique to simultaneously estimate the thickness of both the lipid and aqueous layers of the tear film in vivo using optical coherence tomography and maximum-likelihood estimation. After a blink, the lipid layer was rapidly thickened at an average rate of 10 nm/s over the first 2.5 s before stabilizing, whereas the aqueous layer continued thinning at an average rate of 0.29 µm/s of the 10 s blink cycle. Further development of this tear film imaging technique may allow for the elucidation of events that trigger tear film instability in DED.

Inhibitory effects of PPARγ ligands on TGF-ß1-induced corneal myofibroblast transformation.

Corneal scarring, whether caused by trauma, laser refractive surgery, or infection, remains a significant problem for humans. Certain ligands for peroxisome proliferator-activated receptor gamma (PPARγ) have shown promise as antiscarring agents in a variety of body tissues. In the cornea, their relative effectiveness and mechanisms of action are still poorly understood. Here, we contrasted the antifibrotic effects of three different PPARγ ligands (15-deoxy-Δ12,14-prostaglandin J2, troglitazone, and rosiglitazone) in cat corneal fibroblasts. Western blot analyses revealed that all three compounds reduced transforming growth factor (TGF)-ß1-driven myofibroblast differentiation and up-regulation of α-smooth muscle actin, type I collagen, and fibronectin expression. Because these effects were independent of PPARγ, we ascertained whether they occurred by altering phosphorylation of Smads 2/3, p38 mitogen-activated protein kinase, stress-activated protein kinase, protein kinase B, extracellular signal-regulated kinase, and/or myosin light chain 2. Only p38 mitogen-activated protein kinase phosphorylation was significantly inhibited by all three PPARγ ligands. Finally, we tested the antifibrotic potential of troglitazone in a cat model of photorefractive keratectomy-induced corneal injury. Topical application of troglitazone significantly reduced α-smooth muscle actin expression and haze in the stromal ablation zone. Thus, the PPARγ ligands tested here showed great promise as antifibrotics, both in vitro and in vivo. Our results also provided new evidence for the signaling pathways that may underlie these antifibrotic actions in corneal fibroblasts.

Assessing microstructures of the cornea with Gabor-domain optical coherence microscopy: pathway for corneal physiology and diseases.

Gabor-domain optical coherence microscopy (GD-OCM) was applied ex vivo in the investigation of corneal cells and their surrounding microstructures with particular attention to the corneal endothelium. Experiments using fresh pig eyeballs, excised human corneal buttons from patients with Fuchs' endothelial dystrophy (FED), and healthy donor corneas were conducted. Results show in a large field of view (1 mm×1 mm) high definition images of the different cell types and their surrounding microstructures through the full corneal thickness at both the central and peripheral locations of porcine corneas. Particularly, an image of the endothelial cells lining the bottom of the cornea is highlighted. As compared to healthy human corneas, the corneas of individuals with FED show characteristic microstructural alterations of the Descemet's membrane and increased size and number of keratocytes. The GD-OCM-based imaging system developed may constitute a novel tool for corneal imaging and disease diagnosis. Also, importantly, it may provide insights into the mechanism of corneal physiology and pathology, particularly in diseases of the corneal endothelium.

Thermal analysis of dry eye subjects and the thermal impulse perturbation model of ocular surface.

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 âˆ¼ 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 < 0.022) and a higher asymptotic temperature (p < 0.007) than the ADDE subjects. We hypothesize the temperature difference among the subpopulations is due to tear volume and heat transfer mechanisms. To study the validity of our claim, we develop a mathematical model, referred to as the thermal impulse perturbation (TIP) model. We conclude that long-wave-infrared thermal imaging is a plausible tool in assisting with the classification of dry eye patient.

Evaluation of the effects of circular Descemet's membrane incision on the biomechanical, topographic and optical properties of rabbit corneas.

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.

Unbiased corneal tissue analysis using Gabor-domain optical coherence microscopy and machine learning for automatic segmentation of corneal endothelial cells.

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 < 0.001) with the manual segmentation on the same images, and correlation of 0.91 (p < 0.001) with the corresponding manually counted SM results. CONCLUSIONS: Automated endothelial cell counting on GDOCM images with large field of view eliminates selection bias and reduces sampling error, which both affect the gold standard of manual counting on SM images.

In vivo imaging of corneal nerves and cellular structures in mice with Gabor-domain optical coherence microscopy.

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.

Sudden Death in a Child With Ocular Lesions.

This case report describes a patient treated for ocular lesions who died suddenly at age 8 years and was diagnosed postmortem with Carney complex.

Capabilities of Gabor-domain optical coherence microscopy for the assessment of corneal disease.

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.

Corneal myofibroblasts inhibit regenerating nerves during wound healing.

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-ß1) 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-ß 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.

Evaluation of deep lamellar endothelial keratoplasty surgery using scatterometry and wavefront analyses.

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 microm, mean+/-SD) than after DLEK (0.44+/-0.12 microm; 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.

Tear Osmolarity and Correlation With Ocular Surface Parameters in Patients With Dry Eye.

PURPOSE: To analyze the distribution of tear film osmolarity in patients with dry eye and its association with other ocular surface parameters. METHODS: 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). RESULTS: 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 (P < 0.01 for both). Worse eye tear osmolarity was not correlated with the corresponding tear film breakup time or Schirmer test (P > 0.05 for both). CONCLUSIONS: 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.

Ochrobactrum anthropi Keratitis with Focal Descemet's Membrane Detachment and Intracorneal Hypopyon.

Purpose. To describe a unique case of O. anthropi keratitis associated with a rare manifestation of Descemet's membrane detachment and intracorneal hypopyon and to discuss challenges in diagnosis and management. Methods. Best-corrected visual acuity was measured with Snellen letters. Corneal scrapings were performed and aerobic, viral, herpetic, acid-fast bacilli, Acanthamoeba, and fungal stains and cultures were obtained. Following evisceration, tissue was evaluated for histologic features and again stained for bacteria, mycobacteria, Acanthamoeba, fungi, and viral particles. Results. Initial presentation to our institute was notable for a corneal ulcer, focal Descemet's membrane detachment, and intracorneal hypopyon. Speciation of initial corneal scrapes revealed Ochrobactrum anthropi and initial management included fortified tobramycin. Despite medical therapy, the patient developed a corneal perforation and required subsequent evisceration. Conclusion. O. anthropi is an emerging ocular pathogen that has not been previously reported in cases of keratitis. As this pathogen becomes increasingly recognized as a source of ocular infections, it is important to identify and treat aggressively to avoid vision-threatening disease.

Temperatures of the Ocular Surface, Lid, and Periorbital Regions of Sjögren's, Evaporative, and Aqueous-Deficient Dry Eyes Relative to Normals.

PURPOSE: 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). METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

The Diagnostic and Therapeutic Challenges of Posttraumatic Iris Implantation Cysts: Illustrative Case Presentations and a Review of the Literature.

Posttraumatic iris implantation cysts are rare ocular findings that are often associated with poor visual outcomes. Iris implantation cysts can present clinicians with diagnostic and therapeutic challenges given their variable presentations and frequently destructive nature. In this paper, we provide descriptions of two unusual cases of posttraumatic iris implantation cysts. The first case is of a recurrent keratin-filled iris implantation cyst that developed after open globe injury and intraocular implantation of cilia and was treated with cyst debulking procedures, injections of 5-Fluorouracil, and iridocyclectomy. The second case is of recurrent posttraumatic serous iris implantation cysts that were treated with laser, cyst aspiration, and injections of 5-Fluorouracil. We use these cases as a platform to discuss the different manifestations of implantation cysts, the roles of anterior segment optical coherence tomography, ultrasound biomicroscopy, and histopathology in facilitating timely and accurate diagnosis and review the range of available therapeutic modalities. We discuss conservative treatment approaches, including the novel use of 5-Fluorouracil therapy as an adjunct therapy, as well as more aggressive surgical excision requiring ocular reconstruction. Through a discussion of these cases and review of the literature, we provide recommendations to assist clinicians in managing this uncommon but vision-threatening condition and minimizing complications.

Aging: a predisposition to dry eyes.

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.

UR Well Eye Care: a model for medical student ophthalmology education and service in the community.

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.

Recurrent nontuberculous mycobacterial endophthalmitis: a diagnostic conundrum.

OBJECTIVE: To report a case of recurrent nontuberculous mycobacterial endophthalmitis in the context of neurotrophic keratopathy secondary to herpes zoster ophthalmicus that had an atypical presentation and complex course, and highlights the challenges of causative organism identification and therapeutic interventions in this condition. METHODS: A retrospective chart review was conducted to determine the visual outcomes of the patient. RESULTS: A 68-year-old pseudophakic male with long-standing neurotrophic keratopathy and perforated descemetocele managed with cyanoacrylate glue and a contact bandage lens in the left eye, began experiencing recurrent episodes of endophthalmitis after undergoing a penetrating keratoplasty. Several therapeutic procedures including an anterior chamber washout, two pars plana vitrectomies, explantation of the posterior chamber intraocular lens and capsular bag, and multiple intravitreal antimicrobial injections, were performed to which he has ultimately responded favorably, with no signs of infection to date and stable visual acuity. The causative organism of his recurrent infections was initially identified as Mycobacterium abscessus through biochemical testing and 16S ribosomal ribonucleic acid gene sequencing; however, repeat polymerase chain reaction (PCR) and sequencing of the 65 kDa heat shock protein (hsp65) gene for experimental purposes confirmed the accurate identification of the organism to be Mycobacterium chelonae. Given the greater reliability of PCR and sequencing of the hsp65 gene over traditional biochemical tests and culture techniques, M. chelonae was likely the infectious agent all along, and the organism was originally misidentified on the basis of less accurate tests. CONCLUSION: Recurrent atypical mycobacterial endophthalmitis requires expedient identification and management to prevent poor visual outcomes. Standard biochemical testing can identify the causative organism but is limited by the inability to distinguish between nontuberculous species reliably. We recommend the use of PCR in conjunction with sequencing of the hsp65 gene for reliable differentiation of M. chelonae and M. abscessus in atypical mycobacterial ocular infections. Minimum inhibitory concentration antibiotic susceptibility tests on cultured strains are the best guide to antibiotic selection, given the rapidly rising resistance to antimicrobials in atypical mycobacterial species.