Dysfunctional tear syndrome: dry eye disease and associated tear film disorders - new strategies for diagnosis and treatment.

Dysfunctional tear syndrome (DTS) is a common and complex condition affecting the ocular surface. The health and normal functioning of the ocular surface is dependent on a stable and sufficient tear film. Clinician awareness of conditions affecting the ocular surface has increased in recent years because of expanded research and the publication of diagnosis and treatment guidelines pertaining to disorders resulting in DTS, including the Delphi panel treatment recommendations for DTS (2006), the International Dry Eye Workshop (DEWS) (2007), the Meibomian Gland Dysfunction (MGD) Workshop (2011), and the updated Preferred Practice Pattern guidelines from the American Academy of Ophthalmology pertaining to dry eye and blepharitis (2013). Since the publication of the existing guidelines, new diagnostic techniques and treatment options that provide an opportunity for better management of patients have become available. Clinicians are now able to access a wealth of information that can help them obtain a differential diagnosis and treatment approach for patients presenting with DTS. This review provides a practical and directed approach to the diagnosis and treatment of patients with DTS, emphasizing treatment that is tailored to the specific disease subtype as well as the severity of the condition.

Optical coherence contrast imaging using gold nanorods in living mice eyes.

BACKGROUND: Optical coherence tomography (OCT) is a powerful imaging modality to visualize tissue structures, with axial image pixel resolution as high as 1.6 µm in tissue. However, OCT is intrinsically limited to providing structural information as the OCT contrast is produced by optically scattering tissues. METHODS: Gold nanorods (GNRs) were injected into the anterior chamber (AC) and cornea of mice eyes which could create a significant OCT signal and hence could be used as a contrast agent for in vivo OCT imaging. RESULTS: A dose of 30 nM of GNRs (13 nm in diameter and 45 nm in length) were injected to the AC of mice eyes and produced an OCT contrast nearly 50-fold higher than control mice injected with saline. Furthermore, the lowest detectable concentration of GNRs in living mice AC was experimentally estimated to be as low as 120 pM. CONCLUSIONS: The high sensitivity and low toxicity of GNRs brings great promise for OCT to uniquely become a high-resolution molecular imaging modality.

Molecular histopathology using gold nanorods and optical coherence tomography.

PURPOSE: To examine the novel application of a commercially available optical coherence tomography (OCT) system toward molecular histopathology using gold nanorod (GNR) linked antibodies as a functionalized contrast agent to evaluate ocular surface squamous neoplasia (OSSN). METHODS: GNRs were synthesized and covalently attached to anti-glucose transporter-1 (GLUT-1) antibodies via carbodiimide chemistry. Three specimens from each of three distinct categories of human conjunctival tissue were selected for analysis, including conjunctiva without epithelial atypia (controls); conjunctival intraepithelial neoplasia, carcinoma in situ (CIS); and conjunctival squamous cell carcinoma (SCC). Tissue sections were incubated initially with GNR tagged anti-GLUT-1 antibodies and then with a fluorescent-tagged secondary antibody. Immunofluorescence and OCT imaging of the tissue was performed and the results were correlated to the light microscopic findings on traditional hemotoxyin and eosin stained sections. RESULTS: No binding of the functionalized GNRs was observed within the epithelium of three normal conjunctiva controls. While immunofluorescence disclosed variable binding of the functionalized GNRs to atypical epithelial cells in all six cases of OSSN, the enhancement of the OCT signal in three cases of CIS was insufficient to distinguish these specimens from normal controls. In two of three cases of SCC, binding of functionalized GNRs was sufficient to produce an increased scattering effect on OCT in areas correlating to atypical epithelial cells which stained intensely on immunofluorescence imaging. Binding of functionalized GNRs was sufficient to produce an increased scattering effect on OCT in areas correlating to regions of erythrocytes and hemorrhage which stained intensely on immunofluorescence imaging within all nine tested samples. CONCLUSIONS: We have demonstrated the use of OCT for molecular histopathology using functionalized gold nanorods in the setting of OSSN. Our results suggest a threshold concentration of functionalized GNRs within tissue is required to achieve a detectable enhancement in scattering of the OCT signal.

Single step nanoplasmonic immunoassay for the measurement of protein biomarkers.

A nanoplasmonic biosensor for highly-sensitive, single-step detection of protein biomarkers is presented. The principle is based on the utilization of the optical scattering properties of gold nanorods (GNRs) conjugated to bio-recognition molecules. The nanoplasmonic properties of the GNRs were utilized to detect proteins using near-infrared light interferometry. We show that the antibody-conjugated GNRs can specifically bind to our model analyte, Glucose Transporter-1 (Glut-1). The signal intensity of back-scattered light from the GNRs bound after incubation, correlated well to the Glut-1 concentration as per the calibration curve. The detection range using this nanoplasmonic immunoassay ranges from 10 ng/mL to 1 ug/mL for Glut-1. The minimal detectable concentration based on the lowest discernable concentration from zero is 10 ng/mL. This nanoplasmonic immunoassay can act as a simple, selective, sensitive strategy for effective disease diagnosis. It offers advantages such as wide detection range, increased speed of analysis (due to fewer incubation/washing steps), and no label development as compared to traditional immunoassay techniques. Our future goal is to incorporate this detection strategy onto a microfluidic platform to be used as a point-of-care diagnostic tool.

Visual outcomes in pediatric optic pathway glioma after conformal radiation therapy.

PURPOSE: To assess visual outcome prospectively after conformal radiation therapy (CRT) in children with optic pathway glioma. METHODS AND MATERIALS: We used CRT to treat optic pathway glioma in 20 children (median age 9.3 years) between July 1997 and January 2002. We assessed changes in visual acuity using the logarithm of the minimal angle of resolution after CRT (54 Gy) with a median follow-up of 24 months. We included in the study children who underwent chemotherapy (8 patients) or resection (9 patients) before CRT. RESULTS: Surgery played a major role in determining baseline (pre-CRT) visual acuity (better eye: P=.0431; worse eye: P=.0032). The visual acuity in the worse eye was diminished at baseline (borderline significant) with administration of chemotherapy before CRT (P=.0726) and progression of disease prior to receiving CRT (P=.0220). In the worse eye, improvement in visual acuity was observed in patients who did not receive chemotherapy before CRT (P=.0289). CONCLUSIONS: Children with optic pathway glioma initially treated with chemotherapy prior to receiving radiation therapy have decreased visual acuity compared with those who receive primary radiation therapy. Limited surgery before radiation therapy may have a role in preserving visual acuity.

Phototherapeutic keratectomy for the treatment of subepithelial fibrosis and anterior corneal scarring after descemet stripping automated endothelial keratoplasty.

PURPOSE: To describe the use of phototherapeutic keratectomy (PTK) and transepithelial photorefractive keratectomy (PRK) for the treatment of subepithelial fibrosis and anterior corneal scarring after Descemet stripping automated endothelial keratoplasty (DSAEK). METHODS: The settings included the Department of Ophthalmology, Bascom Palmer Eye Institute, Miami, FL, and Carolina Cataract and Laser Center, Ladson, SC. Two patients with Fuchs endothelial dystrophy were noted to have anterior corneal opacities and corneal decompensation before DSAEK. Although both patients demonstrated improvement in corneal edema after DSAEK, they were left with residual anterior corneal opacities that were visually significant. The opacities were treated with excimer laser photoablation. RESULTS: Both patients demonstrated an improvement in best-corrected visual acuity after elimination of the anterior corneal opacity using PTK or transepithelial PRK. CONCLUSIONS: Excimer laser ablation is an effective option for the treatment of residual subepithelial fibrosis and anterior corneal scarring after DSAEK. When appropriate, use of PTK or PRK can also eliminate residual refractive error.

Vision-related quality of life in persons with unilateral branch retinal vein occlusion using the 25-item National Eye Institute Visual Function Questionnaire.

AIM: To evaluate vision-related quality of life in persons with branch retinal vein occlusion (BRVO) using the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25). DESIGN: Observational, cross-sectional, interviewer-administered study. METHODS: 46 patients with unilateral BRVO were included in this study. Scores on the VFQ-25 were analysed and converted to scaled scores per NEI VFQ-25 algorithms. Clinical data including age, gender, employment status, living arrangements, visual acuity, number of systemic diseases and duration of BRVO were also recorded. Subscale results were compared with previously published data, and subgroup analyses were performed. RESULTS: Mean adjusted subscale responses among BRVO patients were higher (except for ocular pain) than known averages in patients with diabetic retinopathy, central retinal vein occlusion, age-related macular degeneration and low vision, but lower than known averages in a reference group of people without ocular disease. Subscale responses correlated significantly with visual acuity in the involved eye. This observation held true in eight of 12 subscales, even in patients who maintained vision of 20/25 or better in the uninvolved eye. The General Health subscale and number of systemic diseases correlated significantly with both the General Vision and Peripheral Vision subscale scores. There was no correlation between subscale responses and age. CONCLUSIONS: BRVO is a retinal vascular disease that is associated with a decrease in vision-related quality of life as determined by the VFQ-25. A decrease in VFQ-25 score is correlated with involved eye visual acuity, even when good visual acuity is maintained in the uninvolved eye.

The presence of T-lymphocyte subpopulations (CD4 and CD8) in pterygia: evaluation of the inflammatory response.

INTRODUCTION: The aim of our study was to confirm the presence of inflammatory T-lymphocyte subpopulations (CD4 and CD8) in pterygium specimens with regards to clinical severity. Additionally, we examined the effect of topical anti-inflammatory agents on the presence of T-lymphocyte subpopulations. METHODS: Pterygia from nineteen eyes of nineteen patients who underwent surgical excision at Duke University, North Carolina, were included in this study. Normal conjunctiva from one patient was included as a control. Pterygia were pre-operatively graded as mild, moderate or severe based on objective signs of inflammation. Immunohistochemical staining for both CD4 and CD8 subpopulations of T lymphocytes was performed. Distribution of lymphocytes within the epithelium and substantia propria was graded by a masked observer on the following scale: 0 (none/rare), 1+ (mild), 2+ (moderate), or 3+ severe. Statistical analysis was performed using the Fisher exact test and Chi-square test. RESULTS: A total of 16 (84%) pterygia specimens stained for T lymphocytes displayed approximately equal CD4 and CD8 infiltration of both the epithelium and the substantia propria. The majority of CD4 and CD8 lymphocytes were located in aggregates in the epithelium and upper substantia propria. The control specimen contained scant evidence of lymphocytic infiltration. There was no significant difference in the amount of lymphocytic infiltration between mild, moderate or severe pterygia. There was also no significant difference in lymphocytic infiltration between patients with (n=8) or without (n=11) a history of topical anti-inflammatory use. CONCLUSION: The presence of CD4 and CD8 lymphocytes was confirmed in pterygia. There was no significant difference in lymphocytic infiltrate in patients with or without prior topical anti-inflammatory use. Based on these findings, topical immunomodulators may have an adjunctive role in the treatment of pterygia.