Subconjunctival dendrimer-drug therapy for the treatment of dry eye in a rabbit model of induced autoimmune dacryoadenitis.

PURPOSE: To investigate the efficacy of a single subconjunctival injection of dendrimer-dexamethasone conjugate in a rabbit model of induced autoimmune dacryoadenitis (AID). METHODS: Dendrimer biodistribution after subconjunctival injection in AID animals was evaluated using Cy5-labelled dendrimer (D-Cy5) and confocal microscopy. Diseased animals were treated with free dexamethasone (Free-Dex), dendrimer-dexamethasone (D-Dex), or saline via a single subconjunctival injection. The efficacy was evaluated using various clinical evaluations, such as Schirmer's test, tear breakup time (TBUT), and fluorescein and rose Bengal staining. Histopathology was evaluated by H&E staining and immunostaining. Levels of inflammatory cytokines and aquaporin proteins in the LGs were determined by real-time PCR. RESULTS: Subconjunctivally administered dendrimers selectively localized in the inflamed LGs, and were taken up by the infiltrating cells. At two weeks post single dose-treatment, the D-Dex group showed improved clinical evaluations. No significant changes were observed in other groups. H&E staining demonstrated less inflammatory cell infiltration and fewer atrophic acini in D-Dex group, compared to those treated with saline or Free-Dex. Immunohistochemistry demonstrated that the intensity of CD-18 (+) and RTLA (+) was weaker in LGs in the D-Dex group than in other treatment groups. Pro-inflammatory gene expression levels of MMP9, IL6, IL8, and TNFα were significantly decreased in the D-Dex group compared to the Free-Dex and saline group. CONCLUSIONS: The dendrimer exhibits pathology-dependent biodistribution in the inflamed LGs. Subconjunctivally administered D-Dex suppressed LG inflammation, leading to partial recovery of LG function with clinical improvement in induced AID. Sjögren's patients may benefit from this targeted nanomedicine approach.

Chondroitin Sulfate-Based Biocompatible Crosslinker Restores Corneal Mechanics and Collagen Alignment.

Purpose: To evaluate the crosslinking effect of functionalized chondroitin sulfate (CS) in an ex vivo rabbit cornea model. Methods: Chondroitin sulfate molecules were chemically modified with the N-hydroxysuccinimide (NHS) group. Enucleated rabbit eyes were crosslinked with 2, 5, or 10 mg/mL CS-NHS solution for 30 or 60 minutes. The CS-NHS penetration, corneal swelling ratio, Young's modulus, and ultrastructure of the crosslinked corneas were characterized. In addition, rabbit corneas were further treated with a collagenase-chondroitinase solution to create an ex vivo keratoconus (KC)-like model. The KC model corneas were crosslinked with a standard riboflavin-ultraviolet (UV) method or alternatively with CS-NHS. Corneal mechanics, ultrastructure, and keratocyte gene expression were evaluated after UV and CS-NHS crosslinking. Results: CS-NHS effectively penetrated into the corneal stroma within 60 minutes of treatment initiation. CS-NHS crosslinking reduced the swelling ratio by 35%, increased Young's modulus by 20%, and increased collagen fibril diameter and density. CS-NHS crosslinking improved corneal mechanics of KC model corneas to levels comparable to those with UV crosslinking. Moreover, CS-NHS crosslinking demonstrated significant downregulation of proinflammatory gene expression of keratocytes, indicating a potential protective effect imparted by CS-NHS during crosslinking. Conclusions: Our results demonstrated that CS-NHS can reinforce normal and KC model corneal mechanics, and restore collagen density and alignment in KC model corneas without causing extensive keratocyte apoptosis and proinflammatory gene upregulation. Therefore, CS-NHS crosslinking can potentially provide an effective, safe, and biocompatible means of corneal reinforcement.

Comparison of 20% sulfur hexafluoride with air for intraocular tamponade in Descemet membrane endothelial keratoplasty (DMEK).

PURPOSE:: To compare the effect of 20% sulfur hexafluoride (SF6) with that of air on graft detachment rates for intraocular tamponade in Descemet membrane endothelial keratoplasty (DMEK). METHODS:: Forty-two eyes of patients who underwent DMEK by a single surgeon (A.S.J.) at Wilmer Eye Institute between January 2012 and 2014 were identified; 21 received air for intraocular tamponade and the next consecutive 21 received SF6. The main outcome measure was the graft detachment rate; univariate and multivariate analyses were performed. RESULTS:: The graft detachment rate was 67% in the air group and 19% in the SF6 group (p<0.05). No complete graft detachments occurred, and all partial detachments underwent intervention with injection of intraocular air. The percentages of eyes with 20/25 or better vision were not different between the groups (67% vs. 71%). Univariate analysis showed significantly higher detachment rates with air tamponade (OR, 8.50; p<0.005) and larger donor graft size (OR, 14.96; p<0.05). Multivariate analysis with gas but not graft size included showed that gas was an independent statistically significant predictor of outcome (OR, 6.65; p<0.05). When graft size was included as a covariate, gas was no longer a statistically significant predictor of detachment but maintained OR of 7.81 (p=0.063) similar to the results of univariate and multivariate analyses without graft size. CONCLUSION:: In comparison with air, graft detachment rates for intraocular tamponade in DMEK were significantly reduced by 20% SF6.

Comparison of 20% sulfur hexafluoride with air for intraocular tamponade in Descemet membrane endothelial keratoplasty (DMEK) / Comparação de hexafluoreto de enxofre a 20% com ar para tamponamento intraocular na ceratoplastia endotelial de membrana Descemet (DMEK)

ABSTRACT Purpose: To compare the effect of 20% sulfur hexafluoride (SF6) with that of air on graft detachment rates for intraocular tamponade in Descemet membrane endothelial keratoplasty (DMEK). Methods: Forty-two eyes of patients who underwent DMEK by a single surgeon (A.S.J.) at Wilmer Eye Institute between January 2012 and 2014 were identified; 21 received air for intraocular tamponade and the next consecutive 21 received SF6. The main outcome measure was the graft detachment rate; univariate and multivariate analyses were performed. Results: The graft detachment rate was 67% in the air group and 19% in the SF6 group (p<0.05). No complete graft detachments occurred, and all partial detachments underwent intervention with injection of intraocular air. The percentages of eyes with 20/25 or better vision were not different between the groups (67% vs. 71%). Univariate analysis showed significantly higher detachment rates with air tamponade (OR, 8.50; p<0.005) and larger donor graft size (OR, 14.96; p<0.05). Multivariate analysis with gas but not graft size included showed that gas was an independent statistically significant predictor of outcome (OR, 6.65; p<0.05). When graft size was included as a covariate, gas was no longer a statistically significant predictor of detachment but maintained OR of 7.81 (p=0.063) similar to the results of univariate and multivariate analyses without graft size. Conclusion: In comparison with air, graft detachment rates for intraocular tamponade in DMEK were significantly reduced by 20% SF6.

RESUMO Objetivo: Comparar as taxas de descolamento do botão endotelial com o uso de gás hexafluoreto de enxofre a 20% (SF6) em relação ao ar para o tamponamento intraocular na ceratoplastia endotelial da membrana de Descemet (DMEK). Métodos: Quarenta e dois olhos foram operados com a técnica de DMEK por um único cirurgião (A.S.J.) no Wilmer Eye Institute entre janeiro de 2012 a 2014. Os primeiros 21 olhos receberam ar para o tamponamento intraocular após o enxerto do botão endotelial e os 21 olhos seguintes receberam SF6. O desfecho primário medido foi a taxa de descolamento do botão endotelial por análise univariada e multivariada. Resultados: A taxa de descolamento do botão endotelial foi de 67% no grupo que recebeu ar vs 19% no grupo que recebeu SF6 (p<0,05). Não houve nenhum descolamento total de botão e todos os parciais foram tratados com injeção de ar intraocular. Não houve diferença estatística significativa entre os grupos em relação a AV de 20/25 ou melhor (67% vs 71%). A análise univariada demonstrou maior taxa de descolamento com o tamponamento por ar intraocular (OR 8,50, p<0,005) e com botões doadores maiores (OR 14,96, p<0,05). Na análise multivariada, incluindo gás, mas não o tamanho do botão doador, o tipo de gás usado permaneceu sendo um fator preditivo independente e estatisticamente significativo para o desfecho primário, com OR de 6,65 (p<0,05). Porém, quando o tamanho do botão doador foi incluso como covariável, o gás perdeu a sua significância como preditor de descolamento, mantendo o OR de 7,81 (p=0,063), semelhante as análises univariada e multivariada excluindo o tamanho do botão doador. Conclusão: O uso de gás hexafluoreto de enxofre a 20% (SF6) para o tamponamento intraocular reduz a taxa de descolamento do botão endotelial quando comparado ao uso de ar no DMEK.

Three-Dimensional Culture of Functional Adult Rabbit Lacrimal Gland Epithelial Cells on Decellularized Scaffold.

Aqueous tear-deficient dry eye disease is a multifactorial chronic disorder, in which the lacrimal gland fails to produce enough tears to maintain a healthy ocular surface. Some severe cases may develop corneal damage and significant vision loss. Treatment primarily involves palliation using ocular surface lubricants, but can only provide temporary relief. Construction of a bioengineered lacrimal gland having functional secretory epithelial cells is a potentially promising option for providing long-term relief to severe dry eye patients. Using sphere-forming culture techniques, we cultured adult rabbit lacrimal gland progenitor cells and prepared a lacrimal gland scaffold by decellularization. When progenitor cells were seeded onto the decellularized scaffold, they formed duct- and acinar-like structures in the three-dimensional culture system. Lacrimal gland epithelial cells showed good cell viability, cell differentiation, and secretory function in decellularized lacrimal gland matrix, as indicated by morphology, immunostaining, and ß-hexosaminidase secretion assay. This study demonstrated the potential suitability of utilizing tissue-specific progenitor cells and a tissue-derived bioscaffold for lacrimal gland restoration.

Protective Effects of Soluble Collagen during Ultraviolet-A Crosslinking on Enzyme-Mediated Corneal Ectatic Models.

Collagen crosslinking is a relatively new treatment for structural disorders of corneal ectasia, such as keratoconus. However, there is a lack of animal models of keratoconus, which has been an obstacle for carefully analyzing the mechanisms of crosslinking and evaluating new therapies. In this study, we treated rabbit eyes with collagenase and chondroitinase enzymes to generate ex vivo corneal ectatic models that simulate the structural disorder of keratoconus. The models were then used to evaluate the protective effect of soluble collagen in the UVA crosslinking system. After enzyme treatment, the eyes were exposed to riboflavin/UVA crosslinking with and without soluble type I collagen. Corneal morphology, collagen ultrastructure, and thermal stability were evaluated before and after crosslinking. Enzyme treatments resulted in corneal curvature changes, collagen ultrastructural damage, decreased swelling resistance and thermal stability, which are similar to what is observed in keratoconus eyes. UVA crosslinking restored swelling resistance and thermal stability, but ultrastructural damage were found in the crosslinked ectatic corneas. Adding soluble collagen during crosslinking provided ultrastructural protection and further enhanced the swelling resistance. Therefore, UVA crosslinking on the ectatic model mimicked typical clinical treatment for keratoconus, suggesting that this model replicates aspects of human keratoconus and could be used for investigating experimental therapies and treatments prior to translation.

Dry eye disease: A review of diagnostic approaches and treatments.

Dry eye (DE) is a common ocular disease that results in eye discomfort, visual disturbance and substantially affects the quality of life. It has a multifactorial etiology involving tear film instability, increased osmolarity of the tear film and inflammation of the ocular surface with potential damage to the ocular surface. This review discusses the classification, diagnostic approaches and treatments of DE.

Stem cell-based therapy for treating limbal stem cells deficiency: A review of different strategies.

The self renewal capability of limbal epithelial stem (LEST) cells is fundamental to the maintenance and healing of corneal epithelium. Limbal stem cell deficiency (LSCD), due to dysfunction or loss of LEST cells, therefore presents as persistent epithelial defects, corneal vascularization, conjunctivalization etc. Stem cell-based therapy, in its simplest form - limbal autograft, has been used successfully for more than a decade. For bilateral LSCD, similar approaches with limbal allografts have been unsuccessful largely due to strong immune rejection. Therefore, as an alternate strategy for treating bilateral LSCD, ex vivo expansion of the remaining LEST cells or autologous stem cells sourced from other potential sites is being explored. Different culture systems (with and without xenobiotic supplements) using substrates like amniotic membrane or fibrin gels have been used successfully for ex vivo LEST cell maintenance and reproduction by imitating the stem cell niche. This paper is organized into sections reviewing the LEST cells, LSCD and various stem cell-based approaches for treating LSCD and discussing future direction and challenges.

Ocular surface rehabilitation: Application of human amniotic membrane in high-risk penetrating keratoplasties.

BACKGROUND: Human amniotic membrane is a versatile tool for management of ocular surface disorders. This study evaluates the effect of cryopreserved human amniotic membrane (hAM) on one-year survival of penetrating keratoplasties (PKP) in high-risk recipients. METHOD: This is a retrospective noncomparative cohort study of 58 consecutive eyes undergoing PKP with concurrent placement of a self-retained cryopreserved hAM (PROKERA®) at a tertiary care center from January 2009 to July 2010. RESULTS: Mean patient age was 66.7 ± 17.2 years and 30 (54%) were males. 51 eyes were pseudophakic and one aphakic. 27 eyes were glaucomatous; 24 had glaucoma drainage device and 2 had previous endocyclophotocoagulation. 12 patients had PKP for the first time and 46 had repeat PKP (average number of prior PKP = 1.63 ± 1.1, range: 1-5). Risk factors for graft failure included repeat PKP (79.3%), corneal neovascularization (51.7%), preexisting glaucoma (46.6%), and presence of anterior synechiae (37.9%). Both First Transplant and Repeat Transplant groups had similar survival rates until 6 months after transplant (75% vs 74%, odds ratio = 1.06, p = 1.00). At 12 months, First Transplant group showed a better survival rate (67% vs 43%, odds ratio = 2.60, p = 0.20). Eyes with >3 risk factors had a higher graft failure rate (odds ratio = 5.81, p = 0.003). CONCLUSION: Survey of the literature suggests that high-risk PKP with concurrent hAM placement demonstrate comparable graft survival. Presence of multiple risk factors is associated with poor survival.

Induction of endothelial RAGE expression in pterygium.

PURPOSE: Chronic inflammation is a critical process in pterygium development and progression, including promotion of angiogenesis. Vascular endothelial cells (ECs) actively participate in and regulate inflammation. Pterygium research has uncovered multiple inflammatory cytokines that are upregulated, but there has been minimal focus on EC activation. The Receptor for Advanced Glycation Endproducts (RAGE), a major proinflammatory molecule expressed in the vascular endothelium and other cell types, is a major instigator of endothelial cell activation. In this study, we explored the hypothesis that RAGE is upregulated in ECs in pterygium. To this end, we examined RAGE expression and immunolocalization in human pterygium and normal conjunctival tissue, with a particular interest in assessing endothelial RAGE. METHODS: Pterygium specimens were obtained from 25 patients during surgery at the King Khaled Eye Specialist Hospital (KKESH). In the same patients, conjunctiva were obtained from the autograft during surgery. Tissue specimens were formalin-fixed and paraffin-embedded. Tissue sections were analyzed with immunohistochemistry with anti-RAGE antibody. Expression and localization of RAGE were evaluated in pterygium and corresponding conjunctiva. RESULTS: RAGE expression was detected in the vascular endothelium in all pterygium tissue specimens and most conjunctival specimens. Other cell types exhibited expression, notably epithelial cells, fibroblasts, and possibly macrophages. Strikingly, endothelial RAGE expression was increased in 19 of 25 pterygium tissue specimens, compared to the corresponding control conjunctiva. CONCLUSIONS: Our data reveal that RAGE expression is upregulated in vascular endothelial cells in pterygium. RAGE upregulation is an important mechanism by which endothelial cells amplify the overall inflammatory response, and suppression of RAGE has been shown to prevent the progression of some systemic disease processes in experimental models. This suggests that pharmacologic targeting of RAGE, which is already being attempted in clinical trials for some diseases, could be useful in treating pterygium.

Descemet stripping with automated endothelial keratoplasty: A comparative study of outcome in patients with preexisting glaucoma.

PURPOSE: To compare postoperative complications after Descemet stripping with automated endothelial keratoplasty (DSAEK) in patients with and without glaucoma. METHODS: For this retrospective study a series of 298 DSAEK cases performed at the Doheny Eye Institute were taken, we compared postoperative complications in eyes with glaucoma on medication (55) or with previous glaucoma surgeries (64) with a time-matched group of all other DSAEK cases (179, control). RESULTS: With a mean follow-up of 1.85 ± 1.12 years, the complication rates were 12.8%, 11.1%, and 26.8% for postoperative graft detachment, graft failure, and IOP elevation, respectively. Graft detachment was an independent risk factor for graft failure (odds ratio OR = 12.35, 95% confidence interval CI [5.46-27.90], P < 0.001). Graft detachment was not associated with either history of glaucoma or glaucoma surgery (P > 0.05). Glaucoma on medication had no increased risks of graft failure compared to normal eyes (P = 0.38). However, increased risk of failure was seen in eyes with prior incisional glaucoma surgeries (OR = 4.26, 95% CI [1.87-9.71], P < 0.001). Medically managed glaucoma has increased risks of postoperative IOP elevation (OR = 2.39, 95% CI [1.25-4.57], P = 0.013), whereas surgically managed glaucoma has no significant elevation (P = 0.23). Elevation of IOP was not significantly correlated with graft failure (P = 0.21). CONCLUSION: DSAEK is the preferred treatment for corneal endothelial dystrophy. We observed that having glaucoma or glaucoma surgery is not associated with graft detachment. A history of glaucoma surgery and postoperative graft detachment appeared to be important risk factors for graft failure. And more studies are indicated to study long-term IOP evolution in post-DSAEK patients and its association with graft survival.

Acute hydrops in the donor cornea graft in non-keratoconus patients.

A 44-year-old Hispanic male and 91-year-old Caucasian male presented to the clinic with acute vision loss and pain years after penetrating keratoplasty (PKP). Neither patient had a history of keratoconus. Both patients had a history of eye rubbing and intraocular device present in the anterior chamber. The first patient had a history of a glaucoma drainage tube and the second patient had an anterior chamber intraocular lens implanted. Anterior segment ocular coherence tomography showed deep stromal cystic cavities. Both patients exhibited breaks in the endothelium by ultrasound biomicroscopy and the histopathologic examination after repeat PKP. Those findings were most consistent with acute corneal hydrops in the donor graft.

Strategies for local gene therapy of corneal allograft rejection.

Penetrating keratoplasty is the most common type of tissue transplant in humans. Irreversible immune rejection leads to loss of vision and graft failure. This complex immune response further predisposes future corneal transplants to rejection and failure. A diverse armamentarium of surgical and pharmacologic tools is available to improve graft survival. In this review, we will discuss the various gene therapeutic strategies aimed at potentiating the anterior chamber-associated immune deviation to extend graft survival.

Diverse mediators modulate the chloride ion fluxes that drive lacrimal fluid production.

PURPOSE: To learn whether locally expressed and systemic mediators might modulate the cholinergically induced transepithelial Cl(-) fluxes that underlie lacrimal fluid production. METHODS: Reconstituted epithelial monolayers were exposed to a submaximal dose of the muscarinic agonist, carbachol (CCh), or to one of several paracrine mediators for 18 hours, then acutely stimulated with an optimal dose of CCh. Secretory Cl(-) fluxes were assessed as negative short-circuit currents (ISC). RESULTS: Exposure to IL-6 at concentrations of 1 and 10 ng/mL and IL-1ß at 10 ng/mL significantly decreased CCh-induced Cl(-) secretion. Prolactin decreased CCh-induced Cl(-) secretion, but the extent of the decrease diminished as the prolactin concentration increased from 20 to 200 ng/mL. CCh, 10 µM, prevented CCh, 100 µM, from eliciting Cl(-) secretion. Exposure to histamine, 10 mM, prevented formation of confluent monolayers. Exposure to histamine, 1 mM, decreased CCh-induced Cl(-) secretion, whereas exposure to 5-HT, 1 mM, potentiated CCh-induced Cl(-) secretion. CONCLUSIONS: Chronic exposure to inflammatory cytokines may significantly impair cholinergically induced lacrimal fluid production. Concentrations of prolactin within the high range of normal values also may impair fluid production, but this effect is reversed at levels associated with pregnancy. Autonomic neurotransmitters and paracrine mediators that signal through different G protein-coupled receptors appear to exert varying influences, which range from complete suppression to potentiation of cholinergically induced fluid production. Thus, some hormones and paracrine mediators may impair secretion in apparently homeostatic glands as well as diseased glands, whereas mediators produced by certain immune cell infiltrates may actually enhance fluid formation.

Imaging studies in a case of infectious scleritis after pterygium excision.

A 44-year-old woman presented with a painful red eye for 2 weeks. Ultrasound biomicroscopy and optical coherence tomography were instrumental in the diagnosis and management of this case of infectious scleritis associated with previous pterygium excision complicated by choroidal and retinal detachments.

Correlation between optical coherence tomography-derived assessments of lower tear meniscus parameters and clinical features of dry eye disease.

PURPOSE: To measure the correlation between subjective symptom score, conventional clinical tests, and Fourier-domain optical coherence tomography (FD-OCT) of lower tear meniscus parameters in patients with dry eye disease. METHODS: Eighteen patients with dry eye disease requiring medical therapy and/or punctal occlusion were recruited for this prospective, nonrandomized, observational case series. Severity of symptoms of dry eye disease was assessed using the Indiana University Dry Eye Questionnaire 2002. Clinical assessments were completed using slit-lamp biomicroscopy, rose bengal dye staining, fluorescein tear breakup time (TBUT), and a 5-minute Schirmer test with topical anesthesia. The lower tear meniscus was imaged using an FD-OCT system with 5-µm axial resolution and measured manually by a masked grader using computer calipers. Correlation was assessed using Spearman correlation coefficient (ρ). RESULTS: The mean (±SD) scaled symptom score was 58 ± 21, with a range of 0 to 100. Vital staining test averaged 1.7 ± 3.4, TBUT averaged 4.4 ± 1.8 seconds, and Schirmer tests averaged 10.2 ± 8.1 mm. As determined by optical coherence tomography, the meniscus height was 228 ± 153 µm, depth was 127 ± 79 µm, and cross-sectional area was 0.018 ± 0.021 mm. Optical coherence tomography meniscus area was negatively correlated with the symptom questionnaire score (P < 0.01) and positively correlated with Schirmer test results (P < 0.01). There was no significant correlation between symptom score and rose bengal staining, TBUT, or Schirmer test results (P > 0.01). CONCLUSIONS: Lower tear meniscus measurement with FD-OCT is an objective noninvasive test that correlates well with symptoms of dry eye disease and the Schirmer test.

Early surgical debridement in the management of infectious scleritis after pterygium excision.

PURPOSE: The purpose of this study was to report outcomes of infectious scleritis after pterygium surgery, managed with antibiotic therapies and early scleral debridement. METHODS: Retrospective chart review of 13 consecutive cases of infectious scleritis after pterygium excision between 1999 and 2009 was conducted. Collected data included prior medical and surgical history, latency period between pterygium surgery and presentation of infectious scleritis, culture and histopathologic findings, antibiotic regimen, length of hospital stay, visual acuity before and after treatment, and complications. RESULTS: Median follow-up was at 14 months. Twelve patients underwent prompt surgical debridement after infectious scleritis diagnosis (median, 2.5 days). Debridement was delayed in one patient. Median hospital stay was 3 days. Best-corrected visual acuity improved in ten patients, remained stable in one patient, and decreased in two patients following treatment. Complications included scleral thinning requiring scleral patch graft (1/13), glaucoma (3/13), and progression to phthisis bulbi (1/13). No patients required enucleation. CONCLUSIONS: In contrast to the generally poor outcomes in the literature, early surgical debridement of pterygium-associated infectious scleritis appears to offer improved prognosis.

Between-grader repeatability of tear meniscus measurements using Fourier-domain OCT in patients with dry eye.

BACKGROUND AND OBJECTIVE: To examine the between-grader repeatability of height, depth, and cross-sectional area measurements of the lower tear meniscus, using a Fourier-domain optical coherence tomography (OCT) system. PATIENTS AND METHODS: A total of 16 patients with dry eye had the lower tear meniscus of the right eye imaged twice in rapid succession. The tear meniscus height, depth, and cross-sectional area were measured by two masked graders using computer calipers. The between-grader variability, calculated using the pooled coefficient of variation (CV%), assessed the repeatability of the measurements. RESULTS: The between-grader CV% was 12.1%, 15.7%, and 19.5% for height, depth, and area, respectively. The between-image variability was 17.1%, 13.4%, and 35.4% for height, depth, and area, respectively. The overall intraclass correlation was 99%. There was no systematic bias between the two graders. CONCLUSION: Fourier-domain OCT demonstrates good between-grader and between-image repeatability in measuring the height, depth, and cross-sectional area of the tear meniscus in patients with dry eye. Measurement variability was primarily due to the difference between images rather than graders.