Hemangiosarcoma in dogs as a potential non-rodent animal model for drug discovery research of angiosarcoma in humans.

Since the domestication of dogs 10,000 years ago, they have shared their living environment with humans and have co-evolved. The breeding process that dogs have undergone in only a few centuries has led to a significant accumulation of specific genetic alterations that could induce particular diseases in certain breeds. These canine diseases are similar to what is found in humans with several differences; therefore, comparing such diseases occurring in humans and dogs can help discover novel disease mechanisms, pathways, and causal genetic factors. Human angiosarcoma (AS) and canine hemangiosarcoma (HSA), which are sarcomas originating from endothelium, are examples of diseases shared between humans and dogs. They exhibit similar characteristics and clinical behaviors, although with some critical differences resulting from evolution. In this review, we will describe the similarities and differences in terms of clinical and molecular characteristics between human AS and canine HSA, and discuss how these similarities and differences can be applied to advance the treatment of these diseases.

Insights into the clinical development of regenerative medical products through a comparison of three cell-based products recently approved for limbal stem cell deficiency.

Three regenerative medical products for limbal stem cell deficiency (LSCD), a rare and intractable ocular surface disease, have recently been approved in Japan. To our knowledge, this is the first time multiple stem-cell-based medical products have been approved for the same ocular disease. Development plans and study designs for each product differ, resulting in differences in indications. Since cell-based products have a heterogeneous formulation and often target rare diseases, they require a flexible approach to development. This review article describes the status and prospects of the clinical development of regenerative medical products by summarizing the issues of the three products from the Pharmaceuticals and Medical Devices Agency (PMDA) standpoint. Implementing stem cell-based products is challenging, requiring scientific and flexible review by regulatory authorities. To overcome these issues in the development process, developers and regulatory authorities need to communicate and fully discuss study protocols from the early stage of development.

The Impact of Noncontact Tonometry and Icare Rebound Tonometry on Tear Stability and Dry Eye Clinical Practice.

The purpose of this study was to investigate the possible effects of the noncontact air puff tonometry (NCT) and Icare rebound tonometry (ICT) on the tear film stability by using the tear stability analysis system (TSAS) and dry eye parameters. Fifteen eyes from fifteen normal healthy subjects were investigated in this study. All subjects underwent TSAS surface regularity index (SRI) examinations, TBUT, and IOP measurements. The mean IOP results measured with NCT were 13.3 ± 1.86 mm Hg, and the mean IOP results measured with ICT were 15.88 ± 3.09 mm Hg (p > 0.05). The mean values of baseline, 5 min, and 10 min of the NCT-SRI and ICR-SRI were tested. There were statistically significant differences between NCT-Baseline SRI, NCT-5 min SRI, and NCT-10 min SRI values (p < 0.05). SRI values significantly increased after NCT. The mean values of the baseline, 5 min, and 10 min of the ICT-SRI were also assessed. There were no statistically significant differences between ICT-Baseline SRI, ICT-5 min SRI, and ICT-10 min SRI values (p > 0.05). The mean TBUT values exhibited a significant decrease at 1 min, 5 min, and 10 min compared with baseline values for the NCT and ICT (p < 0.01). NCT-TBUT and ICT-TBUT values were also compared with each other in the same time period. There were no statistically significant differences between NCT-Baseline and ICT-Baseline TBUT values (p > 0.05). In conclusion, intraocular pressure measurements in routine ophthalmology clinical practices by either NCT or ICT cause deterioration in the tear film stability which might affect tear stability testing when performed soon after IOP measurements. It is best to wait at least for 20−30 min after the IOP measurement before evaluating the tear film and the corneal surface or perform tonometry after the tear film-ocular surface evaluation tests.

Smart Eye Camera: A Validation Study for Evaluating the Tear Film Breakup Time in Human Subjects.

Purpose: This study aimed to demonstrate the efficacy of a "Smart Eye Camera (SEC)" in comparison with the efficacy of the conventional slit-lamp microscope by evaluating their diagnostic functionality for dry eye disease (DED) in clinical cases. Methods: This retrospective study included 106 eyes from 53 adult Japanese patients who visited the Ophthalmology outpatient clinics in Keio University Hospital from June 2019 to March 2020. Tear film breakup time (TFBUT) and corneal fluorescence score (CFS) measurements for the diagnosis of DED were compared between the conventional slit-lamp microscope and SEC. Results: The objective findings of DED showed that there was a strong correlation between the conventional slit-lamp microscope and SEC with respect to TFBUT and CFS results (Spearman's r = 0.887, 95% confidence interval [CI] = 0.838-0.922, and r = 0.920, 95% CI = 0.884-0.945, respectively). The interobserver reliability between the conventional slit-lamp microscope and SEC showed a moderate agreement (weighted Kappa κ = 0.527, 95% CI = 0.517-0.537 and κ = 0.550, 95% CI = 0.539-0.561 for TFBUT and CFS, respectively). The diagnostic performance of the SEC for Asia Dry Eye Society diagnostic criteria showed a sensitivity of 0.957 (95% CI = 0.841-0.992), specificity of 0.900 (95% CI = 0.811-0.927), positive predictive value of 0.880 (95% CI = 0.774-0.912), and negative predictive value of 0.964 (95% CI = 0.869-0.993). Moreover, the area under the receiver operating characteristic curve was 0.928 (95% CI = 0.849-1.000). Conclusions: Compared with the conventional slit-lamp microscope, SEC has sufficient validity and reliability for diagnosing DED in the clinical setting. Translational Relevance: The SEC can portably evaluate TFBUT in both basic research and clinical care.

Clinical Observation of Allergic Conjunctival Diseases with Portable and Recordable Slit-Lamp Device.

BACKGROUND: The incidence of allergic conjunctival diseases (ACDs) is gradually increasing worldwide. Both ophthalmologists and non-ophthalmologists prescribe eye drops to treat ACDs; however, there are many cases which are treated without sufficient examination and diagnosis of the eyes. We have invented a portable, recordable, and smartphone-attachable slit-lamp device-Smart Eye Camera (SEC). The purpose of this study was to compare the diagnostic abilities of ACDs between the SEC and the conventional, non-portable slit-lamp microscope. METHODS: This prospective observational study included 32 eyes of 17 Japanese patients (mean age: 21.5 ± 14.8 years; range: 11-51 years; female: 5). The severity of 10 objective signs in the palpebral conjunctiva, bulbar conjunctiva, limbus, and cornea were scored on a grading scale of 0 to 4 (0 = normal; 1+ = mild; 2+ = moderate; 3+ = severe), respectively. First, the conventional slit-lamp microscope was used to examine the grade of the ACDs. Second, another ophthalmologist filmed the eyes using the SEC and two other ophthalmologists evaluated the grades on another day. The correlation and inter-rater reproducibility in total scores among the two devices were determined. RESULTS: Total scores of clinical signs, evaluated by the two approaches, correlated significantly (both eyes: r = 0.918 (95% CI: 0.839 to 0.959; p < 0.001)), with substantial inter-rater agreement (weighted κ value = 0.631 (95% CI: 0.601 to 0.661; p < 0.001)). CONCLUSIONS: The SEC is as reliable as the conventional non-portable slit-lamp microscope for assessing ACDs.

Two case reports of continued progression of chronic ocular graft-versus-host disease without concurrent systemic comorbidities treated by amniotic membrane transplantation.

BACKGROUND: Chronic ocular graft-versus-host disease (oGVHD) is an ocular comorbidity of graft-versus-host disease (GVHD) that usually occurs concurrently with systemic manifestations. Failure to detect and treat oGVHD in its early stages may lead to progression of ocular signs and symptoms leading to oGVHD that is refractory to conventional treatment. CASE PRESENTATION: We report the clinical course of a 19-year-old male and a 59-year-old female with severe and progressive chronic oGVHD without concurrent systemic signs of chronic graft-versus-host disease (cGVHD). Although their systemic conditions had been stable, both suffered from severe oGVHD and were referred to our clinic. Both cases exhibited marked improvement in conjunctival inflammation and fibrotic changes after amniotic membrane transplantation (AMT). Both cases underwent keratoplasty eventually to stabilize ocular surface conditions and to improve visual function. CONCLUSIONS: We reported the clinical outcomes of 2 cases of chronic oGVHD without concurrent systemic comorbidities that were treated with AMT. The clinician should be aware that cGVHD may persist in target organs even in the absence of concurrent systemic comorbidities following seemingly successful systemic treatment. A multidisciplinary team approach is essential in the early detection and therapeutic intervention for chronic oGVHD.

A Study Validating the Estimation of Anterior Chamber Depth and Iridocorneal Angle with Portable and Non-Portable Slit-Lamp Microscopy.

This study assessed the anterior chamber depth (ACD) and iridocorneal angle using a portable smart eye camera (SEC) compared to the conventional slit-lamp microscope and anterior-segment optical coherence tomography (AS-OCT). This retrospective case-control study included 170 eyes from 85 Japanese patients. The correlation between the ACD evaluations conducted with the SEC and conventional slit-lamp was high (r = 0.814). The correlation between the Van-Herick Plus grade obtained using two devices was also high (r = 0.919). A high kappa value was observed for the Van-Herick Plus grading (Kappa = 0.757). A moderate correlation was observed between the ACD measured using AS-OCT and the slit-lamp image acquired with the conventional slit-lamp microscope and SEC (r = 0.609 and 0.641). A strong correlation was observed between the trabecular-iris angle (TIA) measured using AS-OCT and Van-Herick Plus grade obtained with the conventional slit-lamp microscope and SEC (r = 0.702 and 0.764). Strong correlations of ACD evaluation and high kappa value of the Van-Herick Plus grading indicated the adequate subjective assessment function of the SEC. Moderate correlations between the ACD objective measurement and evaluation and strong correlation between the TIA and Van-Herick Plus grade suggested the good objective assessment function of the SEC. The SEC demonstrated adequate performance for ACD evaluation and angle estimation.

Myopia, corneal endothelial cell density and morphology in a Japanese population-based cross-sectional study: the JPHC-NEXT Eye Study.

This population-based cross-sectional study was performed to determine the mean corneal endothelial cell density (ECD), coefficient of variation (CV), and hexagonality (HEX), and their associations with myopia in Japanese adults living in Chikusei city. Of 7109 participants with available data, 5713 (2331 male and 3382 female) participants were eligible for analysis. After assessing the relationship between participant characteristics and spherical equivalent refraction (SER), the association of SER with the abnormal value of ECD (< 2000 cells/mm), CV (≥ 0.40), and HEX (≤ 50%) were determined using the logistic regression models adjusting for potential confounders (age, intraocular pressure, keratometric power, height, and antihypertensive drug use). In male participants, there was no statistically significant relationships between SER and endothelial parameters. In female participants, compared to emmetropia, SER ≤ - 6 D had significantly higher odds ratio (OR) of having the abnormal value of CV (OR = 2.07, 95% confidence interval [CI] 1.39-3.10) and HEX (OR = 2.04, 95% CI 1.29-3.23), adjusted for potential confounders, indicating that the high myopia was associated with the abnormal values of CV and HEX. Further adjustment for contact lenses wear partly attenuated these associations. Association between the SER and ECD was not detected.

The Overlap Syndrome: A Case Report of Chronic Graft-Versus-Host Disease After the Development of a Pseudomembrane.

BACKGROUND: Ocular graft-versus-host disease (GVHD) is one of the most severe complications of hematopoietic stem cell transplantation. It manifests as an impairment of the ocular surface, such as severe dry eye disease, and deteriorates the recipient's visual function and quality of life. We encountered an "overlap syndrome" of ocular GVHD, which is characterized by the presence of both acute and chronic GVHD symptoms. In this report, we present the treatment progress of the overlap syndrome in a case with ocular GVHD. CASE PRESENTATION: A 57-year-old man with acute myeloblastic leukemia underwent hematopoietic stem cell transplantation. Six weeks after the treatment, the recipient complained of eye pain and discharge. He was diagnosed with the overlap syndrome due to low tear volume, severe corneal epithelitis, hyperemia, and a pseudomembrane on the conjunctiva. Immune cells infiltration, fibrinoid degeneration, fibroblastic and spindle-shaped cells, and fibrosis were observed in the pathology of the pseudomembrane. The recipient was treated with topical immunosuppression and pseudomembrane removal. One week after the initial treatment, ocular GVHD improved. Twelve weeks after the treatment, the topical steroid was discontinued due to the elevation of intraocular pressure. CONCLUSIONS: The assessment of conjunctival pseudomembrane in ocular GVHD is important to determine the stage of the case and to assess systemic GVHD. Furthermore, prompt removal of the pseudomembrane after diagnosis is an appropriate management to reduce the symptoms of ocular GVHD. The combination of topical steroids and immunosuppressive agents is suggested to be an effective treatment in management of overlap syndrome.

Evaluation of Nuclear Cataract with Smartphone-Attachable Slit-Lamp Device.

Background: Visual impairments and age-related eye diseases need to be detected and treated in a timely manner. However, this is often hampered by lack of appropriate medical equipment. We have invented a portable, recordable, and smartphone-attachable slit-lamp device, called the Smart Eye Camera (SEC). The aim of this study was to compare evaluating nuclear cataract (NUC) between the SEC and the conventional, non-portable slit-lamp microscope. Methods: A total of 128 eyes of 64 Japanese patients (mean age: 73.95 ± 9.28 years; range: 51‒92 years; female: 34) were enrolled. The NUC was classified into four grades (grade 0 to 3) based on three standard photographs of nuclear opacities according to the WHO classification by ophthalmologists. An ophthalmic healthcare assistant (non-ophthalmologist) filmed the eyes in video mode by the SEC and an ophthalmologist graded the NUC. Grade correlation and inter-rater reproducibility were determined. Results: NUC grading by the two approaches correlated significantly (both eyes: r = 0.871 [95%CI: 0.821 to 0.907; p < 0.001]). Inter-rater agreement was high (weighted κ = 0.807 [95%CI: 0.798 to 0.816; p < 0.001]). Conclusions: This study suggests that the SEC is as reliable as the conventional non-portable slit-lamp microscope for evaluating NUC.

Corneal higher-order aberrations in eyes with chronic ocular graft-versus-host disease.

PURPOSE: Chronic ocular graft-versus-host disease (GVHD) is a long-term complication after hematopoietic stem cell transplantation (HSCT) and leads to irreversible visual morbidity due to severe ocular surface impairments including visual disfunction. However, knowledge about the optical function in chronic ocular GVHD is limited because it is difficult to assess quantitative optical function objectively. The development of anterior segment optical coherence tomography has allowed objective quantification of optical function by evaluating corneal higher-order aberrations (HOAs). Therefore, we applied this quantification in chronic ocular GVHD patients and verified the correlation between corneal HOAs and visual acuity. METHODS: We retrospectively reviewed chronic ocular GVHD patients and the recipients after HSCT. Then, analyzed the relationship between visual function and the severity of chronic ocular GVHD. RESULTS: The eyes of patients with chronic ocular GVHD had higher corneal HOAs than those of non-GVHD patients (HOAs; 0.481 ±â€¯0.306 vs 0.254 ±â€¯0.084, and 0.917 ±â€¯0.609 vs 0.529 ±â€¯0.130. P < 0.001, and 0.002. 4-mm and 6-mm diameters respectively. Corneal HOAs were correlated with the severity of chronic ocular GVHD (r = 0.436. P < 0.001). Moreover, corneal HOAs were correlated with visual acuity, especially in eyes with severe chronic ocular GVHD cases (HOAs; 4-mm r = 0.636. P = 0.036. Total 6-mm r = 0.871. P =<0.001). CONCLUSIONS: We succeed to assess the objective value in the optical function of the chronic ocular GVHD. Quantification of corneal HOAs could be an objective evaluation to assess optical function in eyes with chronic ocular GVHD.

The Effect of Cytokine-Stimulation and Pharmacologic Intervention on PGE2 Production in Primary Human Conjunctival and Corneal Cells.

We studied the production of PGE2 by human conjunctival and corneal cells in response to inflammation, and reduction of inflammation with non-steroidal anti-inflammatory drugs. Primary cultures of human conjunctival epithelial cells, fibroblasts, corneal epithelial cells, and keratocytes were incubated with IL-4 and TNF-α. PGE2 and COX-2 levels were analyzed. Effects of anti-inflammatory and anti-immune drugs on PGE2 production were also investigated. IL-4 and TNF-α induced the generation of PGE2 and COX-2 in conjunctival and corneal cells. Epithelial PGE2 production was significantly lower than in keratocytes and fibroblasts, which was down-regulated by aspirin. IL-4 and TNF-α enhanced the inflammatory response via prostaglandin production which contributed to ocular surface inflammation. Prostaglandin production was higher in stromal cells than epithelial cells. These results suggest that the epithelial barrier disruption may contribute to ocular allergic inflammation by the PGE2 production from stromal cells. Moreover, NSAIDs were effective in suppressing PGE2 production in our experiment.

"Smart Eye Camera": An innovative technique to evaluate tear film breakup time in a murine dry eye disease model.

Tear film breakup time (TFBUT) is an essential parameter used to diagnose dry eye disease (DED). However, a robust method for examining TFBUT in murine models has yet to be established. We invented an innovative device, namely, the "Smart Eye Camera", which addresses several problems associated with existing methods and is capable of evaluating TFBUT in a murine DED model. We compared images taken by existing devices and the Smart Eye Camera in a graft-versus-host disease-related DED murine model. We observed that the quality of the images obtained by the Smart Eye Camera were sufficient for practical use. Moreover, this new technique could be used to obtain measurements for several consecutive ocular phenotypes in a variety of environments. Here, we demonstrate the effectiveness of our new invention in the examination of ocular phenotypes, including TFBUT in a murine model. We highlight the potential for future translational studies adopting the Smart Eye Camera in clinical settings.

The efficacy of 0.1% tacrolimus ophthalmic suspension in the treatment of severe atopic keratoconjunctivitis.

BACKGROUND: Severe atopic keratoconjunctivitis (AKC) is a relatively rare disease, and some cases are refractory to conventional steroid treatment. OBJECTIVE: To examine the efficacy of 0.1% tacrolimus ophthalmic suspension in treating severe AKC during a 1-year follow-up. METHODS: This was a single-center, retrospective clinical study. Sixty eyes from 30 patients with severe AKC who were treated with 0.1% tacrolimus ophthalmic suspension 4 times per day, were included. The mean age of the patients was 21.5 ± 13.7 years. The severity of objective signs was observed at baseline (before treatment), at 2 weeks, and at 1, 2, 3, 6, and 12 months after treatment initiation. Ten objective signs of palpebral conjunctiva, bulbar conjunctiva, limbus, and cornea were assessed using 4 grades (0 = normal; 1+ = mild; 2+ = moderate; 3+ = severe). Safety was assessed based on the incidence and the severity of adverse events. RESULTS: The total score of the 10 clinical signs significantly decreased from baseline 2 weeks after initiating tacrolimus eye drop treatment, except at 2 months. The mean total score of clinical signs was 13.6 ± 6.6 at the beginning of treatment, and decreased to 5.4 ± 4.8 12 months after initiation. Treatment was gradually tapered, with increasing intervals between applications. Additional medications were required to provide relief in 18 patients during follow-up. No patient discontinued treatment due to adverse drug effects. Herpes keratitis was observed in 3 cases during follow-up. However, these cases were completely controlled. CONCLUSION: The 0.1% tacrolimus ophthalmic suspension is effective for the treatment of severe AKC refractory to standard conventional treatments throughout a full year.

Efficacy of Plate Expression of Meibum on Tear Function and Ocular Surface Findings in Meibomian Gland Disease.

PURPOSE: To evaluate the clinical effectiveness of expression treatment on meibomian gland disease (MGD). METHODS: Seventeen right eyes of 17 patients with MGD were divided into 3 groups in this randomized prospective clinical study: no expression group: routine treatment with no expression (five patients, five eyes); digital expression group: routine treatment with digital expression (five patients, five eyes); and plate expression group: routine treatment with plate expression (seven patients, seven eyes). All groups received the same routine treatment for 1 month. Tear film break-up time (TBUT), vital staining scores, meibum expressibility, and the dry eye-related quality of life score (DEQS) questionnaire results were assessed before and 1 month after treatment. RESULTS: There was a statistically significant difference of posttreatment TBUT among groups as determined by one-way analysis of variance (P<0.05). A post hoc test revealed that TBUT was statistically significantly higher in plate expression group compared with digital expression group. The fluorescein staining score did not show a statistically significant difference among the groups. Meibum expressibility and the DEQS scores improved in all groups. CONCLUSION: Plate expression when used as an adjunct to routine medical management of MGD has been found to be a comparatively effective treatment in terms of improvement of tear film stability compared with no expression or digital expression.

Effect of Ultrasonic Moisture Glasses on Dry Eye Signs and Symptoms.

PURPOSE: This study was undertaken to evaluate the effect of a novel humidifying eyeglass-shaped device-ultrasonic moisture glasses-on dry eye signs and symptoms. METHODS: A total of 18 subjects with dry eye symptoms underwent a crossover test. A water cartridge was set on each temple of the eyeglass-shaped device. All subjects randomly wore the device twice in different settings, each for 10 minutes. Subjects wore the glasses once with the cartridges filled with water (the intervention group), and once with the cartridges empty (the control group). The order was randomized. We evaluated tear film break-up time (TBUT) and fluorescein staining score just before, immediately after, and 10 minutes after wearing the device. We also assessed functional visual acuity (FVA), blink frequency, and visual analog scale (VAS) score just before and immediately after wearing the device. RESULTS: TBUT, blink frequency, and VAS improved in the intervention group (all P < 0.001) and exhibited significant differences between the intervention and control groups. CONCLUSIONS: Wearing the ultrasonic moisture glasses for 10 minutes improved tear stability and decreased dry eye symptoms in this cohort of subjects. TRANSLATIONAL RELEVANCE: These findings show that the ultrasonic moisture glasses are an effective device for improving dry eye signs and symptoms.

Preoperative Aqueous Cytokine Levels are Associated With Endothelial Cell Loss After Descemet's Stripping Automated Endothelial Keratoplasty.

Purpose: To evaluate the association between endothelial cell density (ECD) after Descemet's stripping automated endothelial keratoplasty (DSAEK) and preoperative cytokine levels in the aqueous humor (AqH). Methods: This prospective consecutive case series included 97 consecutive patients who underwent DSAEK (64 eyes) or cataract surgery (33 eyes). AqH samples were collected at the beginning of each surgery. The levels of cytokines (IL-1α, IL-1ß, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17A, IFN-α, IFN-γ, monocyte chemotactic protein [MCP]-1, E-selectin, P-selectin, and soluble intercellular adhesion molecule [sICAM]-1) in the AqH were measured by multiplex beads immunoassay. The correlations between preoperative aqueous cytokine levels and the ECD at 12 months after DSAEK were analyzed. Results: The ECD decreased from 2747 ± 259 cells/mm2 in the donor graft to 1235 ± 607 cells/mm2 at 12 months after DSAEK. In all subjects undergoing DSAEK, the postoperative ECD at 12 months was significantly correlated with the preoperative levels of MCP-1 (r = -0.467, 95% confidence interval [CI]: -0.650 to -0.222, P = 0.0003). In an analysis excluding Fuchs endothelial corneal dystrophy (11 eyes), the ECD at 12 months after DSAEK was significantly correlated with preoperative levels of IL-17A (r = -0.635, 95% CI: -0.819 to -0.319, P = 0.0004), MCP-1 (r = -0.605, 95% CI: -0.779 to -0.345, P < 0.0001), IFN-γ (r = -0.633, 95% CI: -0.796 to -0.385, P < 0.0001), E-selectin (r = -0.516, 95% CI: -0.756 to -0.276, P = 0.0004), and sICAM-1 (r = -0.537, 95% CI: -0.735 to -0.253, P = 0.0005). Conclusions: Higher preoperative levels of IL-17A, MCP-1, IFN-γ, E-selectin, and sICAM-1 in the AqH were associated with lower ECD after DSAEK for bullous keratopathy.

Association between corneal endothelial cell densities and elevated cytokine levels in the aqueous humor.

Annual reduction rate of corneal endothelial cell density (ECD) varies among etiologies, however, the cause of chronic endothelial cell loss is still unknown. We recently reported the elevation of inflammatory cytokines in the aqueous humor (AqH) in eyes with bullous keratopathy and low ECD. To evaluate the association between ECD and aqueous cytokine levels, we collected a total of 157 AqH samples prospectively. The AqH levels of cytokines were measured and multivariate analyses were conducted to find the correlation between ECD, aqueous cytokine levels and clinical factors, such as number of previous intraocular surgeries and protein concentration in AqH. As a result, ECD was negatively correlated with specific cytokine levels, including IL-1α, IL-4, IL-13, MIP-1ß, TNF-α and E-selectin (all P < 0.05). The aqueous cytokine levels showed different correlations with these clinical factors; the number of previous intraocular surgeries was associated with all cytokines except MIP-1α. The AqH protein concentration and the status of intraocular lens showed similar patterns of elevation of IL-1α, IL-4, IL-6, IL-8, IL-10, IL-13, IL-17A, MIP-1ß, MCP-1, E-selectin, P-selectin and sICAM-1. In conclusion, elevation of AqH cytokine levels was associated with reduced ECDs. AqH cytokine levels showed significant correlations with clinical factors associated with low ECDs.

Elevated Aqueous Cytokine Levels in Eyes With Ocular Surface Diseases.

PURPOSE: To evaluate cytokine and protein levels in the aqueous humor (AqH) of eyes with ocular surface diseases. DESIGN: Prospective consecutive case series. METHODS: This study includes 14 patients (aged 62.4 ± 13.7 years) with chronic-phase ocular surface diseases (4 with ocular cicatricial pemphigoid, 5 with chemical burns, 2 with a thermal burn, 2 with Stevens-Johnson syndrome, and 1 with exposure keratitis), 14 matched patients without ocular surface disease (controls with corneal scar), and 30 patients who underwent cataract surgery (healthy controls). AqH samples were collected at the beginning of surgery. AqH levels of cytokines (interleukin [IL]-1α, IL-1ß, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17A, monocyte chemotactic protein [MCP]-1, interferon [IFN]-α, IFN-γ, macrophage inflammatory protein [MIP]-1α, MIP-1ß, P-selectin, E-selectin, soluble-intercellular adhesion molecule [s-ICAM]-1, tumor necrosis factor [TNF]-α, granulocyte-macrophage colony-stimulating factor [GM-CSF], IFN-γ-induced protein [IP]-10) were measured using multiplex beads immunoassays. RESULTS: The levels of IL-6, IL-10, IL-17A, GM-CSF, E-selectin, P-selectin, and s-ICAM in AqH were significantly elevated in eyes with ocular surface diseases (in pg/mL: 1696 ± 804, 4.0 ± 1.0, 24.3 ± 9.8, 26.0 ± 18.3, 5150 ± 1232, 13122 ± 7219, and 7914 ± 2813, respectively), compared to healthy controls (IL-6: 6.36 ± 0.94, P = .001; IL-10: 1.68 ± 0.04, P = .0006; IL-17A: 3.7 ± 0.2, P = .008; GM-CSF: 2.7 ± 0.3, P = .007; E-selectin: 2093 ± 37, P = .0001; P-selectin: 3658 ± 137, P = .0001; sICAM-1: 1397 ± 119, P = .008). The levels of IL-6, IL-17A, E-selectin, and P-selectin in AqH were significantly higher in eyes with ocular surface diseases compared to those with corneal scar (IL-6: 44.1 ± 15.0, P = .0077; IL-17A: 4.1 ± 0.7, P = .034; E-selectin: 2439 ± 302, P = .039; and P-selectin: 5673 ± 1553, P = .017). CONCLUSIONS: Multiple AqH cytokine levels were elevated in chronic ocular surface diseases.