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.

The Early Effects of Alcohol Consumption on Functional Visual Acuity, Tear Functions, and the Ocular Surface.

PURPOSE: We investigated the early effects of alcohol intake on tear functions and ocular surface health in this prospective controlled study. METHODS: Forty-four eyes of 22 subjects (17 males, 5 females; mean age: 35.3 years) who drank 200 mL of 25% Japanese vodka and 44 eyes of age- and sex-matched 22 control subjects who drank water were investigated. Subjects were requested to refrain from alcohol consumption from the previous day and food ingestion 6 hr before the study. Each subject consumed exactly the same order prepared dinner and same quantity of alcohol over the same time frame. Subjects underwent breath alcohol level, tear evaporation and blink rate, tear lipid layer interferometry, tear film break-up time (BUT), fluorescein and Rose Bengal stainings, Schirmer test, and visual analog scale (VAS) evaluation of dry eye symptoms before, as well as 2 and 12 hr after alcohol intake. RESULTS: The mean breath alcohol level was significantly higher in the alcohol group compared to the water group at 2 and 12 hr (P<0.001). The mean tear evaporation increased significantly from 2.5×10-7 to 8.8×10-7 gr/cm2/sec 12 hr after alcohol intake (P<0.001). The mean BUT shortened significantly from 15.0±5.0 to 5.0±2.5 sec 12 hr after alcohol intake. Lipid layer interferometry showed signs of tear film thinning 12 hr after alcohol intake in all subjects of the alcohol intake group, which was not observed in the water group. The mean blink rates increased significantly from 10.6±1.5 blinks/min to 13.5±0.9 blinks/min and 15.1±1.2 blinks/min at 2 and 12 hr, respectively, in the alcohol group (P<0.001). The Schirmer test values decreased significantly 12 hr after alcohol intake (P<0.001). The mean VAS score for dryness increased from baseline significantly in the alcohol group at 12 hr (P<0.001). No significant time-wise changes in tear functions were observed in the water group. CONCLUSION: The tear film and ocular surface epithelia showed early and distinctive quantitative and qualitative changes associated with visual disturbances after alcohol intake.

Chemotactic responses of peripheral blood eosinophils to prostaglandin D2 in atopic keratoconjunctivitis.

BACKGROUND: Eosinophils appear to be key cells in the pathogenesis of conjunctival inflammation in atopic keratoconjunctivitis (AKC). Chemoattractant receptor homologous molecule expressed on TH2 cells (CRTH2) mediates prostaglandin D2 (PGD2)-dependent migration of eosinophils. However, it is unclear whether CRTH2/PGD2-dependent eosinophil migration is upregulated in allergic diseases. OBJECTIVE: To compare the chemotactic responses of peripheral blood eosinophils to prostaglandin D2 in patients with severe AKC and healthy individuals. METHODS: We used an enzyme immunoassay system to measure PGD2 levels in tears and blood samples from healthy individuals and patients with AKC. CRTH2 expression on peripheral blood eosinophils was determined using reverse-transcriptase polymerase chain reaction (RT-PCR), flow cytometry, and an oligonucleotide array system. Chemotaxis experiments were performed using a modified Boyden chamber technique and an optical assay system. RESULTS: The PGD2 concentrations were higher in tears from patients with severe AKC compared with healthy individuals. RT-PCR (severe and mild cases), flow cytometry (mild cases), and GeneChip analyses revealed a significantly higher expression of CRTH2 on peripheral blood eosinophils in patients with AKC than in healthy individuals. PGD2 and its stable metabolite 13,14-dihydro-15-keto-PGD2, a CRTH2 agonist, induced chemotaxis of eosinophils from patients with AKC; chemotaxis was significantly enhanced in eosinophils from patients with severe AKC compared with those from healthy individuals. CONCLUSION: CRTH2 is more abundantly expressed on eosinophils from patients with AKC and promoted PGD2-dependent migration to a greater extent than in healthy individuals.

Iris metastasis as the initial presentation of metastatic esophageal cancer diagnosed by fine needle aspiration biopsy: A case report.

RATIONALE: Metastasis of neoplasms to the eye is quite uncommon. In this case report, we describe a patient where primary esophageal cancer was diagnosed by fine needle aspiration biopsy (FNAB) of an iris tumor. PATIENT CONCERNS: A 70-year-old male complained of redness and discomfort in the right eye. DIAGNOSIS AND INTERVENTIONS: The patient's right eye was diagnosed as idiopathic uveitis, and a topical steroid was administered. As vitreous opacities were observed even after topical therapy, oral prednisolone was administered. On slit-lamp examination of the right eye, an iris mass with neovascularization was seen in the anterior chamber. A metastatic tumor was suspected, and FNAB was performed. Histology revealed squamous cell carcinoma. Systemic workup revealed esophageal cancer with several metastases. Best-corrected visual acuity decreased to 20/400, and intraocular pressure was 40 mmHg in the right eye. Two iris tumors with neovascularization were present extending into the anterior chamber with posterior iris synechiae and 360 degree peripheral anterior synechiae. Intraocular pressure in the right eye was medically managed with hypotensive eye drops and oral acetazolamide. Iris metastases were treated with 40 Gray of radiation therapy and concurrent chemotherapy. OUTCOMES: The tumor regressed, but intraocular pressure was refractory to treatment because of 360 degree goniosynechial closure. The right eye lost light perception six months after treatment commenced, and the patient died 9 months after the onset of therapy due to multiple systemic metastases. LESSONS: This is a rare case of masquerade syndrome without systemic symptoms in which FNAB of an iris tumor led to a diagnosis of metastatic esophageal squamous cell carcinoma. Although the patient lost his sight due to uncontrollable ocular hypertension, systemic chemotherapy, and radiation therapy were initially effective in the treatment of the metastatic iris tumor. As the prognosis of patients with metastatic iris tumors is poor, it is important for ophthalmologists to consider such diagnoses and conduct systemic investigations when necessary.

Evaluation of lipid oxidative stress status and inflammation in atopic ocular surface disease.

BACKGROUND: Although the oxidative stress status in atopic skin disease has been reported to be elevated, there are still no studies related to the status of oxidative stress in atopic ocular surface disease. The purpose of this study was to evaluate the ocular surface lipid oxidative stress status and inflammation in atopic keratoconjunctivitis (AKC) patients and normal subjects. METHODS: Twenty eight eyes of 14 patients (9 males, 5 females) with AKC and 18 eyes of 9 age and sex matched (4 males and 5 females) normal healthy controls were examined in this prospective study. The severity of atopic dermatitis (AD) was scored by the SCORing Atopic Dermatitis (SCORAD) index. All subjects underwent Schirmer test, tear film break up time (BUT), fluorescein/Rose Bengal stainings, tear collection, and brush cytology from the upper palpebral conjunctiva. The brush cytology samples were stained with Diff-Quik for differentiation of inflammatory cells and immunohistochemistry (IHC) staining with HEL (hexanoyl-lysine) and 4-HNE (4-hydroxy-2-nonenal) to study lipid oxidation. HEL and cytokine (interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ)) levels were measured by enzyme-linked immunosorbent assay (ELISA) from tear samples of AKC patients and control subjects. Toluidine Blue and IHC staining with HEL, 4-HNE and cluster of differentiation 45 (CD45) were performed on papillary samples of AKC patients. This study was conducted in compliance with the "Declaration of Helsinki." RESULTS: The tear stability and vital staining scores were significantly worse in eyes of AKC patients (p<0.05) compared to the controls. Inflammatory cells and positively stained conjunctival epithelial cells for HEL and 4-HNE showed a significant elevation in brush cytology samples of AKC patients. Significantly higher levels of HEL and cytokines were detected in tears of AKC patients compared to controls. Papillary specimens also revealed many CD45 inflammatory cells as well as many cells positively stained with HEL and 4-HNE in IHC. A strong significant linear positive correlation between conjunctival inflammation and epithelial lipid oxidative stress status was observed. Conjunctival lipid oxidative stress also correlated strongly with tear HEL levels and epithelial damage scores. CONCLUSIONS: The ocular surface disease in AKC was characterized by marked tear instability, ocular surface epithelial damage, increase in inflammatory infiltrates and presence of increased lipid oxidation.

Application of visante optical coherence tomography tear meniscus height measurement in the diagnosis of dry eye disease.

PURPOSE: To investigate the applicability of tear meniscus height (TMH) measurement using Visante optical coherence tomography (OCT) in the diagnosis of dry eye disease. DESIGN: Prospective, controlled, single-center study. PARTICIPANTS: Twenty-four right eyes of 24 patients (6 males, 18 females; mean age, 63.14±13.4 years) with definite dry eye according to the Japanese dry eye diagnostic criteria and 27 right eyes of 27 control subjects (12 males, 15 females; mean age, 56.04±14.22 years) were recruited. METHODS: All subjects underwent slit-lamp TMH measurement, OCT upper and lower TMH measurements, tear film breakup time (BUT) measurements, vital stainings, and Schirmer test. The results were compared between the 2 groups by Mann-Whitney test. MAIN OUTCOME MEASURES: The correlation between the clinical findings of slit-lamp TMH, strip meniscometry examination, tear functions, vital staining scores, and the OCT upper and lower TMH parameters were tested by Spearman's correlation test. Receiver operating characteristic (ROC) curve technique was used to evaluate the sensitivity, specificity and cutoff values of OCT TMH examination in the diagnosis of dry eye. RESULTS: The OCT upper and lower TMH values, slit-lamp TMH, strip meniscometry, tear film BUT, and vital staining scores were significantly lower in the dry eye patients compared with controls (P<0.001). A significant correlation between the OCT upper and lower TMH measurements as well as slit-lamp TMH, strip meniscometry, tear functions, vital staining scores, and the Schirmer test was found. The ROC curve technique analysis of the OCT lower TMH showed that, when the cutoff value was set at <0.30 mm, the sensitivity and specificity of the testing were 67% and 81%, respectively. CONCLUSIONS: The Visante OCT is a quick, noninvasive method for assessing the TMH, with acceptable sensitivity, specificity, and repeatability, and may have potential applications for the diagnosis and evaluation of dry eye disease.

Mucosal lesions may be a minor complication of SAPHO syndrome: a study of 11 Japanese patients with SAPHO syndrome.

Since the term synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) syndrome was proposed by Chamot et al. (Rev Rhum Mal Osteoartic 54:187-196, 1987), clinical reviews concerning this syndrome have been mainly reported from Europe. We carried out a retrospective analysis of 11 Japanese patients with SAPHO syndrome, and reviewed the clinical features of our series in comparison with those in a European large case study. In this study the major features of SAPHO syndrome were chronic osteitis of the anterior chest wall and pustulotic arthro-ostitis with middle age onset, and mucosal lesions seemed to be a minor complication of SAPHO syndrome. The non-erosive peripheral large joints arthritis and the particular HLA types (HLA-B51, B52, or A26), which had been reported to be increased in Behcet's disease, were frequently seen in SAPHO syndrome with mucosal lesions. This study also suggests that SAPHO syndrome with mucosal lesions may be part of a broader disease spectrum including Behcet's disease.

Corneal and conjunctival fibroblasts are major sources of eosinophil-recruiting chemokines.

BACKGROUND: Differential expression of chemokine genes were investigated in various types of ocular surface cells. METHODS: Primary cultures of human corneal epithelial cells (n = 3), corneal fibroblasts (n = 2), conjunctival epithelial cells (n = 2) and conjunctival fibroblasts (n = 2) were established and incubated with or without interleukin (IL)-4 (30ng/ml) and tumor necrosis factor (TNF)-alpha(30ng/ml) for 24 hours. Gene transcription levels of 33 chemokines and production of 4 chemokines were analyzed. RESULTS: After stimulation, chemokine expression increased for 18 of 33 coded chemokine gene transcripts. In stimulated conjunctival and corneal cells, CC chemokine genes increased in fibroblasts (expression of 6 out of 8 genes), while CXC chemokine genes increased in both epithelial cells (expression of 4 out of 9 genes in conjunctival epithelial cells and 7 out of 9 genes in corneal epithelial cells) and in fibroblasts (expression of 8 out of 9 genes in conjunctival and corneal fibroblasts). Except for MCP-1, gene transcription levels for most CC chemokines were inducible and, except for IP-10 and I-TAC, most CXC chemokines were constitutively expressed. Corneal epithelial cell and fibroblast production patterns for eotaxin-1, MCP-1 and IP-10 were comparable to the mRNA expression pattern. CONCLUSIONS: Corneal and conjunctival fibroblasts exhibited marked increases in the expression of chemokines upon stimulation with TNF-alpha and IL-4, suggesting that fibroblasts may be one of the primary sources of chemokines in allergic conjunctival diseases. Therefore, regulation of chemokine production from these cells may be an effective strategy for treating such diseases.

Suppressive effects of tranilast on eotaxin-1 production from cultured conjunctival fibroblasts.

PURPOSE: Eotaxin, a CC-chemokine with selective chemotactic effects for eosinophils, has been reported to play an important role in allergic conjunctival diseases. We previously reported that eotaxin is produced by conjunctival fibroblasts and keratocytes on stimulation with Th2 cytokines. Tranilast is known to have anti-allergic properties. In this study, we examined the inhibitory effect of tranilast, an anti-allergic drug, on eotaxin-1 production from cultured conjunctival fibroblasts. METHODS: Conjunctival fibroblasts obtained from normal patients were cultured in DMEM/F12 medium. On the fifth passage, the cells were transferred to a 96-well plate and, after starvation for 24 hr, TNF-alpha, IL-4, and tranilast or dexamethasone were added. After 48 hr, the concentrations of eotaxin-1 in the supernatants were measured by ELISA, and the cells were tested for eotaxin-1 expression by real-time PCR. RESULTS: Eotaxin-1 production was observed on simultaneous stimulation with TNF-alpha and IL-4. This production was inhibited by both tranilast and dexamethasone. Inhibition of eotaxin-1 expression was also observed by real-time PCR. CONCLUSIONS: Eotaxin-1 production from conjunctival fibroblasts was inhibited by both tranilast and dexamethasone. These results suggest that the anti-allergic effect of tranilast may be partly due to the inhibition of eotaxin-1 production from conjunctival fibroblasts.

Two cases of SAPHO syndrome accompanied by classic features of Behcet's disease and review of the literature.

We describe two patients with SAPHO (synovitis-acne-pustulosis-hyperostosis-ostitis) syndrome who presented some of the classic features of Behcet's disease. The first case is a man diagnosed as SAPHO at 74 years old. His major complaint is pain and swelling of the bilateral sterno-clavicular region for more than 14 years. Another conspicuous complication was bilateral glaucoma and episodes of iritis were recognized during the follow-up period. The second case is a 65-year-old woman, who first consulted us with right knee pain. As she had a past history of palmoplantar pustulosis and anterior chest pain, her sterile knee arthritis was diagnosed as SAPHO. She also had been suffering from recurrent oral aphthous ulceration since 6 months before visiting our hospital. Considering the clinical courses of our two cases and a review of five previously reported cases, these conditions may imply that classic features of Behcet's disease are minor complications of SAPHO syndrome. Human leukocyte antigen typing and frequent association of sacroiliitis in our cases and in the review of the literature for SAPHO syndrome with some of the classic features of Behcet's disease may indicate this condition to be a closely related disease with seronegative spondylo-arthritis.

Objective Ocular Discomfort: Noninvasive Evaluation by Functional Near-Infrared Ray Spectroscopy.

Purpose: Patients express their discomfort by subjective complaints, which may not clearly express the extent of their discomfort. This study noninvasively and objectively quantified ocular discomfort, a form of feeling, from the prefrontal cortex by functional near-infrared ray spectroscopy topography. Methods: This case-controlled study enrolled six dry eye patients (male:female, 1:1; 51.8 ± 15.9 years) with ocular discomfort and six normal controls (male:female, 1:1; 48.8 ± 15.2 years). Ocular discomfort was created by Schirmer 1 test in normal controls. The extent of prefrontal cortex activity was evaluated as the number of signal-positive channels using the system by using an eye-opening task with spontaneous blinking in the dark. Changes in the signal-positive channels count by lubricant or anesthetics instillation were analyzed. Results: Low prefrontal cortex activation was detected in normal controls without ocular discomfort, and high activation was detected in both normal controls and dry eye with ocular discomfort. Prefrontal cortex activity was confirmed with ocular discomfort when the eyes were open, decreased with lubricant, and almost disappeared with anesthetic for all participants. Conclusions: These changes in the prefrontal cortex activity exhibited a significant correlation to subjective complaint scores, suggesting that such discomfort may be objectively quantifiable, independent of subjective expressions.

Tear protein analysis in presumed congenital alacrima.

OBJECTIVES: It is often hard to reach a definitive diagnosis of congenital alacrima because of the difficultly in proving the lack of lacrimal tissue. We report here the distinct tear protein profile in presumed congenital alacrima. PATIENTS AND METHODS: A 13-year-old girl with presumed congenital alacrima and 15 healthy volunteers aged 23-35 years were included in this study. Tears were collected using Schirmer strips, and tear protein analyses were performed. Tear samples were collected from the patient with alacrima before and after surgical punctal occlusion of both the upper and lower puncta, and tear protein extract was fractionated using HPLC. Lactoferrin and albumin concentrations in the tears were separately determined using ELISA. RESULTS: The chromatogram in the patient greatly differed from that in normal subjects with low concentrations of secretory IgA, lipocalin-1, and lysozyme. ELISA results indicated that the tear fluid in the patient contained a high concentration of albumin but a minimal concentration of lactoferrin. Punctal occlusion improved the ocular surface findings, but major lacrimal protein concentrations remained low and tear albumin concentrations further increased. CONCLUSION: The tear protein profile of a patient with presumed congenital alacrima greatly differed from that of normal subjects. Tear protein analysis may be useful in making a diagnosis of congenital alacrima and in assessing the efficacy and mechanism of punctal occlusion.

Conjunctival in vivo confocal scanning laser microscopy in patients with atopic keratoconjunctivitis.

PURPOSE: To elucidate the morphological alterations of the conjunctiva in atopic keratoconjunctivitis (AKC) using the new generation Heidelberg Retina Tomograph II (HRT II)/Rostock Cornea Module confocal microscope in a prospective controlled study. METHODS: Sixteen eyes from AKC patients (eight males, mean age: 20.3+/-5.9 years) were treated with 0.05% topical cyclosporine A (CsA) in addition to topical steroid and anti-allergic eye drops and 12 eyes from patients with AKC were treated using topical steroids and anti-allergic drops (six males, mean age: 22.2+/-10.0 year). These two groups, as well as 14 eyes from normal subjects (six males, one female, average age 30.4+/-6.8 years) were studied. All subjects underwent corneal sensitivity measurements, the Schirmer test, tear film break-up time (BUT), fluorescein, Rose Bengal staining of the ocular surface, and confocal laser scanning microscopy of the tarsal palpebral conjunctiva. The density of conjunctival inflammatory infiltrates was calculated. Morphological characteristics of the papillary lesions were also studied. RESULTS: Corneal sensitivity, tear stability, and vital staining scores were significantly worse in patients with AKC compared to control subjects (p<0.01). Eyes of AKC patients using CsA showed a significantly lower density of inflammatory infiltrates compared to eyes on topical steroid and anti-allergic drops. Conjunctival inflammatory cell density showed a negative correlation with tear stability and corneal sensitivity and a positive correlation with the vital staining scores. Papillary lesions revealed remarkable fibrosis in patients using CsA. CONCLUSIONS: Confocal scanning laser microscopy was an efficient and a noninvasive tool for the quantitative assessment of the conjunctival inflammation and evaluation of pathological alterations in the papillary lesions and their relation to the ocular surface disease in patients with AKC.

Long-standing bullous keratopathy is associated with peripheral conjunctivalization and limbal deficiency.

OBJECTIVE: To investigate whether peripheral corneal neovascularization in bullous keratopathy (BK) is due to conjunctivalization, a sign of limbal stem cell deficiency. DESIGN: Observational case-control study. PARTICIPANTS: Sixteen BK patients. METHODS: Patients were divided into 2 groups: BK without peripheral neovascularization [NV(-) group; 5 patients, 5 eyes] and BK with neovascularization [NV(+) group; 11 patients, 13 eyes]. Evidence of conjunctivalization was evaluated by periodic acid-Schiff staining of impression cytology samples from the peripheral vascularized cornea. The 2 groups' durations of disease also were compared. Penetrating keratoplasty (PK) was performed in all 16 cases, and the 2 groups' durations of reepithelialization after PK were compared. MAIN OUTCOME MEASURES: Presence of goblet cells using impression cytology, duration of BK, and duration of postoperative reepithelialization. RESULTS: Goblet cells were found on the peripheral corneal surface in all eyes in the NV(+) group. However, all eyes in the NV(-) group were negative for goblet cells (P<0.0001). Duration of disease was 14.4+/-5.4 months in the NV(-) group and 66.2+/-65.5 months in the NV(+) group (P = 0.030). Duration of postoperative epithelialization was 6.2+/-2.2 days in the NV(-) group and 28.8+/-36.5 days in the NV(+) group (P = 0.046). CONCLUSION: Conjunctivalization of the peripheral cornea and delayed postoperative epithelialization in BK patients with NV suggest the presence of limbal stem cell deficiency in such patients. Patients with long-standing disease were found to be more prone to neovascularization. For this reason, early surgery may lead to a better surgical outcome.

The impact of the onset time of atopic keratoconjunctivitis on the tear function and ocular surface findings.

PURPOSE: To investigate the tear and ocular surface findings between controls, children, and adults with atopic keratoconjunctivitis (AKC). DESIGN: Prospective comparative study. METHODS: Twenty eyes of 10 childhood-onset, 10 eyes of five adult-onset, AKC adult patients, and 12 eyes of six children with infantile-onset AKC, 14 eyes of seven normal adults and seven normal children were recruited. Corneal aesthesiometry, Schirmer test, tear film break-up time (BUT), vital staining, and conjunctival impression cytology were performed. RESULTS: The Schirmer and Rose Bengal scores in childhood-onset adult AKC patients were considerably worse than adult-onset adult AKC patients, pediatric subjects, and the controls (P < .05). The same significant relation was observed in impression cytology parameters. CONCLUSIONS: Ocular surface disease in childhood-onset adult AKC patients was characterized by greater ocular surface epithelial damage. Prolonged inflammation may be important in the evolution and progression of ocular surface disease in patients with longstanding active AKC.

Quantitative evaluation of the early changes in ocular surface inflammation following MMC-aided papillary resection in severe allergic patients with corneal complications.

BACKGROUND: Atopic keratoconjunctivitis (AKC) and vernal keratoconjunctivitis (VKC) are chronic inflammatory allergic diseases that are associated with some common conjunctival and corneal complications.1 The clinical corneal manifestations of both entities may include superficial punctate keratitis, macroerosions, corneal ulceration, plaque formation, corneal neovascularization, and lipid infiltration. PURPOSE: To quantitatively evaluate the early ocular surface inflammation before and after mitomycin C (MMC)-aided papillary resection in severe allergy patients with corneal complications. METHODS: Three eyes with VKC and 5 eyes with AKC were included in this study. All eyes had cobblestone-like papillae on the upper tarsal conjunctiva and corneal complications such as corneal ulcers, defect, or erosions that were refractory to conventional treatment of more than 2 weeks. Papillary resection with intraoperative 0.05% MMC application for 5 minutes on the palpebral conjunctiva was carried out in all eyes. Corneal and conjunctival findings were evaluated before and 1 week and 2 weeks after surgery. Brush cytology (BC) and evaluation of tear eosinophilic cationic protein (ECP) levels by radioimmunoassay techniques were performed as well pre- and postoperatively. RESULTS: Corneal and conjunctival complications resolved in all patients within 7 days after resection. Postoperative tear ECP levels decreased significantly with papillary resection (P< 0.05). Concomitant brush cytology showed a significant decrease in the number of eosinophils and neutrophils following papillary resection (P < 0.05). CONCLUSION: MMC-aided papillary resection provided a dramatic decrease in ocular surface inflammation as evidenced by decrease in the number of inflammatory cells as well as tear ECP levels with a rapid improvement of clinical corneal and conjunctival findings.

Abnormal Corneal Lesions Induced by Trastuzumab Emtansine: An Antibody-Drug Conjugate for Breast Cancer.

PURPOSE: To report a case of atypical corneal lesions presumably induced by trastuzumab emtansine, an antibody-drug conjugate that is designed to selectively deliver cytotoxic agents to human epidermal growth factor receptor 2 (HER2)-positive breast cancer cells. CASE: A 64-year-old Japanese woman developed bilateral corneal epithelial abnormalities that originated from the limbus. The corneal lesions covered the superior area in the right eye and both superior and inferior areas including the visual axis in the left eye. The patient had advanced ductal carcinoma of the left breast and had been receiving anticancer treatment with trastuzumab emtansine for 15 months. After switching the chemotherapy from trastuzumab emtansine monotherapy to the combination of docetaxel, trastuzumab, and pertuzumab, the abnormal corneal lesions showed gradual improvement. CONCLUSIONS: As corneal epithelial cells express human epidermal growth factor receptor 2 under normal conditions, such cells may also be targeted by trastuzumab emtansine and lead to corneal epithelial lesions.

The implications of the upregulation of ICAM-1/VCAM-1 expression of corneal fibroblasts on the pathogenesis of allergic keratopathy.

OBJECTIVE: The present study investigated the expression of ICAM-1 and VCAM-1 on fibroblasts with interleukin (IL)-4 and/or tumor necrosis factor (TNF)-alpha stimulation and assessed the effect of eosinophil adhesion on fibroblast viability. METHODS: Primary cultured human corneal fibroblasts were incubated with IL-4, TNF-alpha, or their combination for 24 hours. Expression of ICAM-1 and VCAM-1 was examined by real-time quantitative PCR and flow cytometric analysis. Purified eosinophils were cocultured with activated fibroblasts, and the number of eosinophils adhered to fibroblasts and the number of damaged fibroblasts were counted using microscopy. In a separate trial, conjunctival and corneal impression cytology was performed on patients with atopic keratoconjunctivitis and corneal ulcers (eight eyes) to assess the status of the ocular surface epithelium and the presence of inflammatory cell infiltrates. RESULTS: Real-time quantitative PCR and flow cytometric analysis revealed that both mRNA and protein of VCAM-1 and ICAM-1 were upregulated by IL-4 and TNF-alpha. IL-5-primed eosinophils adhered to the corneal fibroblasts treated with IL-4 and TNF-alpha, and the fibroblasts were damaged by eosinophil adherence. Anti-ICAM-1 antibody and anti-VCAM-1 antibody inhibited the eosinophil adherence to fibroblasts and the fibroblast damage. Impression cytology revealed extensive infiltration of neutrophil and eosinophils among isolated ocular surface epithelial cells with advanced squamous metaplasia. CONCLUSIONS: Corneal fibroblasts expressed ICAM-1 and VCAM-1 when activated with IL-4 and TNF-alpha. Eosinophils can adhere to the activated fibroblasts and can induce subsequent fibroblast damage through these adhesion molecules. Eosinophil adhesion to fibroblasts may possibly contribute to the pathogenesis of severe persistent allergic corneal ulcers.

Clinical evaluation of the accuracy of intraocular pressure measurement by Tono-Pen XL in eyes with amniotic membrane patching.

PURPOSE: To evaluate the influence of amniotic membrane on intraocular pressure (IOP) measurement with the Tono-Pen. DESIGN: Observational case series. METHOD: Eight patients with partial limbal dysfunction who underwent penetrating keratoplasty were recruited. Amniotic membranes were patched just after keratoplasty. One week postoperatively, amniotic membranes were removed, and accuracy of IOP measurement with the Tono-Pen was evaluated with comparisons before and after the removal. RESULTS: No epithelial defects were detected after the removal of amniotic membrane. Mean IOPs with and without amniotic membranes were 16.6 +/- 3.0 mm Hg (mean +/- SD) and 16.0 +/- 3.7 mm Hg, respectively. The difference was not statistically significant. CONCLUSIONS: Assessment of IOP with the Tono-Pen was observed to be accurate even when used over an amniotic membranes patch in cases who underwent penetrating keratoplasty.

Pupil decentration and iris tilting detected by Orbscan: anatomic variations among healthy subjects and influence on outcomes of laser refractive surgeries.

PURPOSE: To investigate the anatomic variations of entrance pupil decentration and tilting angle of the iris in healthy subjects and the influence of these factors on the outcome of laser in situ keratomileusis (LASIK). SETTING: Minamiaoyama Eye Clinic, Tokyo, Japan. METHODS: The degree of pupil decentration and tilting angle of the iris in 2280 eyes of 1144 myopic patients without abnormal findings by ophthalmologic examination were assessed using Orbscan. Of these, 901 eyes of 467 patients had LASIK. Multiple analysis of variance (ANOVA) was used to determine risk factors for reduction of postoperative best spectacle-corrected visual acuity (BSCVA) considering patient age, refractive power, tilting angle of the iris, pupil decentration, and corneal power. RESULTS: The mean pupil decentration in all eyes was 0.19 mm +/- 0.11 (SD) (range 0 to 0.9 mm); tilting angle of the iris was 4.06 +/- 1.41 degrees (range 0.19 to 12.69 degrees). By multiple ANOVA, refractive power, pupil decentration, and tilting angle of the iris were significant for the reduction of BSCVA. CONCLUSIONS: Some eyes with pupil decentration or tilting angle of the iris could not be detected under typical ophthalmologic examination but only with topographic examination. Attention should be paid to eyes with large pupil decentration and tilting angle of the iris because these may be risk factors for reduction of postoperative BSCVA during corneal refractive surgeries.