Published papers

Purpose. To prospectively evaluate the effect of controlled adverse chamber environment (CACE) exposure on tear function, including tear osmolarity, in subjects wearing narafilcon A versus those wearing etafilcon A soft contact lens (SCL). Methods. Thirty-one healthy subjects with no history of contact lens wear (13 women, 18 men; average age, 30.5 ± 6.5 years) were randomly divided into age- and sex-matched groups (15 subjects wearing narafilcon A SCL; 16 subjects wearing etafilcon A SCL) and entered a CACE for 20 minutes. All subjects underwent tear osmolarity, tear evaporation rate, strip meniscometry, tear film breakup time, fluorescein vital staining, and functional visual acuity measurement before and after exposure to the controlled adverse chamber. Results. The mean blink rate increased with significant deteriorations in the mean symptom VAS scores, mean tear osmolarity, tear evaporation rate, strip meniscometry score, and tear stability with CACE exposure along with a decrease in visual maintenance ratio in functional visual acuity testing in etafilcon A wearers. The mean symptom VAS scores, mean tear evaporation rate, tear stability, blink rates, and visual maintenance ratios did not change significantly in narafilcon A wearers after CACE exposure. Conclusions. This study suggested marked tear instability, higher tear osmolarity, and increased tear evaporation with marked dry eye and visual symptomatology in nonadapted hydrogel SCL wearers, suggesting that silicone hydrogel SCLs may be suitable for persons who live and work in cool, low-humidity, and windy environments, as tested in this study. © 2011 The Association for Research in Vision and Ophthalmology, Inc.

Purpose. AMP-activated protein kinase (AMPK) is a sensor of cellular energy status. The purpose of the present study was to elucidate the roles of AMPK in the pathogenesis of diabetic retinopathy using the known AMPK activators resveratrol and AICAR (5-aminoimidazole-4-carboxamide ribonucleoside) in a mouse model. Methods. C57BL/6 mice with streptozotocin-induced diabetes were treated with resveratrol orally at 50 mg/kg for 7 days or with AICAR intraperitoneally at 100 mg/kg 24 hours before death. Retinal protein levels of phosphorylated and total AMPK, phosphorylated nuclear factor (NF)-κB p65, intercellular adhesion molecule (ICAM)-1, and vascular endothelial growth factor (VEGF) were evaluated by Western blot analysis or enzyme-linked immunosorbent assay. Retinal activity of sirtuin (SIRT)1 was measured by deacetylase fluorometric assay. Leukocyte adhesion to the retinal vasculature was examined with a concanavalin A lectin perfusion-labeling technique. Results. Induction of diabetes in mice led to retinal AMPK dephosphorylation, which was significantly reversed by either resveratrol or AICAR. Either resveratrol or AICAR significantly reversed SIRT1 deactivation and NF-κB phosphorylation, both of which were induced in the diabetic retina. Administration of resveratrol to diabetic mice significantly reduced diabetes-induced retinal leukocyte adhesion, together with retinal expression of ICAM-1 and VEGF. Conclusions. The present findings reveal that diabetes-induced retinal inflammation stems from downregulation of the AMPK pathway, leading subsequently to SIRT1 deactivation and NF-κB activation. The data also suggest the potential use of the AMPK activator resveratrol as a therapeutic agent for diabetic retinopathy. © 2011 The Association for Research in Vision and Ophthalmology, Inc.

Purpose. To characterize corneal epithelial cells separated from limbus in vivo by transplantation of a stainless steel ring with or without creating a defect inside the ring. Methods. A stainless steel ring (diameter, 8 mm; width, 300 μm; depth, 250 μm) was transplanted into rabbit corneal stroma using 10-0 nylon interrupted suture after cutting to a 250 μm depth by corneal vacuum trephine (diameter, 8.0 mm). Epithelial cells were removed inside the ring, and re-epithelization was evaluated after 1 week. Hematoxylin staining and immunostaining against p63, Ki67, and cytokeratin 3 were performed for phenotypic analysis of corneal epithelia. A corneal epithelial defect was centrally created inside the ring (4, 5, and 6 mm diameter) after transplantation. When re-epithelization was achieved, a central epithelial defect was continuously created until cells were exhausted within the ring. The number of created defects was also analyzed to assess the potential of re-epithelialization. Results. Ring-transplanted corneal stroma showed few signs of inflammation, and when epithelium was totally removed from inside the ring, complete epithelial defects were persistent for ≥ 1 month. Corneal sensation was significantly decreased in corneas with the ring (P < 0.05). Immunostaining demonstrated similar expression patterns for p63, Ki67, and cytokeratin3 as the controls. When rings were transplanted into the intact cornea, inside epithelia prevented epithelial defects in vivo for ≤ 6 months. Conclusions. Transient-amplifying cells might maintain homeostasis for >1 month when separated from their limbus in vivo. This model will be useful for future stem cell research or wound healing models. © 2011 The Association for Research in Vision and Ophthalmology, Inc.

Purpose. To devise a mathematical disease classification model for eyes with primary guttata cornea, on the bases of endothelial loss trajectory and probability of advanced disease. Methods. A series of 1971 patients (3281 eyes), some with and some without guttata corneas, undergoing specular microscopy were retrospectively reviewed. The eyes were classified into four stages; stage 0, without guttae; 1, guttata cornea without edema; 2, mild Fuchs' corneal dystrophy (FCD); and 3, severe FCD, according to clinical records, and patient age and corneal endothelial cell density (ECD) were plotted. Nonparametric density smoothing was used to create a contour map, and a best-fit curve for ECD loss was calculated. The relation between ECD decrease rate and the stages were evaluated. Results. Endothelial decrease rate in stage 0 was 0.44%/year, which was compatible with that of normal eyes reported in previous studies. Decrease rates of stages 1, 2, and 3 were 0.81%, 2.65%, and 3.08%/ year, respectively. The age-ECD loss curves of 1.40%/year (ECO 1.4) and 2.00%/year (ECO 2.0) further divided stage 1 into three subgroups; stage 1a, asymptomatic guttata cornea; 1b, borderline guttata cornea; and 1c, pre-FCD. The ECO 2.0 cutoff line differentiated eyes with FCD from those without edema with a sensitivity and specificity of >90%. Stage 1c eyes were below ECO 2.0 and had a decrease rate as high as FCD. Conclusions. This mathematical model can be used to predict the prognosis of patients with primary guttata cornea. © 2011 The Association for Research in Vision and Ophthalmology, Inc.

Rapid growth in the number of dry eye syndrome patients has been observed worldwide. Increased life span is considered to be at least part of the reason for this because there is a close association between aging and decreased secretory function in the lacrimal gland. Recent advances have led to a new way of thinking about intervention in the aging process. Calorie restriction (CR) is believed to retard functional decline in various organs with age. We hypothesized that CR could prevent age-related lacrimal dysfunction. In this paper, we begin by reviewing the epidemiology of dry eye syndrome and explaining how aging affects lacrimal gland function. We then introduce a possible therapeutic approach to this problem, intervention by means of CR. Finally, suggestions are made for further prospective research that would elucidate the molecular mechanisms by which CR maintains lacrimal gland function. © 2011 by Lippincott Williams & Wilkins.

Aim: To compare and evaluate the efficacy of topical 0.1% micafungin (MCFG) and topical 0.2% fluconazole (FCZ) in the treatment of Candida fungal keratitis. Methods: Twenty-nine eyes of 29 patients who were diagnosed as having Candida fungal keratitis, proven by corneal culture isolates, were investigated in this prospective study. Patients were divided into a MCFG treatment group (12 eyes) and an FCZ treatment group (17 eyes). Age, gender, initial status of ulcer (ulcer size and degree of injection), initial and final best-corrected visual acuity (BCVA), healing periods, final status of cornea and recurrences in each group were studied and compared. Results: There were no significant differences in relation to age, gender, ulcer size and degree of injection before treatment between the two groups. There were also no significant differences in the healing periods until complete epithelialisation (MCFG treatment group (41.3±38.0 days); FCZ treatment group (34.4±37.7 days)), change in BCVA, corneal clarity/ opacification, perforation and recurrence status at the final examination between the two groups. Conclusion: The efficacy of 0.1% MCFG eye-drops appears to be comparable with that of 0.2% FCZ eye-drops in the treatment of Candida fungal keratitis.

Introduction: In this study, we investigated possible aberrations of monocytes from patients with primary Sjogren's syndrome (pSS). We focused on BAFF (B cell activating factor of the TNF family) and IL-6, because they are both produced by monocytes and known to be involved in the pathogenesis of pSS. Methods: Peripheral monocytes were prepared from both pSS patients and normal individuals. The cells were stimulated in vitro with IFN-gamma, and the amounts of IL-6 and sBAFF produced by the cells were quantitated. The effect of sBAFF itself on the production of IL-6 was also studied. To investigate the response of pSS monocytes to these stimuli, the expression levels of the genes encoding BAFF receptors and IL-6-regulating transcription factors were quantitated. Results: Peripheral pSS monocytes produced significantly higher amounts of sBAFF and IL-6 compared to normal monocytes, even in the absence of stimulation. The production of these cytokines was significantly increased upon stimulation with IFN-gamma. The elevated production of IL-6 was significantly suppressed by an anti-BAFF antibody. In addition, stimulation of pSS monocytes with sBAFF induced a significant increase in IL-6 production. Moreover, the expression levels of a BAFF receptor and transcription factors regulating IL-6 were significantly elevated in pSS monocytes compared to normal monocytes. Conclusions: The present study suggests that the mechanisms for the production of sBAFF and IL-6 are impaired in pSS monocytes. Our research implies that this impairment is ascribed to abnormally overexpressed IL-6-regulating transcription factors and a BAFF receptor. These abnormalities may underlie the development of pSS.

Purpose: To report acute angle-closure glaucoma in an eye with cicatricial retinopathy of prematurity and in another with persistent hyperplastic primary vitreous (PHPV). Cases: One was a 28-year-old female with PHPV in both eyes. Her right eye developed acute angle-closure glaucoma with intraocular pressure (IOP) of 48 mmHg. The chamber angle was closed in all the circumference. Lens extraction resulted in increased anterior chamber depth with decreased IOP. The other case was a 20-year-old male with cicatricial retinopathy of prematurity. He had received peripheral iridectomy in the right eye due to elevated IOP at the age of 14. IOP in the right eye rose to 34 mmHg after anterior dislocation of the lens. Lens extraction induced increased anterior chamber depth with decreased IOP. Conclusion: These cases illustrate that lens extraction may be effective for pupillary block after laser iridotomy or peripheral iridectomy has failed.

Purpose: To investigate the relation of functional visual acuity (FVA) measurements with dry eye test parameters and to compare the testing methods with and without blink suppression and anesthetic instillation. Design: A prospective comparative case series. Methods: Thirty right eyes of 30 dry eye patients and 25 right eyes of 25 normal subjects seen at Keio University School of Medicine, Department of Ophthalmology were studied. FVA testing was performed using a FVA measurement system with two different approaches, one in which measurements were made under natural blinking conditions without topical anesthesia (FVA-N) and the other in which the measurements were made under the blink suppression condition with topical anesthetic eye drops (FVA-BS). Tear function examinations, such as the Schirmer test, tear film break-up time, and fluorescein and Rose Bengal vital staining as ocular surface evaluation, were performed. Results: The mean logMAR FVA-N scores and logMAR Landolt visual acuity scores were significantly lower in the dry eye subjects than in the healthy controls (p < 0.05), while there were no statistical differences between the logMAR FVA-BS scores of the dry eye subjects and those of the healthy controls. There was a significant correlation between the logMAR Landolt visual acuities and the logMAR FVA-N and logMAR FVA-BS scores. The FVA-N scores correlated significantly with tear quantities, tear stability and, especially, the ocular surface vital staining scores. Conclusions: FVA measurements performed under natural blinking significantly reflected the tear functions and ocular surface status of the eye and would appear to be a reliable method of FVA testing. FVA measurement is also an accurate predictor of dry eye status. © 2011 Japanese Ophthalmological Society.

We previously reported a high incidence of kerato-conjunctivitis in patients receiving high-dose cytarabine following total body irradiation (TBI) as a conditioning for hematopoietic stem cell transplantation (HSCT) even on prophylaxis with topical corticosteroid. This study aimed to evaluate whether addition of eye rinse, which was designed to remove cytarabine from ocular surface, further reduces the incidence of kerato-conjunctivitis in the same setting. Seventy-six patients receiving cytarabine at a dose of 3 g/m 2 every 12 h for 4 days after receiving TBI (12 Gy) as conditioning for HSCT were evaluated. All patients received betamethasone sodium phosphate eye drops. Twenty-three patients were further instructed to rinse their eyes with sterile saline every 10-15 min during and for two additional hours after the completion of each cytarabine infusion. Among 23 patients with eye rinse, Grades 2-3 and 1-3 kerato-conjunctivitis were observed in 4 (17.4%) and 5 patients (21.7%), respectively. These incidences were significantly lower than those [35 (66.0%) and 41 (77.4%)] observed in 53 patients without eye rinse (P<0.001 and P<0.00001, respectively). These results strongly suggest that eye rinse effectively reduces the incidence and severity of cytarabine-induced kerato-conjunctivitis in HSCT recipients who receive high-dose cytarabine following TBI.

Purpose.: To evaluate the efficacy of surgical treatment for conjunctivochalasis using the Tear Film Stability Analysis System. Methods.: Fifteen eyes of 15 patients (74.5 ± 4.8 years; 14 females and 1 male) who had surgical reconstruction of the tear meniscus for conjunctivochalasis underwent evaluation with a symptom questionnaire, Schirmer I test, fluorescein tear film break-up time (FBUT), and break-up time index (BUI) measurement by Tear Film Stability Analysis System examinations that were performed preoperatively and 3 months after the surgery. Changes of these tear parameters were statistically analyzed using the paired t test. Results.: After the surgery, the mean FBUT and BUI values significantly improved from 5.7 ± 3.2 s and 42.8 ± 18.7, respectively, to 8.4 ± 2.5 s and 60.7 ± 16.5, respectively (FBUT, p = 0.0438; BUI, p = 0.0036). The mean Schirmer test value showed no significant changes before and after surgery (p = 0.9064). Fourteen eyes (93.3%) had improvement of ocular symptoms after surgery. One eye (6.7%) with no improvement of ocular symptoms, FBUT, and BUI after surgery appeared to have aqueous tear deficiency. Conclusions.: Surgical treatment for conjunctivochalasis was associated with improvement of tear stability and clinical dry eye symptoms. Copyright © 2011 American Academy of Optometry.

Purpose: To evaluate the morphological changes of the meibomian glands (MGs) using in vivo laser confocal microscopy (CM) in dry eye (DE) patients with chronic graft-versus-host disease (cGVHD). Methods: Seventeen eyes from 9 patients with a diagnosis of DE associated with cGVHD (DE/cGVHD group; 6 males, 3 females; median 50.5 years) and 16 eyes of 8 hematopoietic stem cell transplantation (HSCT) recipients without DE (non-DE/non-cGVHD group; 5 males, 3 females; median 47.0 years) were enrolled. CM was used to investigate the MG and MG acinar unit density (MGAUD), MG acinar longest diameter (MGALD), MG acinar shortest diameter (MGASD), and the fibrosis grade. Clinical findings of the lid margin were obtained. Tear dynamics, ocular surface vital staining, meibography, and MG expressibility were also examined. Data were compared between the 2 groups using the unpaired t and Mann-Whitney tests. Results: The mean MGAUD value was significantly lower in the DE/cGVHD group than in the non-DE/non-cGVHD group (p=0.01, 57.8±38.3 glands/mm 2, 88.8±26.6 glands/mm 2, respectively), and the mean MGALD and MGASD were significantly shorter in the DE/cGVHD group than in the non-DE/non-cGVHD group (p=0.0018, 37.3±24.4 μm and 60.4±11.8 μm, p=0.0106, 17.7±11.8 μm and 26.6±6.03 μm, respectively). The mean fibrosis grade was significantly higher in the DE/cGVHD group than the non-DE/non-cGVHD group (p<0.0001, 1.39±0.71 grade, 0.06±0.25 grade, respectively). Clinical findings in the lid margin, tear dynamics, and ocular surface findings were significantly worse in the DE/cGVHD group than in the non-DE/non-cGVHD group. Conclusions: CM clearly depicted the morphological changes of the MG in the DE/cGVHD group, and revealed the severity of the meibomian gland dysfunction. Patients with severe DE after HSCT showed atrophic MG and excessive fibrosis. © 2011 Molecular Vision.

Purpose: To investigate the effect of desiccation on secretion of inflammatory cytokines in corneal epithelial cells and in the rat desiccation model. Methods: A human corneal epithelial cell line (CEPI) was grown in keratinocyte growth medium 2 (KGM2) to approximately 80% confluence. The medium was aspirated and dishes were left for 0 to 30 min with the cover left open to dry the cells (short-term desiccation). After desiccation, KGM2 was added to the dishes and collected from the dishes 15 min later to measure the concentrations of cytokines in the medium by sandwich enzyme immunoassay (ELISA). Viability of the cells was estimated with alamer blue. To study the effect of long-term desiccation, cultivated cells on transwells were used. After dessiccation for up to 8 h, the viability of the cells and levels of cytokines in the culture medium were examined. The expression of cytokines in the cornea of the dry eye model rat was measured by real-time PCR. Results: Short-term dessication of CEPI cells significantly increased the interleukin (IL)-6 level and slightly increased the tumor necrosis factor (TNF)-α level. Anti-IL-6 antibody partially suppressed cell death caused by desiccation. Upon long-term desiccation, IL-6 and IL-8 levels were increased. In the dry eye model rats, the IL-6 mRNA level in the cornea significantly increased, whereas TNF-α mRNA level slightly increased. Conclusions: Desiccation induced IL-6 expression in corneal epithelial cells, suggesting that IL-6 participates in desiccation-induced cell death. © 2011 Molecular Vision.

Purpose: To evaluate the long-term outcome of cultivated oral mucosal epithelial transplantation (COMET) in treatment of eyes with total limbal stem cell deficiency. Design: Noncomparative, retrospective, interventional case series. Participants: Forty eyes in 36 patients with total limbal stem cell deficiency (Stevens-Johnson syndrome in 12 eyes, chemical or thermal burns in 11 eyes, ocular cicatricial pemphigoid [OCP] in 9 eyes, pseudo-OCP in 7 eyes, and gelatinous drop-like dystrophy in 1 eye) were treated at the Department of Ophthalmology, Tokyo Dental College, Chiba, Japan. Intervention: Cultivated autologous oral mucosal epithelial sheets were transplanted onto the ocular surface in eyes with total limbal stem cell deficiency. Main Outcome Measures: Reconstruction of a stable ocular surface with a clear appearance and no epithelial defects, reduction in fibrovascular tissue invasion of corneal surface, a functional fornix, change in visual acuity, and postoperative complications. Results: The mean follow-up period was 25.5 months (range, 654.9 months). Kaplan-Meier analysis of a corneal surface stability revealed an early decline in transplanted oral mucosal epithelial stability over the first 6 months, remaining comparatively stable thereafter (1 year, 64.8%; 2 years, 59.0%; and 3 years, 53.1%). Postoperative persistent epithelial failure developed within the first 3 months in 9 eyes. Early epithelial failure was associated closely with preoperative corneal defects. Gradual fibrovascular tissue invasion of the corneal surface was observed in 8 eyes and was marked in cases of OCP. Survival of a functional fornix decreased progressively until approximately 6 months. Postoperative visual acuity seemed to be related to the presence of corneal opacity. Complications included stromal melting or perforation in 8 eyes, infectious keratitis in 2 eyes, glaucoma in 8 eyes, and recurrence of herpetic keratitis in 1 eye. Corneal melting or perforation and infectious keratitis were associated closely with persistent epithelial defects after COMET. Conclusions: The transplantation of cultivated oral mucosal epithelial sheets offers a viable and safe alternative in the reconstruction of a stable ocular surface. Epithelialization of the corneal surface is very important not only in obtaining a satisfactory long-term outcome, but also in achieving a lower incidence of complications. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. © 2011 American Academy of Ophthalmology.

Purpose. To evaluate the extent of corneal inflammation and the response to treatment in patients with Mooren's ulcer, by in vivo confocal microscopy (IVCM). Methods. Twenty-two eyes of 15 patients with Mooren's ulcer were enrolled in this prospective study. All subjects underwent routine ophthalmic examinations, IVCM, and conjunctival histopathologic examination of specimens in patients undergoing conjunctival excision. Eyes with active ulcer were treated with topical corticosteroids and additional therapy, depending on the signs and symptoms. Eyes in remission continued to receive the previous treatment protocols. The relation between the severity of ulcer and inflammation status as assessed by IVCM was also studied. The endpoints were inflammatory cell density (ICD), counted by IVCM, and the extent of the limbal arc involved with ulcers. Results. Ten eyes had active corneal ulcers, and 12 eyes had been in remission for the past year. The mean ICD of eyes with active ulcers before treatment was 2092.7 ± 1538.6 cells/mm2 (range, 835.3-7832.7; 95% CI, 3232.5-952.9). Nine of the eyes improved at 8 weeks, with a decrease in ICD to 249.1 ± 109.0 cells/mm2 (range, 100.3-595.3; 95% CI, 329.8-168.3). One eye had corneal perforation, and ICD immediately before perforation was 1677.6 ± 247.6 cells/mm2. The mean ICD of 12 eyes in remission was 357.5 ± 266.8 cells/mm2 (range, 12.7-1127.0; 95% CI, 555.2-159.8). The correlation of the ICD and the extent of limbal involvement with ulcers was strong (R2 = 0.8119). Conclusions. ICD evaluated by IVCM is a useful and promising parameter for evaluation of the degree of inflammation in eyes with Mooren's ulcer and for assessment of response to treatment. © Association for Research in Vision and Ophthalmology.

Objective: We sought to examine the effect of resveratrol (3,4',5-trihydroxy-trans-stilbene), a plant-derived polyphenolic compound, on the development of abdominal aortic aneurysm (AAA). Methods: AAA was induced in mice by periaortic application of CaCl 2. NaCl (0.9%)-applied mice were used as a sham group. Mice were treated with intraperitoneal injection of PBS (Sham/CON, AAA/CON, n=30 for each) or resveratrol (100mg/kg/day) (AAA/RSVT, n=30). Six weeks after the operation, aortic tissue was excised for further examinations. Results: Aortic diameter was enlarged in AAA/CON compared with Sham/CON. Resveratrol treatment reduced the aneurysm size and inflammatory cell infiltration in the aortic wall compared with AAA/CON. Elastica Van Gieson staining showed destruction of the wavy morphology of the elastic lamellae in AAA/CON, while it was preserved in AAA/RSVT. The increased mRNA expression of monocyte chemotactic protein-1, tumor necrosis factor-α, intercellular adhesion molecule-1, CD68, vascular endothelial growth factor-A, p47, glutathione peroxidase (GPX)1 and GPX3 were attenuated by resveratrol treatment (all p<0.05). Administration of resveratrol decreased protein expression of phospho-p65 in AAA. The increased 8-hydroxy-2'-deoxyguanosine-positive cell count and 4-hydroxy-2-nonenal-positive cell count in AAA were also reduced by resveratrol treatment. Zymographic activity of matrix metalloproteinase (MMP)-9 and MMP-2 was lower in AAA/RSVT compared with AAA/CON (both p<0.05). Compared with AAA/CON, Mac-2 + macrophages and CD31 + vessels in the aortic wall were decreased in AAA/RSVT (both p<0.05). Conclusion: Treatment with resveratrol in mice prevented the development of CaCl 2-induced AAA, in association with reduced inflammation, oxidative stress, neoangiogenesis, and extracellular matrix disruption. These findings suggest therapeutic potential of resveratrol for AAA. © 2011 Elsevier Ireland Ltd.

We describe a T-shaped capsule stabilization hook (modified capsule expander [M-CE]) used for repositioning and scleral fixation of the lens capsule of subluxated lenses. The 5-0 polypropylene device is flexible and attached to a curved needle. The contact portion is bent at 1.25 mm, and the end bifurcates in a T configuration to form a 3.75 mm footpad from which the capsular bag can be suspended. Modified capsule expanders were implanted in 4 eyes of 4 patients with subluxated cataractous lenses and provided excellent support and centration of the intraocular lens (IOL)-capsular bag complex. The IOLs remained well centered and stable. The corrected distance visual acuity improved to at least 20/20 in all patients after surgery. Thus, M-CEs were effective in fixating the lens capsule to the sclera in patients with significant zonular weakness. Financial Disclosure: Saori Yaguchi, Y. Asano, T. Kozawa, T. Miyawaki, K. Negishi, and K. Tsubota have no financial or proprietary interest in any material or method mentioned. Additional disclosure is found in the footnotes. © 2011 ASCRS and ESCRS.

Purpose. To investigate the contribution of posterior corneal surfaces to higher-order aberrations (HOAs) of the cornea, optical quality, and visual acuity after keratoplasty. METHODS. Corneal topography of anterior and posterior surfaces and pachymetry were conducted using anterior segment optical coherence tomography (AS-OCT) in 40 eyes (10 eyes after penetrating keratoplasty [PK], 10 eyes after deep anterior lamellar keratoplasty [DALK], 10 eyes after Descemet's stripping automated endothelial keratoplasty [DSAEK], and 10 normal eyes). Anterior, posterior, and total corneal HOAs were calculated using ray-tracing and decomposition into Zernike polynomials and were evaluated as root mean square values. Modulation transfer functions (MTFs) were also evaluated. RESULTS. Topography maps of the anterior and posterior surfaces showed reverse patterns in the normal, PK, and DALK eyes, but not in DSAEK eyes. In the normal, PK, and DALK eyes, the total corneal HOAs were significantly smaller (~10%) than were the HOAs of the anterior surface (P<0.01), whereas there was no significant difference between total and anterior HOAs in the DSAEK eyes (P=0.483). In the normal, PK, and DALK eyes, the MTFs of the total cornea were slightly better than those of the anterior surface. In the DSAEK eyes, the MTFs of the total cornea were lower than those of the anterior surface. Visual acuity was significantly correlated with total and anterior surface HOAs (P<0.05). CONCLUSIONS. Posterior surfaces compensate for anterior aberrations in normal, PK, and DALK eyes. In DSAEK eyes, the posterior surface increased total corneal HOAs and had a negative influence on MTFs. © 2011 The Association for Research in Vision and Ophthalmology, Inc.

Purpose: Immunologic rejection remains a major cause of graft failure in high-risk corneal transplantation. This study was conducted to elucidate the efficacy and safety of systemic cyclosporine (CsA) in high-risk corneal transplantation. Design: Prospective, randomized, open-labeled clinical trial with a parallel-group study. Methods: Patients underwent high-risk corneal transplantation at the Department of Ophthalmology, Tokyo Dental College, Chiba, Japan. High-risk was defined as corneal neovascularization in more than 1 quadrant or a history of corneal grafting. Patients were assigned to either a systemic CsA group or a control group. Administration of CsA was continued for at least 6 months with blood CsA concentration 2 hours after administration of approximately 800 ng/mL, unless undesirable side effects developed. The main outcome measures were graft clarity, endothelial rejection, and local and systemic complications. Results: Forty patients were enrolled and 39 (18 men, 21 women; mean age, 67.4 ± 11.9 years) were analyzed. In the CsA group, CsA was discontinued within 6 months in 7 patients because of side effects. With a mean follow-up of 42.7 months, endothelial rejection developed in 6 and 2 eyes in the CsA and control groups, respectively. No differences were observed in the rates of graft clarity loss between the 2 groups (P = .16, Kaplan-Meier analysis). Conclusions: No positive effect of systemic CsA administration for suppressing rejection in high-risk corneal transplantation was observed. With a relatively high incidence of systemic side effects, the results suggest that this protocol should not be recommended for corneal transplant recipients, especially those of advanced age. © 2011 Elsevier Inc.