Norihiko Honda

Identification of Schlemm's Canal and Its Surrounding Tissues by Anterior Segment Fourier Domain Optical Coherence Tomography

PURPOSE To identify Schlemms canal (SC) and trabecular meshwork (TM) by anterior segment Fourier-domain optical coherence tomography (AS-FD-OCT) with histologic confirmation in enucleated human eyes and to quantitatively evaluate SC and TM in living human eyes. METHODS In enucleated human eyes, the imaging of the anterior chamber angle by AS-FD-OCT was performed before and after surgical expansion of SC with an injection of a viscoelastic material, followed by histologic examination. In 60 living human eyes, the agreement of identification of SC between examiners was evaluated with the Cohens κ values, and the lengths of SC and TM and the area of TM were measured on temporal and nasal sections of the AS-FD-OCT images. RESULTS In enucleated human eyes, SC was observed to be a thin, linear, lucent space in the AS-FD-OCT image obtained with the high-definition raster scan protocol, but not in those obtained with the bi-angle radial scan protocol. This space was enlarged after the SC expansion. In the histologic study, the SC was confirmed to be in the same position as in the AS-FD-OCT images. The κ values of observable SC in living human subjects were 0.92 or higher. The axial length of the SC averaged 347.2 ± 42.3 μm, TM length 466.9 ± 60.7 μm, and TM area 0.0671 ± 0.0058 mm². These measurements showed sufficient repeatability and reproducibility. CONCLUSIONS Using the high-definition images of the AS-FD-OCT, SC and its surrounding tissues were successfully observed in most of the living eyes and were quantitatively evaluated in a noninvasive manner.

Changes of Conjunctivochalasis with Age in a Hospital-based Study

PURPOSE To assess the relationship between age and the incidence and severity of conjunctivochalasis by using the grading system for conjunctivochalasis proposed by Meller and Tseng. DESIGN Prospective, nonrandomized, consecutive case study. METHODS A total of 1,416 patients aged one to 94 years were enrolled. The age, gender, medical history, ocular history, and grade and parameters of conjunctivochalasis at three locations (nasal, middle, and temporal) were determined in all subject. RESULTS The prevalence of conjunctivochalasis increased dramatically with age (one to 10 years, 6.8%; 11 to 20 years, 36.2%; 21 to 30 years, 61.5%; 31 to 40 years, 71.4%; 41 to 50 years, 90.2%; 51 to 60 years, 94.2%; 61 to 70 years, 98.0%; 71 to 80 years, 99.0%; 81 to 90 years, 98.5%; and 91 to 100 years, 100.0%). The mean grade of conjunctivochalasis was higher in female patients than in male patients (nasal area, P = .0229; temporal area, P = .0078) and was higher for the temporal conjunctiva than the nasal conjunctiva (P < .0000001). Parameters such as the downward gaze- or digital pressure-dependent changes of conjunctivochalasis and the presence of superficial punctate keratitis all increased with age. These conjunctivochalasis-related parameters were correlated with the severity of conjunctivochalasis (P < .00001), especially of the middle bulbar conjunctiva. CONCLUSIONS We report the grade of conjunctivochalasis in a large series of consecutive patients. Our results strongly suggest that conjunctivochalasis is an age-dependent eye disease that occurs in young adulthood and thereafter. The present grading system should be useful for future clinical studies of conjunctivochalasis.

Longitudinal Changes in Corneal Irregular Astigmatism and Visual Acuity in Eyes with Keratoconus

PurposeTo quantitatively investigate the time course of changes in corneal irregular astigmatism and their relation to best spectacle-corrected visual acuity (BSCVA) in eyes with keratoconus.MethodsSubjects were 47 patients (57 eyes) with keratoconus who had undergone videokeratography examinations at least twice, with an interval of 1 year or longer between each examination. By means of Fourier series harmonic analysis, topography data were separated into spherical component, regular astigmatism, asymmetry, and higher order irregularity.ResultsIn eyes that showed apparent progression on color-coded maps, the yearly rate of change was significantly positive for spherical component (P = 0.03) and higher order irregularity (P = 0.006). In eyes with apparent progression, the yearly change rate of BSCVA was significantly positive (P = 0.001), but not in the eyes without apparent progression (P = 0.1655). In eyes with progression on maps, the yearly change rate of BSCVA was significantly correlated with the change rate of higher order irregularity per year (r = 0.770, P = 0.0004).ConclusionsThe results indicated that progression of keratoconus is associated with deterioration of BSCVA, which is in turn significantly correlated with increases in corneal higher order irregularity. Jpn J Ophthalmol 2007;51:265–269 @ Japanese Ophthalmological Society 2007

Longitudinal analysis of corneal topography in suspected keratoconus

Aims: To examine the incidence of progression of suspected keratoconus to true keratoconus and compare quantitative descriptors of corneal topography between eyes with and without progression. Methods: 34 eyes with suspected keratoconus were retrospectively reviewed in 34 patients. Their age at the initial examination was 13 to 40 years (24.1 (7.5), mean (SD)), and the follow-up periods ranged from 3 to 10 years (6.0 (2.2) years). Suspected keratoconus was defined as the fellow eye of a clinically apparent keratoconus but that had no slit-lamp signs of keratoconus (Fleischer ring, Vogt striae and Munson sign) with a best spectacle-corrected visual acuity of 20/20 or better. Eyes were monitored for the progression of apparent slit-lamp findings of keratoconus during the follow-up period. Using a Fourier analysis of the corneal topography data, regular astigmatism, asymmetry component and higher-order irregularity component were calculated in the central 3 mm zone. Quantitative descriptors of corneal topography were compared between eyes which progressed to true keratoconus and those which did not. Results: Five eyes (14.7%) progressed to apparent keratoconus from suspected keratoconus (progression group), and 29 eyes did not (non-progression group). On average, it took 5.2 years for the eyes to develop apparent slit-lamp findings of keratoconus. The cumulative incidence of progression by Kaplan–Meier analysis was 21.5% in 6 years. The asymmetry component and regular astigmatism by Fourier analysis at the initial examination were significantly larger in the progression group than in the non-progression group. Conclusion: In our retrospective study, approximately 20% of eyes with suspected keratoconus progressed to true keratoconus in 6 years, and these eyes had presented greater asymmetry and regular astigmatism at the initial examination.

Extended long-term results of penetrating keratoplasty for keratoconus.

Purpose: To investigate the extended long-term results of penetrating keratoplasty (PK) for keratoconus. Methods: The subjects were all patients with clinical keratoconus who underwent initial PK at University of Tokyo from 1971 to 1990 and whose medical records were available. Data were retrieved from the medical records. Kaplan-Meier survival analysis was performed to estimate the cumulative probability of immune reaction-free grafts and graft survival. Results: One hundred twenty-five eyes in 125 patients met the entry criteria. The average age at the time of PK was 25.0 ± 8.9 years. With an average follow-up period of 15.3 ± 9.7 years, 12 eyes (9.6%) experienced rejection and 5 eyes (4.0%) experienced graft failure. Average best-corrected visual acuity in logarithm of the minimum angle of resolution at preoperation, 10, 20, and 25 years after surgery was 1.54 ± 0.68, 0.06 ± 0.22, 0.03 ± 0.17, and 0.14 ± 0.42, respectively. The cumulative probability of graft survival at 10, 20, and 25 years after PK was 98.8%, 97.0%, and 93.2%, respectively. Conclusions: Recovery of visual acuity was good after PK for keratoconus in an extended follow-up. The graft survival rate, however, gradually decreased 20 years after PK.

Recent Causes of Subconjunctival Hemorrhage

Purpose: To assess the relationship between the incidence of subconjunctival hemorrhage (SCH) and age during each season of the year, and to examine recent risk factors for SCH. Methods: A total of 161 patients with SCH aged 1–94 years were involved in the study. The age, gender, medical history and ocular history were determined for all subjects. Results: The peak age of onset of SCH was between 61 and 70 years. Fourteen patients (77.7%) had trauma or contact-lens-induced injury, and 4 patients (22.3%) among the younger patients aged 0–40 years had an unknown etiology. Among the older patients aged 61–94 years, the chief risk factor for SCH was hypertension (47.5%), followed by unknown etiology (39.4%) and then diabetes (13.1%). Conclusion: These results suggest that the major current risk factors for SCH are trauma and contact-lens-induced injury in younger patients, while hypertension is the main factor in older patients. The incidence of acute hemorrhagic conjunctivitis was decreased.

Effect of Latanoprost on the Expression of Matrix Metalloproteinases and Tissue Inhibitor of Metalloproteinase 1 on the Ocular Surface

OBJECTIVE To investigate the effect of topical latanoprost on the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase 1 (TIMP-1) on the ocular surface. METHODS Tears were collected from 39 patients with glaucoma who used latanoprost, 0.005%, eyedrops (Xalatan) and 28 healthy volunteers. The MMP-9 concentration was measured. Conjunctival epithelial cells were collected from 10 eyes of 10 patients before and 1 to 3 months after starting to take topical latanoprost, 0.005%, and MMP-1, MMP-9, and TIMP-1 messenger RNA (mRNA) expression was analyzed. Both eyes of 48 mice were treated once a day with latanoprost, 0.005%, timolol gel, 0.5%, eyedrops, vehicle of Xalatan, or phosphate-buffered saline, and MMP-9 and TIMP-1 mRNA expression was analyzed. RESULTS The median MMP-9 concentration in latanoprost-treated cases was 91.2 ng/mL (in controls, 19.7 ng/mL; P < .001). In latanoprost-treated cases, the relative ratio of MMP-9 to glyceraldehyde 3-phosphate dehydrogenase mRNA was significantly increased from 6.42 to 21.3 (P = .04, paired t test) and the relative amount of TIMP-1 was significantly decreased from 154 to 105 (P = .009). The relative amount of MMP-1 to GAPDH mRNA before and after latanoprost use was not significantly different (P = .16). In mice, MMP-9 expression was increased and TIMP-1 expression was decreased on the ocular surface at 8 weeks after latanoprost use. CONCLUSION The topical use of latanoprost increases MMP-1 and MMP-9 and decreases TIMP-1 on the ocular surface. CLINICAL RELEVANCE The use of topical latanoprost might not be recommended in patients with keratoconus or after laser-assisted in situ keratomileusis.

Descemet stripping automated endothelial keratoplasty using cultured corneal endothelial cells in a rabbit model.

OBJECTIVE To investigate the feasibility of Descemet stripping automated endothelial keratoplasty (DSAEK) using cultured human corneal endothelial cells (HCECs) in an animal model. METHODS Descemet stripping automated endothelial keratoplasty grafts were produced by seeding cultured HCEC suspensions onto human corneal stromal discs. Three insertion techniques were assessed in an ex vivo model. The feasibility of DSAEK grafts with cultured HCECs was examined in a rabbit model. Rabbits received stromal disc transplants with cultured HCECs (c-DSAEK) or without HCECs (controls). RESULTS The HCECs on the DSAEK grafts had a consistent size and polygonal shape. Mean (SD) percentage of cell loss in the taco-folding group (38.7% [5.2%]) was significantly greater than that in the Busin glide (11.6% [1.5%]; P = .001) and lens glide (18.0% [5.4%]; P = .007) groups. Corneal transparency gradually recovered in the c-DSAEK group, whereas edema persisted for up to 28 days in controls. Histologic examination after surgery revealed donor HCECs covering the posterior surface of the graft in the c-DSAEK group. CONCLUSIONS Further enhancements of the efficacy and safety of DSAEK using cultured HCECs will make this a clinically feasible alternative therapy for corneal endothelial dysfunction. CLINICAL RELEVANCE Descemet stripping automated endothelial keratoplasty using cultured HCECs may be a novel therapeutic approach to treat corneal endothelial dysfunction.

In Vivo Confocal Microscopy of Hereditary Sensory and Autonomic Neuropathy

Purpose: To observe the morphology of the corneal cells and corneal nerve fibers in patients with type IV or V hereditary sensory and autonomic neuropathy (HSAN) by in vivo confocal microscopy and elucidate the mechanism leading to the loss of corneal sensation in this disease. Methods: In vivo confocal microscopy was performed on the central cornea of the right eye in 3 patients with HSAN (ages 17, 20, and 32 years), and their corneal morphology was compared with that of 3 healthy subjects (ages 28, 30, and 36 years). Corneal sensation was tested with a Cochet-Bonnet esthesiometer. Results: The superficial epithelial cell density was lower in the HSAN patients compared with the healthy subjects (1525, 1225, and 1250/mm2 vs. 2225, 1750, and 2500/mm2), but the basal epithelial cell density of the patients was similar to that of the healthy subjects. Nerve bundles were clearly observed in the sub-basal nerve plexus layer of the cornea in the healthy subjects, but were undetectable at the central cornea in the patients with HSAN. The corneal sensation of the patients with HSAN was much weaker than that of the healthy subjects (2.79, 40.30, and 132.50 g/mm2 vs. 1.47, 1.47, and 1.47 g/mm2). Conclusions: Superficial keratopathy accompanied with neurotrophic keratopathy and tear film instability observed clinically agrees with the large keratinized cells in the superficial corneal epithelium by in vivo confocal microscopy in these patients. Our findings suggest that the loss of corneal nerves contributes to impairment of corneal sensation in patients with type IV or V HSAN.

Conjunctivochalasis and Contact Lenses

PURPOSE To assess the relationship between age and the incidence and severity of conjunctivochalasis in contact lens (CL) wearers by grading of conjunctivochalasis, and to compare the severity of conjunctivochalasis between CL wearers and nonwearers. DESIGN Prospective, nonrandomized consecutive case study. METHODS A total of 600 CL wearers (94 hard CLs [HCL] and 506 soft CLs [SCL]) aged 11 to 60 years and 579 nonwearers aged 10 to 60 years were enrolled. The age, gender, medical history, ocular history, and the grade and other parameters of conjunctivochalasis at 3 locations (nasal, middle, and temporal areas) were determined in all subjects. RESULTS The prevalence of conjunctivochalasis increased dramatically with age in all groups. The mean grade of conjunctivochalasis was higher in CL wearers than in nonwearers (nasal area, P < .00001; temporal area, P < .00001) and was higher in HCL wearers than in SCL wearers (nasal area, P < .00001; temporal area, P = .00003). Parameters such as the downward gaze-dependent or digital pressure-dependent changes of conjunctivochalasis and the presence of superficial punctate keratitis all increased with age in both CL wearers and nonwearers. The gaze-dependent and pressure-dependent changes of conjunctivochalasis showed an increase with age and the duration of CL wear in both SCL and HCL wearers. CONCLUSIONS This was the first assessment of the severity of conjunctivochalasis in a large series of consecutive CL wearers. Our results strongly suggest that wearing CLs is an important risk factor for conjunctivochalasis.