Potential roles of MNREAD acuity charts and contrast/glare sensitivity in Ranibizumab treatment of branch retinal vein occlusion.

BACKGROUND/OBJECTIVES: To investigate the potential utility of MNREAD acuity charts and contrast/glare sensitivity (CGS) assessment for evaluating the efficacy of an initial treatment with ranibizumab (Lucentis®) for branch retinal vein occlusion (BRVO). METHODS: Intravitreal injections of ranibizumab were administered in 43 eyes of 43 treatment-naïve patients with BRVO. Efficacy was assessed 1 month later. Best-corrected far/near visual acuity (BCFVA/BCNVA), MNREAD parameters (reading acuity [RA], maximum reading speed [MRS], critical print size [CPS]), CGS (CS/GS), and central macular thickness (CMT) in optical coherence tomography (OCT) before and after treatment were evaluated. The area (superior/inferior) affected by BRVO was determined by fluorescein angiography. RESULTS: All parameters improved significantly following treatment (p < 0.05), and all MNREAD and CGS parameters were significantly correlated with BCVA in the treated eye before and after treatment (p < 0.01). The changes in BCFVA, BCNVA, MRS, and CS were significantly correlated with the amount of change in CMT (p < 0.007; r = 0.415, 0.528, -0.465, and -0.508, respectively). MRS exhibited a percentage change that was significantly correlated with that in CMT (p < 0.007; r = -0.511). Additionally, MRS exhibited the lowest threshold CMT (397 µm) at which the most significant change in improvement was observed. CMT was less likely to improve if BRVO occurred at a superior site than if it occurred at an inferior site (0.05 < p = 0.07 < 0.1). CONCLUSIONS: MNREAD and CGS testing were useful for evaluating BRVO treatment efficacy. MRS might be a valuable index for evaluating treatment success and making treatment decisions.

Spatial distribution of macular pigment estimated by autofluorescence imaging in elderly Japanese individuals.

PURPOSE: To determine the spatial distribution types of macular pigment (MP) in elderly Japanese individuals and to consider their origin. STUDY DESIGN: Observational case series. METHODS: Local MP optical density (MPOD) at some eccentricities and MP volume were measured using the MPOD module of a MultiColor Spectralis in 96 pseudophakic eyes of 96 participants (age range, 52-86 years; mean age, 72.8 ± 8.3 years). The MP distribution types were determined from the MP spatial profiles. The retinal thickness (RT) at the foveal center, at both 0.5° and 0.9° eccentricities, and the foveal width were measured using optical coherence tomography. RESULTS: The mean local MPOD at the foveal center was 0.79. Spatial distribution was classified into four types: central peak (24.0%), ring-like (40.6%), intermediate (22.9%), and central dip (12.5%). The ring-like type was the most frequent in these Japanese participants. The central-peak type showed lower MPOD than did the other types in the area outside 0.9°. The ring-like type occurred frequently in eyes with small RT at 0.5° and wider foveal width. A rough contour of the Müller cell cone was found more frequently in the central-dip type than in the other types. CONCLUSIONS: The present characteristics of the different distribution patterns could be explained by the hypothesis that MP presents mainly in the Müller cell cone within 0.5° and in Müller cells in the outer and inner plexiform layers in the area outside 0.5°. The anatomic characteristics of Müller cells at the fovea and parafovea likely affect the MP distribution.

Skin Carotenoid Index in a large Japanese population sample.

Carotenoids are anti-oxidative agents. Human skin and eyes contain specific carotenoid species known to prevent various pathologies caused by oxidative stress. We quantified skin and eye carotenoid levels and investigated their potential correlation in a population including 985 Japanese patients and staff members of an ophthalmology clinic (577 men, 408 women, mean age of 69.7 ± 13.6 [SD]). Skin carotenoid (SC) and macular pigment (MP) levels were measured with reflection spectroscopy and autofluorescence imaging methods, respectively. The mean SC index was 343.1 ± 142.1 (SD). SC indices for women were higher than for men (382 vs 315, p < 0.001). Smokers and overweight subjects (BMI ≥ 25) had lower SC indices. Subjects taking lutein supplements had higher SC indices than non-supplementing subjects (415 vs 325, p < 0.001). SC and MP indices were significantly correlated. The obtained data set can be used for reference purposes by Japanese subjects and researchers interested in tissue responses to diets high in carotenoids and lutein supplementation.

Optic coherence tomography appearances of retinal astrocytic hamartoma and systemic features in tuberous sclerosis of Japanese patients.

PURPOSE: To describe the optical coherence tomography findings of retinal astrocytic hamartoma of tuberous sclerosis and to confirm the association between the type of retinal astrocytic hamartoma and systemic manifestations in Japanese patients. STUDY DESIGN: A retrospective observational case series. METHODS: The medical records of 35 patients with tuberous sclerosis who underwent ophthalmological examination were reviewed. The retinal astrocytic hamartomas were classified into four types based on the optical coherence tomography findings, and their association with systemic disease was evaluated. RESULTS: A total of 40 retinal astrocytic hamartomas in 13 eyes of eight patients aged 4-28 years were identified. Optical coherence tomography images were obtained for 23 lesions in 10 eyes of seven patients. Retinal astrocytic hamartomas were seen as protruding lesions of varying heights (maximum thickness, range between 221 to 1043 µm). Of the 23, 15 lesions showed homogeneous reflectivity; in six lesions, hyper-reflective spots that presumably represented intratumoral calcification were noted. Vitreous changes were noted in 13 lesions; vitreous seeding by retinal astrocytic hamartoma was observed in seven eyes. There were no significant differences in the rates of each systemic feature among the optical coherence tomography types. CONCLUSION: Retinal astrocytic hamartomas were classified into four types according to the previous reports; however, this classification may be worthless because the extent of protrusion did not correspond to the intratumoral characteristics, and the involved depth of the retina was not same even in the same type. An association between the type of retinal astrocytic hamartoma and systemic manifestations was not confirmed in this small case series. We considered that the classification of retinal astrocytic hamartoma and its association with systemic manifestations need further study.

Grade of Cataract and Its Influence on Measurement of Macular Pigment Optical Density Using Autofluorescence Imaging.

Purpose: To evaluate the influence of cataracts on measuring macular pigment optical density (MPOD) using a dual-wavelength confocal scanning autofluorescence imaging technique and to establish methods to compensate for the influence of cataracts. Methods: This prospective case series comprised 100 eyes that underwent cataract surgery. Cataracts were graded based on the World Health Organization classification. MPOD levels were measured with the MPOD module of the Spectralis MultiColor instrument (Spectralis-MP), pre- and postoperatively. We investigated the relationship between change in MPOD values and age, cataract grade, and quality of autofluorescence images. Local MPOD levels were evaluated for four strategically chosen eccentricities within the macular region, and the total MPOD volume was evaluated within 8.98° eccentricity from the center. Results: MPOD levels could be obtained in 67 eyes before surgery. Local and volume MPOD levels were higher postoperatively relative to preoperatively in all eyes. The mean ratio of local MPOD levels after and before surgery (correction factor, CF) ranged from 1.42 to 1.77, with larger CFs required for eccentricities closer to the foveal center. The CF for the MPOD volume was 1.31. Age, grade of nuclear cataract (NUC), posterior subcapsular opacity, and image quality index (IQI) significantly contributed to CFs. For example, regression equation for CF at 0.23° = 0.17 + 0.16 × IQI + 0.29 × NUC grade + 0.01 × age (P < 0.001). Conclusions: Cataracts affected MPOD measurements with the Spectralis-MP, but corrected MPOD results could be obtained via regression equations.

Optical Detection of Macular Pigment Formation in Premature Infants.

PURPOSE: To demonstrate the presence of macular pigment in the retina of premature infants, and to examine its changes with age. METHODS: The participants included 40 premature infants. Infants who had received laser photocoagulation for retinopathy of prematurity were excluded. Macular pigment optical density (MPOD) was measured by fundus reflectometry using RetCam3, a digital fundus camera. The reflection imaging was performed for ROP screening. The imaging time points were from a post menstrual age (PMA) of 29 weeks 0 days to 46 weeks 5 days. RESULTS: The MPOD levels could be obtained from 39 premature infants. The levels at the first measurement ranged from 0 to 0.18 (mean 0.076, SD 0.044). The earliest time, when a nonvanishing MPOD level was obtained, was at a PMA of 33 weeks and 2 days, and that level was 0.05. The initial examination MPOD levels showed a moderate correlation with age (R2 = 0.32, P < 0.00017). The mean MPOD levels measured each week during the follow-up period showed a very strong correlation with age (R2 = 0.91, P < 0.0001). A regression line of MPOD = 0.0069 × age - 0.1783 was derived, where age is counted in PMA days. CONCLUSIONS: The MPOD levels of premature infants were for the first time measured in living eyes. Macular pigment increased linearly with age. TRANSLATIONAL RELEVANCE: Macular pigment increased with the development of macular morphology. This result suggested the importance of nutritional management of infants and mothers during perinatal period.

Reliability of a commercially available heterochromatic flicker photometer, the MPS2, for measuring the macular pigment optical density of a Japanese population.

PURPOSE: The macular pigment optical density (MPOD) of a Japanese population was measured using a commercially based heterochromatic flicker photometer, the Macular Pigment Screener (MPS2). The objective of the study was to evaluate the accuracy and test-retest reliability of the MPS2 in Asian pigmented eyes. STUDY DESIGN: Experimental study to validate the medical instrument in humans. METHODS: Twenty-four healthy Japanese participants with no systemic or eye diseases (men: 13, women: 11; mean [SD] age 38.6 [10.9 years]) were included. The concordance of the MPOD, obtained using the MPS2 and Macular Metrics II (MM2), and the test-retest reliability were examined. RESULTS: Determination of the MPOD was unsuccessful in 1 participant; thus, the MPOD of 23 participants was analyzed. The mean (SD) MPOD measured with the detail-mode of the MPS2 was 0.63 (0.18) and with that of the MM2, it was 0.72 (0.23). The former was significantly lower than the latter (P = .003, paired t test). The MPOD measured with the MPS2 and the MM2 showed good concordance (r = 0.79, P < .001, Pearson product moment correlation). Bland-Altman analyses showed no systematic errors between the MPS2 and the MM2. The intraclass correlation coefficient over 5 measurement times with the detail-mode of the MPS2 was 0.80, and the mean coefficient of variation was 9.4%. CONCLUSION: The high concordance with the MM2 and good test-retest reliability found by this study suggest that the MPS2 is acceptable for use in a Japanese population. However, the mean MPOD yielded by the MPS2 was significantly lower than that yielded by the MM2. Therefore, the MPS2 and MM2 are not interchangeable in a single study.

Reliability of a two-wavelength autofluorescence technique by Heidelberg Spectralis to measure macular pigment optical density in Asian subjects.

This study evaluates the accuracy of an objective two-wavelength fundus autofluorescence technique for the purpose of measuring the macular pigment optical density (MPOD) in Asian pigmented eyes. Potential differences between MPOD values obtained via autofluorescence technique and subjective heterochromatic photometry (HFP) were examined. Inter-examiner reproducibility between three examiners and test-retest reliability over five time points were also explored. Subjects were 27 healthy Japanese volunteers aged 24 to 58 (mean ±â€¯standard deviation, 40.2 ±â€¯9.0) years. An MPOD module of the Spectralis MultiColor instrument configuration (Spectralis-MP) was used for the autofluorescence technique, and a Macular Metrics Densitometer (MM) was used for HFP. The mean MPOD values at 0.25° and 0.5° eccentricities using the Spectralis-MP were 0.51 ±â€¯0.12 and 0.48 ±â€¯0.13, respectively. In comparison, the MM based values were 0.72 ±â€¯0.23 and 0.61 ±â€¯0.25, respectively. High correlations between the Spectralis-MP and MM instrument were found (Pearson's correlation coefficients of 0.73 and 0.87 at 0.25° and 0.5° eccentricities, respectively), but there was a systematic bias: the MPOD values by MM method were significantly higher than those by Spectralis-MP at 0.25° eccentricity. High inter-examiner reproducibility and test-retest reliability were found for MM measurements at 0.5° eccentricity, but not at 0.25°. The Spectralis-MP showed less inter-examiner and test-retest variability than the MM instrument at 0.25° and 0.5° eccentricities. We conclude that the Spectralis-MP, given its high agreement with the HFP method and due to its higher reproducibility and reliability, is well suited for clinical measurements of MPOD levels in Asian pigmented eyes.

Evidence of Carotenoid in Surgically Removed Lamellar Hole-Associated Epiretinal Proliferation.

Purpose: To determine the constituents and origin of the yellow pigment in surgically removed lamellar hole-associated epiretinal proliferation (LHEP) in patients with lamellar macular hole (LMH). Methods: This prospective case series comprised nine eyes with LMH in patients aged 41 to 83 years. The presence of LHEP was confirmed by preoperative optical coherence tomography; the distribution of macular pigment was observed by two-wavelength fundus autofluorescence technique before and after surgery. The subjects underwent a 25-gauge vitrectomy, and the surgically removed epiretinal membranous tissue was fixed with formalin. The specimens were examined using resonance Raman microscopy, and paraffin sections were stained with antiglial fibrillary acidic protein. Results: Seven cases presented with LHEP, and the presence of yellow pigment was confirmed using an operating microscope. Carotenoid-specific Raman signals with three major Raman peaks could be identified in the specimens with LHEP. These specimens were positive for glial fibrillary acidic protein staining. Using the fundus autofluorescence technique, a central defect in the distribution of the macular pigment was noted in the exact area of the lamellar hole. This type of defect was no longer visible after surgical repair of the lamellar hole. Conclusions: The constituents of the yellow pigment in the removed LHEP were carotenoids that typically originate from the macular xanthophyll pigments at the fovea. Since LHEP is reported to be composed of Müller cells, we hypothesize that xanthophyll carotenoids at the fovea are contained in the Müller cells.

[Anti-vascular Endothelial Growth Factor Therapy on Exudative Age-related Macular Degeneration in Routine Clinical Practice of a Single Site: the Effectiveness of Cases Followed for More than Two Years].

PURPOSE: To investigate the long-term effectiveness of as-needed anti-vascular endothelial growth factor therapy on age-related macular degeneration (AMD). SUBJECTS AND METHODS: The number of treatments, treatment period, visual acuity and morphological changes were investigated retrospectively in 257 eyes of 248 patients (189 men and 59 women, mean age ± SD; 71.1 ± 9.2 years old) who were followed up for two years and more. Re-treatment was mainly decided based on patient's will. RESULTS: The mean number of treatments was 6.4 3.8 in the observational period of 3.7 years. Exudative changes were resolved at least once in the observational period in 240 eyes, and 160 eyes had no exudative changes at the final visit. Type 2 neovascularization by Gass resulted in fibrotic scar more frequently than type 1. The mean decimal visual acuity was 0.36 before the initiation of treatment and 0.26 at the final visit. The treatment period was less than 100 days in 54 eyes, and multivariate analysis revealed that polypoidal choroidal vasculopathy (PCV) was a factor of prolonged treatment period. No severe adverse effects were admitted locally and systemically. CONCLUSIONS: The deterioration of mean visual acuity was assumed to be due to the relatively small number of treatments. Twenty-one percent of all eyes preserved well without any recurrence of treatments for short periods, and PCV needed treatments for longer periods than typical AMD.

Autofluorescence imaging of macular pigment: influence and correction of ocular media opacities.

The healthy adult human retina contains in its macular region a high concentration of blue-light absorbing carotenoid compounds, known as macular pigment (MP). Consisting of the carotenoids lutein, zeaxanthin, and meso-zeaxanthin, the MP is thought to shield the vulnerable tissue layers in the retina from lightinduced damage through its function as an optical attenuator and to protect the tissue cells within its immediate vicinity through its function as a potent antioxidant. Autofluorescence imaging (AFI) is emerging as a viable optical method for MP screening of large subject populations, for tracking of MP changes over time, and for monitoring MP uptake in response to dietary supplementation. To investigate the influence of ocular media opacities on AFI-based MP measurements, in particular, the influence of lens cataracts, we conducted a clinical trial with a large subject population (93 subjects) measured before and after cataract surgery. General AFI image contrast, retinal blood vessel contrast, and presurgery lens opacity scores [Lens Opacities Classification System III (LOCS III)] were investigated as potential predictors for image degradation. These clinical results show that lens cataracts can severely degrade the achievable pixel contrasts in the AFI images, which results in nominal MP optical density levels that are artifactually reduced. While LOCS III scores and blood vessel contrast are found to be only a weak predictor for this effect, a strong correlation exists between the reduction factor and the image contrast, which can be quantified via pixel intensity histogram parameters. Choosing the base width of the histogram, the presence or absence of ocular media opacities can be determined and, if needed, the nominal MP levels can be corrected with factors depending on the strength of the opacity.

Long-term outcomes and prognostic factors for trabeculectomy with mitomycin C in eyes with uveitic glaucoma: a retrospective cohort study.

PURPOSE: To elucidate the long-term outcomes and prognostic factors for trabeculectomy with mitomycin C (MMC) in eyes with uveitic glaucoma (UG). METHODS: A retrospective, consecutive, comparative cohort study was conducted with 204 patients who underwent trabeculectomy with MMC between 1999 and 2008 at 2 Japanese clinical centers. The study group included 101 eyes with UG and 103 eyes with primary open-angle glaucoma (POAG). Surgical failure was defined as intraocular pressure levels of ≥21 mm Hg or an additional glaucoma surgery. Kaplan-Meier survival curves for surgical failure were compared between UG and POAG eyes, and prognostic factors for surgical failure of trabeculectomy in UG eyes were analyzed by the Cox proportional hazards model. Secondary outcome measures included comparisons of the frequency of additional cataract surgery and other surgical complications after trabeculectomy between UG and POAG eyes. RESULTS: The mean follow-up periods (±SD) were 34.7±37.9 and 37.7±34.7 months (median, 24.0 and 27.4 mo) for UG and POAG, respectively. The subtypes of uveitis were granulomatous uveitis (n=20) including sarcoidosis (n=12), Vogt-Koyanagi-Harada disease (n=5) and varicella zoster virus uveitis (n=3), Behçet disease (n=10), Posner-Schlossman syndrome (n=5), and other types of UG (n=12). Fifty-four eyes were diagnosed with idiopathic UG. The 3-year probabilities of success after trabeculectomy were 71.3% and 89.7% for UG and POAG, respectively (P=0.0171). A multivariable model showed that UG eyes with previous cataract surgery [relative risk (RR)=2.957, P=0.0344)] and granulomatous uveitis (RR=3.805, P=0.0106) were associated with surgical failure. UG eyes experienced more frequent cataract surgeries after trabeculectomy than POAG eyes: the 3-year probabilities of additional cataract surgery of 62.6% and 10.7% for UG and POAG, respectively (P<0.0001). There was no significant difference in the frequency of surgical complications such as bleb leakage, hypotensive maculopathy, severe anterior-chamber hemorrhage, and infectious endophthalmitis. CONCLUSIONS: Trabeculectomy with MMC was less effective in maintaining intraocular pressure reduction in UG eyes than in POAG eyes. The prognostic factors for surgical failure of trabeculectomy in UG eyes were previous cataract surgery and granulomatous uveitis. In addition, UG eyes after trabeculectomy more frequently required additional cataract surgery.

Preoperative and postoperative optical coherence tomography findings in patients with rhegmatogenous retinal detachment involving the macular region.

Purpose. To evaluate morphologic changes of the macula, we observed eyes with rhegmatogenous retinal detachment (RRD) involving the macular region by optical coherence tomography (OCT). Subjects and Methods. We studied 26 eyes with RRD before and after surgery, assessing visual acuity, the height of retinal detachment at the fovea (HRD), and morphologic changes of the macular region. The interval between the onset and surgery was also determined. We examined the external limiting membrane (ELM) after surgery and the continuity of the inner segment-outer segment junction (IS/OS junction) of the photoreceptor layer. Results. Impairment of visual acuity was observed when HRD was over 1,000 µ m, when there was outer nuclear layer edema before surgery, and when there was IS/OS junction disruption 3 months after surgery. However, 67% of eyes with a continuous ELM and IS/OS junction disruption 3 months after surgery eventually showed restoration of the continuity of IS/OS junction at 6 months. Conclusions. Impairment of visual acuity was observed in eyes with HRD >1,000 µ m, preoperative outer nuclear layer edema, and IS/OS junction disruption 3 months postoperatively. It is suggested that continuity of ELM might affect restoration of IS/OS junction after surgery for retinal detachment.

Trabeculectomy with mitomycin for open-angle glaucoma in phakic vs pseudophakic eyes after phacoemulsification.

OBJECTIVE: To determine whether previous phacoemulsification adversely affects surgical prognosis of trabeculectomy with mitomycin for open-angle glaucoma. METHODS: The study is a retrospective, consecutive, comparative case series. At 2 clinical centers, we reviewed 226 medical records of eyes with open-angle glaucoma undergoing initial trabeculectomy, including 175 phakic eyes (phakic group) and 51 pseudophakic eyes that had previously undergone phacoemulsification with superior conjunctival incision (pseudophakic group). Primary outcome was the probability of success after trabeculectomy. Surgical failure was defined as an additional glaucoma surgery or 1 of the following 3 criteria: intraocular pressure (IOP) of 21 mm Hg or greater (A); IOP of 18 mm Hg or greater (B); and IOP of 15 mm Hg or greater (C). Multivariable analysis was performed using the Cox proportional hazards model. RESULTS: The mean follow-up period was 37.5 months. The probability of success for criteria A, B, and C at 1 and 3 years in the phakic vs the pseudophakic group was 97.8% and 92.6%, respectively, vs 78.6% and 65.1%, respectively, for criterion A (P < .001); 92.9% and 81.3%, respectively, vs 72.8% and 63.7%, respectively, for criterion B (P = .004); and 73.1% and 54.2%, respectively, vs 53.1% and 38.4%, respectively, for criterion C (P = .009). The multivariable model confirmed that pseudophakia independently contributes to surgical failure (criterion A relative risk, 4.59 [P < .001]; criterion B, 2.88 [P = .004]; and criterion C, 2.02 [P = .009]). The pseudophakic group required more postoperative laser suture lysis (P = .01). CONCLUSION: Previous phacoemulsification is a prognostic factor for surgical failure of trabeculectomy with mitomycin for open-angle glaucoma.

The epithelium takes center stage in allergic keratoconjunctivitis.

PURPOSE: To investigate the role of the epithelium in severe allergic conjunctivitis. METHODS: We first investigated the expression of protease-activated receptors (PARs) in cultured human conjunctival epithelial cells and fibroblasts by reverse transcription-polymerase chain reaction. Next, we examined whether mite allergen-stimulated cells release chemokines and whether physiological protease inhibitors such as secretory leukocyte protease inhibitor (SLPI) and α1-antitrypsin can inhibit their production. We also looked at the expression of thymic stromal lymphopoietin (TSLP) in giant papillae of patients with vernal keratoconjunctivitis and examined whether the as Toll-like receptor 3 ligand polyinosinic:polycytidylic acid (poly I:C) can induce expression of TSLP in cultured human conjunctival epithelial cells. RESULTS: PAR 1, PAR2, and PAR3 were expressed in cultured human conjunctival epithelial cells and fibroblasts at mRNA level. These epithelial cells released interleukin (IL) 6 and IL-8, with an upregulation in their gene expression, in response to the serine protease activity of mite allergens. This response was inhibited by SLPI and α1-antitrypsin. Transforming growth factor ß1 decreased the production of SLPI in corneal and conjunctival epithelial cells. TSLP was expressed in giant papillae epithelium in patients with vernal keratoconjunctivitis at mRNA and protein levels. Poly I:C induced expression of TSLP in cultured conjunctival epithelial cells at mRNA level. Costimulation with TSLP and IL-33 had a synergistic effect for IL-13 mRNA expression in cultured human mast cells. CONCLUSIONS: Imbalance between protease of mite allergens and innate protease inhibitors of the epithelium may induce inflammation and disrupt barrier function. Viral infection may induce expression of TSLP via Toll-like receptors and release IL-33 by necrosis. These phenomena promote excessive allergic reactions; hence, the epithelium takes "center stage" in allergic conjunctivitis.

SLPI prevents cytokine release in mite protease-exposed conjunctival epithelial cells.

House dust mites are a major source of allergens associated with allergic diseases including allergic conjunctivitis. Here, we demonstrate that mite-derived serine protease activity induces the release of cytokines from human ocular conjunctival epithelial cells in vitro and innate antiproteases, secretory leukocyte protease inhibitor (SLPI) and alpha1-antitrypsin, can inhibit the response. An extract prepared from a whole-mite culture induced the release of IL-6 and IL-8 and upregulated their gene expression in the human conjunctival epithelial cell line Chang, responses which were inhibited not only by a synthetic serine protease-specific inhibitor, AEBSF, but also by SLPI and alpha1-antitrypsin at a physiologically relevant concentration. The findings suggest a homeostatic role for SLPI and alpha1-antitrypsin against the proteases contained in allergen sources in the ocular conjunctiva and that exposure to house dust particles containing mite-derived serine protease activity could be involved in the initiation of sensitization through the ocular conjunctival epithelium and/or exacerbation of allergic conjunctivitis.

A novel mutation in the cornea-specific keratin 12 gene in Meesmann corneal dystrophy.

PURPOSE: To report a novel mutation in the keratin 12 gene (KRT12) found in a Japanese family in association with Meesmann corneal dystrophy (MECD). METHODS: After informed consent was obtained, genomic DNA was extracted from the leukocytes of the peripheral blood of the proband, her affected father, normal mother, and 50 normal unrelated volunteers. Exons 1-8 of the KRT12 gene were amplified by polymerase chain reaction and directly sequenced. RESULTS: A novel heterozygous T to G transversion at the second nucleotide position of codon 433 (CTG>CGG), resulting in the replacement of leucine by arginine at codon 433 of the KRT12 gene (L433R), was detected in the proband and her affected father but not in her normal mother or the 50 controls. CONCLUSIONS: The novel L433R mutation of the KRT12 gene found in two members of this Japanese family caused MECD.