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Purpose: Various immune mediators have crucial roles in the pathogenesis of intraocular diseases. Machine learning can be used to automatically select and weigh various predictors to develop models maximizing predictive power. However, these techniques have not yet been applied extensively in studies focused on intraocular diseases. We evaluated whether 5 machine learning algorithms applied to the data of immune-mediator levels in aqueous humor can predict the actual diagnoses of 17 selected intraocular diseases and identified which immune mediators drive the predictive power of a machine learning model., Design: Cross-sectional study., Participants: Five hundred twelve eyes with diagnoses from among 17 intraocular diseases., Methods: Aqueous humor samples were collected, and the concentrations of 28 immune mediators were determined using a cytometric bead array. Each immune mediator was ranked according to its importance using 5 machine learning algorithms. Stratified k-fold cross-validation was used in evaluation of algorithms with the dataset divided into training and test datasets., Main Outcome Measures: The algorithms were evaluated in terms of precision, recall, accuracy, F-score, area under the receiver operating characteristic curve, area under the precision-recall curve, and mean decrease in Gini index., Results: Among the 5 machine learning models, random forest (RF) yielded the highest classification accuracy in multiclass differentiation of 17 intraocular diseases. The RF prediction models for vitreoretinal lymphoma, acute retinal necrosis, endophthalmitis, rhegmatogenous retinal detachment, and primary open-angle glaucoma achieved the highest classification accuracy, precision, and recall. Random forest recognized vitreoretinal lymphoma, acute retinal necrosis, endophthalmitis, rhegmatogenous retinal detachment, and primary open-angle glaucoma with the top 5 F-scores. The 3 highest-ranking relevant immune mediators were interleukin (IL)-10, interferon-γ-inducible protein (IP)-10, and angiogenin for prediction of vitreoretinal lymphoma; monokine induced by interferon γ, interferon γ, and IP-10 for acute retinal necrosis; and IL-6, granulocyte colony-stimulating factor, and IL-8 for endophthalmitis., Conclusions: Random forest algorithms based on 28 immune mediators in aqueous humor successfully predicted the diagnosis of vitreoretinal lymphoma, acute retinal necrosis, and endophthalmitis. Overall, the findings of the present study contribute to increased knowledge on new biomarkers that potentially can facilitate diagnosis of intraocular diseases in the future., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine the association of retinal thickness with cognitive function in Japanese persons., Design: Cross-sectional, population-based survey., Participants: A total of 1293 Japanese persons aged 65 to 86 years who resided in the Saku area in the Japan Public Health Center-Based Prospective Study participated in the eye and mental health screening., Methods: Participants underwent comprehensive ophthalmic assessment, including fundus photography, measurement of intraocular pressure, and determination of refraction status. We assessed the thickness of the macular retinal nerve fiber layer (mRNFL), ganglion cell-inner plexiform layer (GC-IPL), and ganglion cell complex (GCC, which includes the retinal nerve fiber layer and GC-IPL), and the full thickness in the macula and peripapillary retinal nerve fiber layer (ppRNFL) using spectral-domain (SD) OCT. Cognitive tests consisted of the Mini-Mental State Examination, Wechsler Memory Scale Revised logical memory I/II subtest, clock drawing test, and Clinical Dementia Rating Scale. These were used to designate the participants in the following 3 groups: Normal, those with mild cognitive impairment (MCI), and those with dementia. Multivariable logistic regression models were used to analyze associations between retinal thickness and cognitive function after adjusting potential confounding factors., Main Outcome Measures: Association of retinal thickness with cognitive function., Results: Among the 1293 potential subjects, 114 were excluded for a diagnosis of depression, 64 were excluded for retinal disease, and 140 were excluded for scanning errors or suboptimal OCT images. The remaining 975 participants (mean age, 73.2 years) were included in this analysis. Significant differences were found in the 3 groups in all layers and GCC thickness, but not in ppRNFL thickness. After adjusting for age, sex, educational status, and refraction, full macular thickness and GCC thickness were inversely associated with the presence of dementia, but ppRNFL thickness was not. Furthermore, GC-IPL, GCC, and full macular thicknesses were all associated with the presence of dementia in the inferior sectors., Conclusions: Macular thickness was associated with the presence of dementia, but ppRNFL was not. Our results suggest that OCT measurements of the macula could be superior to those of the ppRNFL in assessing neurodegenerative changes and a potentially useful diagnostic biomarker of cognitive function., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To describe the clinical and genetic characteristics of the cohort enrolled in the East Asian studies of occult macular dystrophy (OMD)., Design: International, multicenter, retrospective cohort studies., Participants: A total of 36 participants from 21 families with a clinical diagnosis of OMD and harboring pathogenic RP1L1 variants (i.e., Miyake disease) were enrolled from 3 centers in Japan, China, and South Korea., Methods: A detailed history was obtained, and comprehensive ophthalmological examinations including spectral-domain OCT were performed. All detected sequence variants in the RP1L1 gene were reviewed, and in silico analysis was performed, including allele frequency analyses and pathogenicity predictions., Main Outcome Measures: Onset of disease, visual acuity (VA) converted to the logarithm of the minimum angle of resolution (logMAR), OCT findings, and effect of detected variants., Results: Eleven families from Japan, 6 from South Korea, and 4 from China were recruited. There were 12 female and 24 male participants. The median age of onset was 25.5 years (range, 2-73), and the median age at the latest examination was 46.0 years (range, 11-86). The median VA (logMAR) was 0.65 (range, -0.08-1.22) in the right eye and 0.65 (-0.08-1.10) in the left eye. A significant correlation between onset of disease and VA was revealed. The Classical morphologic phenotype showing both blurred ellipsoid zone and absence of interdigitation zone of the photoreceptors was demonstrated in 30 patients (83.3%), and subtle photoreceptor architectural changes were demonstrated in 6 patients (16.6%). Eight pathogenic RP1L1 variants were identified, including 6 reported variants and 1 novel variant: p.R45W, p.T1194M/p.T1196I (complex), p.S1199C, p.G1200A, p.G1200D, p.V1201G, and p.S1198F, respectively. Two variants were recurrent: p.R45W (11 families, 52.4%) and p.S1199C (5 families, 23.8%). The pathogenic missense variants in 10 families (47.6%) were located within the previously reported unique motif, including 6 amino acids (1196-1201)., Conclusions: There is a large spectrum of clinical findings in Miyake disease, including various onset of disease and VA, whereas the characteristic photoreceptor microstructures were shared in most cases. Two hot spots including amino acid numbers 45 and 1196-1201 in the RP1L1 gene were confirmed in the East Asian population., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the effect of meibomian gland dysfunction (MGD) and friction-related disease (FRD) on the severity of dry eye disease (DED)., Design: Cross-sectional observational study., Participants: This study enrolled 449 patients with DED (63 men and 386 women; mean age, 62.6±15.7 years [range, 21-90 years]) for analysis., Methods: Subjective symptoms, the ocular surface, tear function, and the presence of MGD and FRD (superior limbic keratoconjunctivitis, conjunctivochalasis, and lid wiper epitheliopathy) were investigated., Main Outcome Measures: Schirmer value, tear film breakup time (TBUT), and keratoconjunctival score., Results: We classified the participants into aqueous-deficient dry eye (ADDE; n = 231 [51.4%]) and short TBUT dry eye subtype (TBUT-DE; n = 109 [24.3%]) subgroups. The TBUT was shorter in patients with MGD than in those without MGD, whereas other ocular signs showed no difference (TBUT: MGD present, 1.97±1.02 seconds; MGD absent, 2.94±1.63 seconds [P < 0.001]; ADDE/MGD present, 1.94±1.08 seconds; ADDE/MGD absent, 2.77±1.61 seconds [P < 0.001]; short TBUT-DE/MGD present, 2.07±0.97 seconds; short TBUT-DE/MGD absent, 2.94±1.23 seconds [P = 0.01]). The ADDE patients with FRD showed a worse TBUT than ADDE patients without FRD (TBUT: ADDE/FRD present, 2.08±1.39 seconds; ADDE/FRD absent, 2.92±1.54 seconds; P < 0.001)., Conclusions: This study showed associations between MGD, FRD, or both and ocular signs in DED. In the presence of MGD, FRD, or both, TBUT was significantly shortened regardless of the dry eye status or subtype., (Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To compare tear film parameters as well as meibomian gland morphologic features and function among patients with meibomian gland dysfunction (MGD), those with non-Sjögren syndrome aqueous-deficient dry eye (non-SS ADDE), those with non-SS ADDE and MGD, and normal subjects., Design: Multicenter, cross-sectional, observational case series., Participants: Forty-one eyes of 41 patients (all women; mean age ± standard deviation, 62.1±9.9 years) with non-SS ADDE, 70 eyes of 70 patients (all women; 66.0±8.7 years) with MGD, 17 eyes of 17 patients (all women; 72.4±7.8 years) with non-SS ADDE and MGD, and 70 eyes of 70 normal control subjects (all women; 65.0±7.1 years)., Methods: Ocular symptoms were scored from 0 to 14 and lid margin abnormalities from 0 to 4 according to their respective number. Meibomian gland changes were scored from 0 to 6 (meiboscore) on the basis of noncontact meibography findings, and meibum was graded from 0 to 3 depending on its volume and quality. Conjunctival and corneal epithelial damage were scored from 0 to 9 (fluorescein score). Tear film break-up time (TBUT) was measured as an index of tear film stability, and tear fluid production was evaluated with Schirmer's test., Main Outcome Measures: Ocular symptom score, lid margin abnormality score, meiboscore, meibum grade, fluorescein score, TBUT, and Schirmer's test value., Results: The ocular symptom score did not differ significantly between the MGD and non-SS ADDE groups (P = 0.762). The lid margin abnormality score, meiboscore, and meibum grade were significantly higher in the MGD group than in the non-SS ADDE group (P = 0.0012, P < 0.0001, and P < 0.0001, respectively). The fluorescein score, TBUT, and Schirmer's test value were significantly worse in the non-SS ADDE group than in the MGD group (P < 0.0001, P = 0.0061, and P < 0.0001, respectively). The meiboscore correlated significantly with Schirmer's test value only in the MGD group (ρ = 0.508, P = 8.3×10(-6))., Conclusions: An increase in tear fluid production likely compensates for loss of meibomian glands in individuals with MGD., (Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To describe the clinical and molecular characteristics of patients with childhood-onset Stargardt disease (STGD)., Design: Retrospective case series., Participants: Forty-two patients who were diagnosed with STGD in childhood at a single institution between January 2001 and January 2012., Methods: A detailed history and a comprehensive ophthalmic examination were undertaken, including color fundus photography, autofluorescence imaging, spectral-domain optical coherence tomography (SD-OCT), and pattern and full-field electroretinograms. The entire coding region and splice sites of ABCA4 were screened using a next-generation, sequencing-based strategy. The molecular genetic findings of childhood-onset STGD patients were compared with those of adult-onset patients., Main Outcome Measures: Clinical, imaging, electrophysiologic, and molecular genetic findings., Results: The median ages of onset and the median age at baseline examination were 8.5 (range, 3-16) and 12.0 years (range, 7-16), respectively. The median baseline logarithm of the minimum angle of resolution visual acuity was 0.74. At baseline, 26 of 39 patients (67%) with available photographs had macular atrophy with macular/peripheral flecks; 11 (28%) had macular atrophy without flecks; 1 (2.5%) had numerous flecks without macular atrophy; and 1 (2.5%) had a normal fundus appearance. Flecks were not identified at baseline in 12 patients (31%). SD-OCT detected foveal outer retinal disruption in all 21 patients with available images. Electrophysiologic assessment demonstrated retinal dysfunction confined to the macula in 9 patients (36%), macular and generalized cone dysfunction in 1 subject (4%), and macular and generalized cone and rod dysfunction in 15 individuals (60%). At least 1 disease-causing ABCA4 variant was identified in 38 patients (90%), including 13 novel variants; ≥2 variants were identified in 34 patients (81%). Patients with childhood-onset STGD more frequently harbored 2 deleterious variants (18% vs 5%) compared with patients with adult-onset STGD., Conclusions: Childhood-onset STGD is associated with severe visual loss, early morphologic changes, and often generalized retinal dysfunction, despite often having less severe fundus abnormalities on examination. One third of children do not have flecks at presentation. The relatively high proportion of deleterious ABCA4 variants supports the hypothesis that earlier onset disease is often owing to more severe variants in ABCA4 than those found in adult-onset disease., (Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To describe the phenotypic presentation of a cohort of individuals with homozygous disease-associated ABCA4 variants., Design: Retrospective case series., Participants: Eighteen affected individuals from 13 families ascertained from a total cohort of 214 families with ABCA4-related retinal disease presenting to a single center., Methods: A detailed history was obtained, and color fundus photography, autofluorescence (AF) imaging, optical coherence tomography (OCT), and electrophysiologic assessment were performed. Phenotypes based on ophthalmoscopy, AF, and electrophysiology were assigned using previously reported characteristics. ABCA4 mutation detection was performed using the ABCR400 microarray (Asper Biotech, Tartu, Estonia) and high-throughput DNA sequencing, with direct sequencing used to assess segregation., Main Outcome Measures: Detailed clinical, electrophysiologic, and molecular genetic findings., Results: Eleven disease-associated homozygous ABCA4 alleles were identified, including 1 frame shift, 2 stops, 1 intronic variant causing splice-site alteration, 2 complex missense variants, and 5 missense variants: p.Glu905fsX916, p.Arg1300X, p.Gln2220X, c.4253+4 C>T, p.Leu541Pro and p.Ala1038Val (homozygosity for complex allele), p.Val931Met and p.Arg1705Gln (complex allele), p.Arg212Cys, p.Cys1488Arg, p.Arg1640Trp, p.Gly1961Glu, and p.Leu2027Phe. Eight of these 11 homozygous alleles have not been reported previously. Six of 7 patients with homozygous null alleles had early-onset (<10 years) disease, with all 7 having a severe phenotype. Two patients with homozygous missense variants (p.Leu541Pro and p.Ala1038Val [complex], and p.Arg1640Trp) presented with a severe phenotype. Three patients with homozygous p.Gly1961Glu had adult-onset disease and a mild phenotype. One patient with homozygous p.Leu2027Phe showed a spared fovea and preserved visual acuity., Conclusions: The phenotypes represented in patients identified as homozygous for presumed disease-associated ABCA4 variants gives insight into the effect of individual alleles. Null alleles have severe functional effects, and certain missense variants are similar to nulls, suggesting complete abrogation of protein function. The common alleles identified, p.Gly1961Glu and p. Leu2027Phe, both have a mild structural and functional effect on the adult retina; the latter is associated with relatively retained photoreceptor architecture and function at the fovea., (Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To clarify meibomian gland (MG) alterations in atopic keratoconjunctivitis (AKC) patients and compare the findings with obstructive MG dysfunction (MGD) patients and control subjects using in vivo confocal microscopy (CM)., Design: Prospective, controlled, single-center study., Participants: Twelve AKC patients (10 males, 2 females; mean age, 31.0±16.5 years), 12 obstructive MGD patients (7 males, 5 females; mean age, 37.6±5.6 years), and 26 control subjects (13 males, 13 females; mean age, 32.9±5.7 years) were recruited. No significant age or gender differences were observed between the 3 groups., Methods: All subjects underwent assessment of tear evaporation rate from the ocular surface (TEROS), slit-lamp examinations, tear break-up time (BUT) measurements, vital staining, Schirmer test I, meibography, MG expressibility, and CM examination of the MG (HRTII-RCM). Statistical analysis was performed using the Mann-Whitney test., Main Outcome Measures: The MG acinar unit density, inflammatory cell density, MG acinar unit longest diameter, MG acinar unit shortest diameter, and MG acinar unit area as observed by in vivo CM, MG drop-out, MG expressibility grading, tear stability, tear evaporation, and vital staining scores., Results: The TEROS values, mean BUT, vital staining scores, MG expressibility, and MG dropout grades were significantly worse in AKC patients compared with those in obstructive MGD patients and controls (P<0.05). The mean values of the CM parameters in AKC patients were significantly worse than those observed in the obstructive MGD patients and controls (P<0.001)., Conclusions: Changes in MG in AKC patients seem to be more severe than in patients with obstructive MGD and controls. In vivo CM is a noninvasive, efficient tool in the assessment of MG status and ocular surface disease in AKC., (Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the dose-dependent efficacy and safety of diquafosol ophthalmic solution for the treatment of dry eye syndrome., Design: Randomized, double-masked, multicenter, parallel-group, placebo-controlled trial., Participants: A total of 286 Japanese patients with dry eye who were prescribed topical diquafosol (1%, n = 96; 3%, n = 96) or placebo ophthalmic solution (n = 94)., Methods: After a washout period of 2 weeks, qualified subjects were randomized to receive a single drop of 1% or 3% diquafosol or placebo ophthalmic solutions 6 times per day for 6 weeks., Main Outcome Measures: The primary outcome measure was fluorescein corneal staining score assessment. The secondary outcome measures were Rose Bengal corneal and conjunctival staining scores, tear break-up time (BUT), and subjective symptom assessment. Safety measures were clinical blood and urine examination and recording of adverse events., Results: Fluorescein corneal staining scores significantly improved with both 1% and 3% topical diquafosol compared with placebo at 4 weeks, respectively (P = 0.037, P = 0.002). There was a dose-dependent effect among the groups. Rose Bengal corneal and conjunctival staining scores also improved significantly with both 1% and 3% diquafosol compared with placebo (P = 0.007 and P = 0.004, respectively). Subjective dry eye symptom scores significantly improved with both diquafosol ophthalmic solutions (P ≤ 0.033), although there were no significant differences in BUT compared with placebo. No significant differences between the treatment groups were observed in relation to the occurrence of adverse events., Conclusions: Both 1% and 3% diquafosol ophthalmic solutions are considered effective and safe for the treatment of dry eye syndrome., (Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To estimate the prevalence and risk factors of dry eye disease (DED) in a rural setting in Japan., Design: Cross-sectional study., Participants: We included 3294 subjects, aged ≥ 40 years who were in the residential registry for Koumi town., Intervention: Subjects in a rural mountain area, Koumi town, completed questionnaires designed to detect dry eye diagnosis and risk factors., Main Outcome Measures: Clinically diagnosed DED was defined as the presence of a previous clinical diagnosis of DED by ophthalmologists or severe symptoms of DED (both dryness and irritation constantly or often). Current symptoms of DED and possible risk factors such as age, gender, educational history, smoking history, alcohol drinking history, height and weight, visual display terminal (VDT) use, and contact lens (CL) wear, and past/current history of certain common systemic diseases were the main outcome measures. We used logistic regression analysis to examine associations between DED and other demographic factors., Results: Of the 3294 eligible residents, 2791 residents (85%) completed the questionnaire. The percentage of women with a composite outcome of clinically diagnosed DED or severe symptoms (21.6%; 95% confidence interval [CI], 19.5-23.9) was higher than that of men (12.5%; 95% CI, 10.7-14.5; P<0.001). A low body mass index (BMI; odds ratio [OR], 2.07; 95% CI, 0.98-4.39), CL use (OR, 3.84; 95% CI, 1.46-10.10), and hypertension (HT) (OR, 1.39; 95% CI, 0.94-2.06) were risk factors for DED in men. Use of a VDT (OR, 2.33; 95% CI, 1.12-4.85), CL use (OR, 3.61; 95% CI, 2.13-6.10), and myocardial infarction or angina were the risk factors (OR, 2.64; 95% CI, 1.51-4.62), whereas high BMI was a preventive factor (OR, 0.69; 95% CI, 0.48-1.01) for DED in women., Conclusions: Among a Japanese cohort, DED leading to a clinical diagnosis or severe symptoms is prevalent. Use of CLs was a common dry eye risk factor in both genders. The condition is more prevalent in men with low BMI, HT, and in women with myocardial infarction or angina and VDT use. Relevant measures directed against the modifiable risks may provide a positive impact on public health and quality of life of Japanese., Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

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, 6-54.9 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., (Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the efficacy, sensitivity and specificity of confocal microscopy (CM) parameters: meibomian gland (MG) acinar longest diameter (MGALD), MG acinar shortest diameter (MGASD), inflammatory cell density (ICD), and MG acinar unit density (MGAUD) in the diagnosis of MG dysfunction (MGD)., Design: Prospective, controlled, single-center study., Participants: Twenty MGD patients (9 males, 11 females; mean age, 63.5+/-16.5 years) and 26 age- and gender-matched control subjects (13 males, 13 females; mean age, 53.2+/-15.7 years) were recruited., Methods: All subjects underwent slit-lamp examinations, tear film break-up time (BUT) measurements, assessment of tear evaporation rate from the ocular surface (TEROS), vital stainings, Schirmer test, meibography, MG expressibility, and CM of the MG. Data were compared between the 2 groups using the Mann-Whitney and chi-square tests., Main Outcome Measures: The correlation between the clinical findings of tear functions, vital staining scores, and the 4 CM parameters were tested by Spearman's correlation coefficient by rank test. Receiver operating characteristic curve technique was used to evaluate the sensitivity, specificity, and cutoff values of CM parameters., Results: The mean tear film BUT, vital staining scores, TEROS values, MG expressibility, and MG dropout grades by meibography were significantly worse in MGD patients compared with controls (P<0.001). The mean values of the MGALD, MGASD, ICD, and MGAUD in MGD patients were significantly worse than those observed in the controls with CM. All CM parameters showed a strong, significant correlation with tear functions, ocular surface vital stainings, MG expressibility, and MG dropout grades. The cutoff values for MGALD, MGASD, ICD, and MGAUD in the diagnosis of MGD were 65 microm, 25 microm, 300 cells/mm2, and 70 glands/mm2, respectively. The sensitivity and specificity values of these parameters under these cutoff values were 90% and 81% for MGALD, 86% and 96% for MGASD, 100% and 100% for ICD, 81% and 81% for MGAUD., Conclusions: Confocal microscopy has the potential to diagnose the simple MGD with high sensitivity and specificity. The CM-based diagnostic parameters correlated significantly and strongly with the status of the ocular surface disease., Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article., (Copyright 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To analyze risk factors of traumatic wound rupture after penetrating keratoplasty (PKP) or deep anterior lamellar keratoplasty (DALK)., Design: Retrospective case series., Participants: A total of 1962 consecutive cases were included., Methods: A review of consecutive patients undergoing either PKP (1776 eyes) or DALK (186 eyes) at 1 regional center between 1998 and 2006 was carried out to determine the incidence of traumatic globe rupture after keratoplasty. Ophthalmic and demographic factors were analyzed. A comparison with previous literature was performed., Main Outcome and Measures: Incidence, causes, and final visual acuity., Results: Of 43 eyes with globe rupture during this period, 36 received keratoplasty during this study period. The incidence of globe rupture after keratoplasty was 1.8% (36/1962). These 36 cases consisted of 35 of the 1776 eyes receiving PKP (2.0%) and 1 of the 186 eyes receiving DALK (0.5%). Globe rupture occurred 61.6+/-50.0 months (mean +/- standard deviation) after keratoplasty in 43 cases. The major cause of trauma was a fall in elderly patients (73.2+/-8.4 years, 17 eyes), with lens damage occurring in all such cases. Although 15 eyes (34.9%) had a visual acuity of 20/200 or better at final follow-up, eyes showing lens damage were associated with poorer visual acuity than eyes with no lens damage (P<0.01)., Conclusions: Wound weakness persisted for a long period after keratoplasty. A fall was observed frequently in elderly patients and resulted in poor visual outcome. Globe rupture associated with lens injury could be the predictor for future visual outcome.

Objective: To determine the prevalence of dry eye disease (DED) and risk factors among young and middle-aged Japanese office workers using visual display terminals (VDTs)., Design: Cross-sectional prevalence survey., Participants: Four thousand three hundred ninety-three Japanese young and middle-aged office workers using VDTs., Intervention: Office workers completed questionnaires sent by e-mail designed to detect dry eye diagnosis and risk factors., Main Outcome Measures: Clinically diagnosed DED was defined as the presence of a previous clinical diagnosis of DED by dry eye specialists or severe symptoms of DED (both dryness and irritation constantly or often). Current symptoms of DED and possible risk factors such as age, duration of VDT use, type of VDT work, environmental factors, presence of systemic diseases, systemic medicine use, smoking history, and contact lens (CL) use were the main outcome measures. We used logistic regression to examine associations between DED and other demographic factors., Results: Of the 4393 office workers, 3549 (80.1%) completed the questionnaire. Clinically diagnosed DED was present in 266 (10.1%) of 2640 male subjects and in 195 (21.5%) of 909 female subjects. Severe symptoms of DED were observed in 711 male and in 436 female participants. More than 4 hours of VDT use was associated with an increased risk of DED (odds ratio [OR], 1.68; 95% confidence interval [CI], 1.40-2.02). In addition, CL use (OR, 3.91; 95% CI, 3.37-4.53) increased the risk of severe dry eye symptoms., Conclusions: Dry eye disease leading to a clinical diagnosis or severe symptoms is prevalent among young and middle-aged Japanese office workers. The condition is more prevalent among females, CL wearers, and prolonged VDT users. Relevant measures directed against the modifiable risks could provide a positive impact on public health and quality of life of office workers., Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article.

Objective: To elucidate the morphologic alterations of the cornea in atopic keratoconjunctivitis (AKC) using confocal microscopy (Heidelberg Retina Tomograph II-Rostock Cornea Module: HRT-II RCM)., Design: Prospective comparative study., Participants: We studied 21 right eyes of 21 AKC patients (11 males, 10 females; mean age, 26.3 years) as well as 19 right eyes of 19 normal subjects (12 males, 7 females; mean age, 28.4 years)., Methods: All subjects underwent corneal sensitivity measurements, Schirmer test, tear film break-up time, fluorescein and Rose Bengal stainings, and HRT-II confocal laser scanning microscopy of the central cornea., Main Outcome Measures: The epithelial and endothelial cell densities of the central cornea, the density of subbasal long nerve fibers (LNFs) and total nerve branches (NBs) of the subbasal nerve plexus were calculated. The morphologic characteristics of the corneal nerves were studied. Correlation between nerve density, tear functions, and ocular surface examination parameters were investigated., Results: The corneal sensitivity, tear stability and vital staining scores were significantly worse in eyes with AKC (P<0.01). Eyes with AKC showed a significantly lower density of basal epithelial cells, LNFs, and NBs compared with normal eyes. Nerve fiber abnormalities such as increased tortuosity, bifurcation abnormality, sharp deflections, and thickening of stromal nerves, as well as several inflammatory cells in close proximity of the subbasal and stromal nerve fibers were observed., Conclusions: The corneal disease in AKC was associated with significant alterations of the basal epithelium, and subbasal and stromal corneal nerves, which related to the changes in tear functions and corneal sensitivity. Confocal scanning laser microscopy was useful to study the pathological in vivo corneal changes in AKC.

Purpose: To estimate the incidence of and investigate possible risk factors for postkeratoplasty atopic sclerokeratitis in keratoconus patients undergoing keratoplasty., Design: Retrospective, noncomparative, interventional case series., Participants: Two hundred forty-seven eyes with keratoconus., Methods: We reviewed the medical records of all keratoplasty cases of keratoconus between May 2000 and December 2005 at Tokyo Dental College Ichikawa General Hospital. The incidence and clinical details of cases consistent with postkeratoplasty atopic sclerokeratitis were recorded., Main Outcome Measures: Cases with acute sclerokeratitis during the early postoperative period were retrospectively evaluated., Results: A total of 247 keratoconus eyes were followed at our clinic after keratoplasty (mean follow-up, 18.5+/-13.0 months). Thirty-five eyes of 29 patients (14.2%) had a history of atopic dermatitis, of which 6 eyes of 5 patients (2.4%) developed postkeratoplasty atopic sclerokeratitis. Mean age of postkeratoplasty atopic sclerokeratitis patients was 29 years (range, 23-39). The mean period between keratoplasty and onset of postkeratoplasty atopic sclerokeratitis was 26 days (range, 11-41). Loosening of running sutures and wound leakage were observed in 3 eyes; persistent epithelial defects in 3 eyes; and graft melting in 2 eyes, 1 of which was perforated. Preoperative atopic blepharitis and corneal neovascularization were identified as risk factors for postkeratoplasty atopic sclerokeratitis., Conclusions: Postkeratoplasty atopic sclerokeratitis is a potentially severe complication in atopic patients undergoing keratoplasty. Systemic immunosuppression may be considered in patients with active blepharitis and corneal neovascularization.

Purpose: To investigate the efficacy and safety of LASIK over a 5-year postoperative period., Design: Observational case series., Participants: We examined 779 eyes in 402 patients with myopia or myopic astigmatism who underwent LASIK to correct their refractive errors and received regular postoperative assessments for 5 years., Methods: Postoperative examinations were performed 1 day; 1 week; 1, 3, and 6 months; and 1, 2, 3, 4, and 5 years after LASIK surgery., Main Outcome Measures: We evaluated changes in uncorrected visual acuity (UCVA) (logarithm of the minimum angle of resolution [logMAR]), manifest refraction, best-corrected visual acuity (BCVA) (logMAR), intraocular pressure, corneal thickness, corneal endothelial cell counts, and complications., Results: Preoperative UCVA of 1.27 improved to -0.03 at 1 day after surgery and -0.08 at 1 month and revealed minimal but significant decreases thereafter. Postoperative manifest refraction was also improved by surgery, showing minimal but significant regression after 1 year. Final BCVA loss was seen in 10 eyes of 7 patients; in 7 cases, there were obvious reasons such as the progression of cataracts in 3 eyes, epithelial disintegrity due to dry eye in 2 eyes, irregular astigmatism due to flap striae in 1 eye, and age-related macular dystrophy in 1 eye. Intraocular pressure and corneal thickness decreased by 4.0 mmHg and 76.9 microm, respectively, due to surgery, but remained stable throughout the follow-up period. Corneal endothelial cell counts (2689.0+/-232.9 cells/mm(2) before surgery) showed a statistically significant decrease at 5 years after surgery (2658.0+/-183.1 cells/mm(2); 1.2% loss for 5 years), likely within the range due to physiological age-related loss. No serious, vision-threatening, irreversible complication such as keratectasia or progressive endothelial cell loss was observed., Conclusion: LASIK surgery is an effective and safe procedure for correcting myopia/myopic astigmatism as long as inclusion and exclusion criteria are strictly respected. However, minimal regression occurred during the 5-year investigative period.

Purpose: To evaluate and grade the extent and severity of chronic ocular manifestations in Stevens-Johnson syndrome (SJS)., Design: Prospective multicenter case series., Participants: We enrolled 73 patients (138 eyes) with SJS seen between April 2003 and March 2005 at 3 tertiary referral centers., Methods: Patients with a confirmed history of SJS and chronic ocular complications that persisted for at least 1 year from the onset of SJS were included. Their detailed medical history and ophthalmic examination results were recorded on an itemized data collection form. Complications were categorized as corneal, conjunctival, and eyelid complications, and 13 components were evaluated and graded on a scale from 0 to 3 according to their severity., Main Outcome Measures: These were broadly classified as corneal (superficial punctate keratopathy, epithelial defect, loss of the palisades of Vogt, conjunctivalization, neovascularization, opacification, keratinization), conjunctival (hyperemia, symblepharon formation), and eyelid (trichiasis, mucocutaneous junction involvement, meibomian gland involvement, punctal damage) complications., Results: The most severely affected complication components were loss of the palisades of Vogt (114 eyes; 82.6%) and meibomian gland involvement (102 eyes; 73.9%). Visual acuity in 74 of the 138 eyes (53.6%) was worse than 20/200. The severity of corneal, conjunctival, and eyelid complications was significantly correlated with visual loss. All 13 complications were correlated significantly with logarithm of the minimum angle of resolution (logMAR) visual acuity; the correlation coefficient (R) ranged from 0.359 to 0.810 (P<0.0001); for corneal epithelial defects, R was 0.169 (P = 0.0473). Eyes with a higher total score for the 3 complication categories had poorer vision (R = 0.806; P<0.0001). Multivariate regression analysis showed that corneal neovascularization, opacification, keratinization, and cataracts significantly affected logMAR visual acuity (P<0.0001, P<0.0001, P = 0.0142, P = 0.0375, respectively)., Conclusions: The authors describe a new method for grading the extent and severity of ocular involvement in patients with SJS and demonstrate that the severity of ocular involvement is correlated significantly with the final visual outcome. This new grading system provides a more objective method for evaluating SJS patients and may be adapted for use in other cicatricial ocular surface diseases.

Purpose: To evaluate structural changes in the cornea and anterior chamber (AC) after LASIK for myopia., Design: Retrospective nonrandomized study., Participants: One hundred sixty-one eyes of 83 patients (mean age, 34.5+/-8.3 years) who underwent uneventful LASIK for myopia and myopic astigmatism. The preoperative refractive error (spherical equivalent) and corneal thickness were -6.02+/-2.10 diopters (D) and 549.9+/-29.3 mum, respectively., Methods: The AC volume (ACV), AC depth (ACD), corneal thickness, central corneal true net power, and posterior corneal tangential curvature were measured using a rotating Scheimpflug camera before and 1 week and 1 month after surgery. In 84 eyes of 42 cases, anterior and posterior corneal elevations and corneal thicknesses also were measured by scanning-slit topography before and 1 month after surgery., Main Outcome Measures: Time course of the ACV, ACD (central, midperiphery, periphery), corneal thickness, central corneal true net power, posterior corneal tangential curvature using the Scheimpflug camera, and amount of forward shifting of the posterior corneal surface at the center of the difference map using scanning-slit topography., Results: Preoperative and 1-month postoperative mean ACVs were 198.1 mm3 and 196.4 mm3, respectively, and preoperative and postoperative mean ACDs (center, midperiphery, periphery) were 3.24, 2.65, and 1.89 mm, and 3.21, 2.63, and 1.87 mm, respectively. The corneal thickness within the optical zone, subjective refraction, and central corneal true net power significantly changed by tissue subtraction after LASIK (P<0.0001). There were no significant differences in the ACV, ACDs (center, midperiphery, periphery), peripheral corneal thickness, and posterior corneal tangential curvature from preoperatively to 1 month after LASIK. However, using scanning-slit topography, the posterior corneal surface displayed a mean forward shift of 29.0+/-19.0 microm 1 month after surgery., Conclusion: The posterior corneal curvature, peripheral corneal thickness, ACDs, and ACV were consistent. These observations indicated that neither forward shifting of the central posterior corneal surface (bulging) nor backward shifting of the peripheral posterior corneal surface due to corneal swelling after ablation occurred after LASIK.

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.

Purpose: To investigate the efficacy of intraocular lens (IOL) implantation in reducing the incidence of postoperative retinal detachment after cataract surgery in patients with atopic dermatitis., Design: Retrospective review., Participants: One hundred sixty-nine eyes of 126 patients who underwent cataract surgery for atopic cataract were followed for more than 1 year. None of the eyes previously had a retinal detachment or retinal detachment surgery., Methods: The eyes were divided into 132 eyes of 95 patients with an IOL implantation (IOL group) and 37 eyes of 31 patients without an IOL implantation (aphakia group). The postoperative visual acuity and incidence of postoperative retinal detachment were compared between the 2 groups. The effects of the location of the causative retinal breaks, intraoperative posterior capsule rupture, and postoperative posterior capsulotomy on the incidence of retinal detachments were evaluated., Main Outcome Measures: The postoperative corrected visual acuity, incidence of postoperative retinal detachment, and influence of intraoperative posterior capsule rupture on the retinal detachment., Results: The final visual acuity was better than or equal to 20/20 in 128 eyes (97.0%) of the IOL group and in 29 eyes (78.4%) of the aphakia group (P = 0.0007). Retinal detachment after an uncomplicated cataract surgery occurred in 3 eyes (2.3%) of the IOL group and in 8 eyes (25.8%) of the aphakia group (P<0.0001, Mantel-Cox). Two of 3 eyes (66.7%) in the IOL group and 1 of 8 eyes (16.7%) in the aphakia group that later developed a retinal detachment had an intraoperative posterior capsule rupture. Posterior capsulotomy by yttrium-aluminum-garnet laser did not seem to alter the incidence of postoperative retinal detachment in either the IOL (2.0%) or the aphakia group (25.0%)., Conclusions: The rate of postoperative retinal detachment in eyes with IOL and no intraoperative posterior capsule rupture seems to be low. Intraocular lens implantation with capsular bag fixation may reduce the incidence of postoperative retinal detachment triggered by lens surgery for atopic cataract.

Purpose: To investigate the effect of periocular warming on accommodation amplitude and near vision after prolonged near work in visual display terminal (VDT) workers in an office setting., Design: Prospective interventional observational case series., Participants: Ten healthy Japanese male volunteers (mean age, 39.3+/-2 years [range, 36-43]) with a best distance corrected visual acuity (VA) of >20/20 who performed near work for 7 hours were included in the study., Main Outcome Measures: The differences of subjective and objective accommodations, near acuity, and pupil diameters were compared and studied in 2 experimental settings with and without periocular warming., Methods: Two experiments were performed on each subject on 2 different days. In one experiment, the subjects wore an eye mask and closed their eyelids for 10 minutes after 7 hours of VDT work (lid closure [LC] group). In the other experiment, the subjects applied warming sheets (WSs) to their eyelids and the periocular region and wore masks for 10 minutes again after 7 hours of VDT work (WS group). Visual display terminal work was performed under the same settings on both days. Subjective and objective accommodations, near vision, and pupil diameters were measured immediately before and immediately after the resting or warming procedure and again 90 minutes after the resting or warming procedures., Results: Fifty percent of eyes had an increase in the accommodation amplitude of at least 0.5 diopters immediately after application of the WSs. Forty percent of eyes still maintained the accommodation amplitude level at 90 minutes. The mean near logarithm of the minimum angle of resolution VA immediately after application of WSs and at 90 minutes significantly improved relative to the near acuity values after simple eyelid closure., Conclusion: Periocular warming was found to be associated with increases in subjective and objective accommodations, with a concomitant improvement in near VA. Periocular warming with disposable WSs is a simple and effective method of increasing near work-related ergonomy.

Objective: To evaluate the effect of autologous serum application for epithelial disorders in neurotrophic keratopathy (NK)., Design: Retrospective, noncomparative case series., Participants: Fourteen eyes of 11 patients with NK seen at Tokyo Dental College, Ichikawa General Hospital, Department of Ophthalmology, were studied., Intervention: Twenty percent topical autologous serum eye drops were applied 5 to 10 times daily until resolution of the NK. Patients underwent routine ophthalmic examinations, including slit-lamp examination, corneal fluorescein dye testing, Cochet-Bonnet corneal sensitivity (Luneau, France), and best-corrected visual acuity (BCVA) measurements before and at the end of the treatment. Moreover, serum samples from 10 healthy volunteers were studied for the levels of substance P (SP), insulinlike growth factor (IGF-1), and nerve growth factor (NGF) by using radioimmunoassay and enzyme-linked immunosorbent assay techniques. Tear samples from 3 healthy subjects also were analyzed for NGF and IGF-1 levels by the same techniques., Main Outcome Measures: The changes in corneal disease state, corneal sensitivity, and BCVA with treatment were evaluated. The levels of neural healing factors like SP, IGF-1, and NGF in serum as well as NGF and IGF-1 in tears of healthy subjects also were examined., Results: The epithelial disorders healed completely in all eyes within 6 to 32 days (mean, 17.1+/-8.0 days), with a decrease in corneal scarring. The mean pretreatment corneal sensitivity was 11.8+/-11.6 mm, which increased to 30.0+/-22.9 mm after treatment at the last follow-up. Five eyes attained normal corneal sensitivity with treatment. The BCVA improved by >2 Landolt lines in 78.6% of the eyes. The mean concentrations of SP in diluted and undiluted serum were 31.4+/-8.4 pg/ml and 157.0+/-42.1 pg/ml, respectively. The mean respective concentrations of IGF-1 in diluted and undiluted serum were 31.4+/-14.8 ng/ml and 157.0+/-73.9 ng/ml. The mean concentrations for NGF were 93.6+/-63.5 pg/ml and 468.3+/-317.4 pg/ml in serum samples with and without dilution, respectively. The mean concentration of NGF in tears was found to be 54 pg/ml. Insulinlike growth factor 1 was not detected in tears in this study., Conclusions: Autologous serum harbors neurotrophic factors. Autologous serum treatment may provide neural healers to the compromised ocular surface and seems promising for the restoration of the ocular surface epithelial integrity in patients with NK.

Objective: To describe the ocular surface and tear function findings in premature and term babies., Design: Prospective, case-control study., Participants: Forty-eight eyes of 24 premature babies seen at the Department of Ophthalmology of Uludag University School of Medicine, Bursa, Turkey, from March 2002 through September 2002 and 50 eyes of 25 healthy term babies were studied., Intervention: The subjects underwent routine ophthalmic examinations; corneal sensitivity measurements; Schirmer test with anesthesia, with and without nasal stimulation; primary Jones test; fluorescein staining of the ocular surface; and conjunctival impression cytology., Main Outcome Measures: Premature and term babies were compared for corneal sensitivity, lacrimal drainage system patency, tear function and ocular surface staining parameters, goblet cell density, and squamous metaplasia grade. The relation of these parameters to the status of the ocular surface was also investigated., Results: Mean corneal sensitivity scores were 45+/-5.0 mm and 55+/-4.5 mm in the premature and term babies, respectively (P<0.001). Premature babies had a mean corneal fluorescein staining score of 1.5+/-0.25 points, compared with 0.22+/-0.28 points in the term babies (P<0.001). The mean Schirmer test scores without and with stimulation were 1.5+/-2.5 mm and 4.15+/-2.5 mm in the premature babies, respectively, compared with 15+/-3.5 mm and 18.75+/-4.5 mm in the term babies. The intragroup and intergroup Schirmer test scores were statistically significant (P<0.001). The primary Jones test was positive in 20.8% of the eyes in the premature babies, whereas it was positive in 84% of eyes in the term babies. The premature babies with positive primary Jones test results all had corneal epithelial defects or severe superficial punctuate keratopathy. Mean conjunctival impression cytology squamous metaplasia scores were 1.86+/-1.2 in the premature babies and 0.86+/-0.47 in the term babies (P<0.001). Mean goblet cell densities were 393+/-484 cells/mm(2) and 739+/-503 cells/mm(2) in the premature and term babies, respectively (P<0.001)., Conclusion: Decreased corneal sensitivity, reduced tearing, and lacrimal drainage patency are important determinants of ocular surface disease in premature infants. Premature newborns with low Schirmer test scores and a patent lacrimal system may experience corneal and conjunctival epithelial problems and should be carefully checked for the presence of dry eye complications.

Purpose: To evaluate the effect of lacrimal punctal occlusion in the management of the ocular surface disease in chronic Stevens-Johnson syndrome., Design: Retrospective noncomparative case series., Participants: Thirty-one eyes of 18 patients with chronic Stevens-Johnson syndrome seen at the Department of Ophthalmology of the Tokyo Dental College were studied., Intervention: Patients' lacrimal puncta were occluded by cauterization or with punctal plugs., Main Outcome Measures: The effect of lacrimal punctal occlusion was evaluated by changes in subjective symptoms, best-corrected visual acuity (VA), Schirmer test, tear clearance test, and ocular surface double vital staining before and after punctal occlusion., Results: After lacrimal punctal occlusion, symptomatic improvement was observed in 19 eyes (61.3%). The mean logarithmic VA showed significant improvement from -0.64+/-0.87 to -0.52+/-0.86 (P<0.05). The Schirmer I test results before punctal occlusion yielded a mean score of 7.4+/-8.7 mm, which changed to 10.2+/-8.3 mm after punctal occlusion. The mean preocclusion and postocclusion tear clearance values were 7.5+/-6.6 times and 4.9+/-4.8 times, respectively. The Rose Bengal staining score decreased from 4.7+/-2.8 to 2.7+/-2.2 points (P<0.05), and the fluorescein staining score decreased from 5.0+/-2.3 to 2.2+/-2.5 points (P<0.05), respectively., Conclusions: Concurrent improvements in subjective symptoms, vital staining scores, and VA point to the favorable effects of lacrimal punctal occlusion for the ocular surface health in chronic Stevens-Johnson syndrome.

Purpose: To study the association between surgical approach and postoperative results in chemical and thermal burns of the cornea., Design: Retrospective, interventional, noncomparable case series., Participants: Thirty-two eyes of 32 patients with chemical (n = 27) or thermal (n = 5) burns of the cornea that were associated with total limbal dysfunction. Eight eyes had a history of previous keratoplasty., Intervention: Patients were treated by amniotic membrane transplantation combined with either conjunctivolimbal autograft transplantation (autograft group, n = 11) or keratolimbal allograft transplantation (allograft group, n = 21). Fifteen eyes had simultaneous penetrating keratoplasty (simultaneous group), and 6 had keratoplasty several months after ocular surface reconstruction (2-step group)., Main Outcome Measures: Reconstruction of the corneal surface by corneal epithelium, clarity of the cornea, and incidence of postoperative complications. The outcome was compared between the autograft and allograft groups and also between the simultaneous and 2-step groups., Results: At final examination, 17 eyes (53.1%) showed stable corneal epithelialization. Preoperative conditions were similar in the autograft and allograft groups and also in the simultaneous and 2-step groups. The autograft group showed significantly better results than the allograft group in both corneal epithelialization (Kaplan-Meier analysis, P = 0.003) and clear cornea (P = 0.010). Although the incidences of corneal epithelialization and clear corneas did not significantly differ between the simultaneous and 2-step groups, the former had a higher rate of endothelial rejection in the central graft (P = 0.019)., Conclusions: In chemical or thermal burns of the cornea with monocular involvement, autografting should be considered as a first choice of surgery. Even in eyes with opaque corneal stroma, it may be safer to perform ocular surface reconstruction first, followed by keratoplasty as a secondary procedure.

Purpose: To describe the ocular surface disorder in patients with keratoconus., Design: A prospective, case-controlled study., Participants: Seventy-five eyes of 38 patients with keratoconus seen at Uludag University School of Medicine, Department of Ophthalmology, from March 2000 through April 2001, and 80 eyes of 40 normal control subjects were studied., Intervention: The subjects underwent routine ophthalmic examinations, corneal sensitivity measurements, Schirmer test, tear film breakup time (BUT), fluorescein and rose bengal staining of the ocular surface, and conjunctival impression cytology., Main Outcome Measures: Patients and control subjects were compared for corneal sensitivity, tear function, ocular surface staining parameters, goblet cell density, and squamous metaplasia grade. The relation of these parameters to the severity of keratoconus progression was also investigated., Results: The mean corneal sensitivity was significantly lower in keratoconus patients compared with control subjects (P < 0.001). The BUT values were also significantly lower in the keratoconus group. Patients with keratoconus had significantly higher fluorescein and rose bengal staining scores (P < 0.001). Corneal sensitivity and tear function changes seemed to get worse with advanced stages of keratoconus. Impression cytology showed goblet cell loss and conjunctival squamous metaplasia, both of which again related to the extent of progression of keratoconus., Conclusions: The ocular surface disease in keratoconus is characterized by disorder of tear quality, squamous metaplasia, and goblet cell loss, all of which seem to relate to the extent of keratoconus progression.

Objective: To study the effect of amniotic membrane transplantation (AMT) combined with either limbal autograft transplantation (LAT) or conjunctival autograft transplantation (CAT) in recurrent pterygium., Design: Retrospective, noncomparative, interventional case series., Participants: Twenty-seven eyes of 27 patients with recurrent pterygium. The mean number of prior surgeries was 3.1 (range, 1-10). Fifteen eyes each had restriction of ocular movement and symblepharon before surgery., Intervention: Patients were treated by AMT with either LAT (n = 15) or CAT (n = 12)., Main Outcome Measures: Recurrence of pterygium, improvement in ocular movement, and symblepharon formation., Results: Twenty-three (85.2%) of 27 eyes showed no recurrence with a mean observation period of 67.0 weeks. Fourteen eyes (93.3%) each showed improvement in ocular movement restriction and symblepharon after AMT. In four eyes that developed recurrence, three had LAT and one had CAT combined with AMT, suggesting that there was no difference in surgical outcome between LAT and CAT., Conclusions: AMT with CAT is a safe and effective method for recurrent pterygium, especially that associated with ocular movement restriction and symblepharon. Considering the potential adverse effects associated with limbal excision, AMT plus CAT may be preferred over AMT plus LAT.

Objective: We developed low-concentration homogenized castor oil eye drops for the treatment of patients with noninflamed obstructive meibomian gland dysfunction (MGD), a major cause of lipid-deficiency dry eye, and assessed the safety, stability, and efficacy of the eye drops., Design: Randomized, double-masked, placebo-controlled crossover clinical trial., Participants: Forty eyes of 20 patients with noninflamed MGD., Methods: After a preliminary study of eye drops containing castor oil, 2% castor oil and 5% polyoxyethylene castor oil (emulsifier) were mixed to formulate homogenized oil eye drops. The patients were assigned randomly to receive oil eye drops or placebo six times daily for 2 periods of 2 weeks each., Main Outcome Measures: At the end of each treatment period, we assessed symptoms, tear interference grade, tear evaporation, fluorescein and rose bengal scores, tear break-up time (BUT), and meibomian gland orifice obstruction. Safety and stability tests were also performed., Results: Symptom scores, tear interference grade, tear evaporation test results, rose bengal scores, tear BUT, and orifice obstruction scores after the oil eye drop period showed significant improvement compared with the results after the placebo period. No complications attributable to the eye drops were observed. The oil eye drops were stable when stored at 4 degrees C., Conclusions: The results indicate that castor oil eye drops are effective and safe in the treatment of MGD. The possible mechanisms of this treatment are improvement of tear stability as a result of lipid spreading, ease of meibum expression, prevention of tear evaporation, and the lubricating effect of the oil eye drops.

Purpose: To study the short-term clinical results of transplanting of cultivated corneal/limbal epithelial cells on human amniotic membrane (AM) for limbal deficiency., Design: Noncomparative, retrospective interventional case series., Participants: Thirteen eyes of 13 patients with severe limbal deficiency (Stevens-Johnson syndrome in eight eyes, ocular cicatricial pemphigoid in three eyes, and chemical burns in two eyes) were treated at the department of Ophthalmology, Tokyo Dental College, Japan., Intervention: Cultivated allo-limbal epithelium was transplanted onto the ocular surface of patients with severe limbal deficiency., Main Outcome Measures: Ocular surface reconstruction with corneal epithelialization, changes in visual acuity, and postoperative complications were studied. Histologic examinations were also performed on cultivated epithelium., Results: Cultivated corneal epithelium on AM formed two to three layers with the formation of basement membrane-like structures. After the surgery, the epithelium regenerated and covered the ocular surface in eight eyes (61.5%). However, three of the eight eyes developed partial conjunctival invasion, and two eyes later developed epithelial defects. At last examination, corneal epithelialization was achieved in six eyes (46.2%). Five eyes had conjunctivalization, one eye had dermal epithelialization, and one eye was not epithelialized. Complications were corneal perforation in four eyes and infectious keratitis in two eyes., Conclusions: This study demonstrates that the success rate for transplanting cultivated allo-limbal epithelium on the AM is not different from the conventional limbal and AM transplantation for the treatment of severe limbal stem cell dysfunction.

Objective: To retrospectively study the surgical outcome in severe Stevens-Johnson syndrome (SJS)., Design: Retrospective noncomparative case series., Participants: Twenty-nine eyes of patients with severe SJS associated with total conjunctivalization were examined., Intervention: Preserved human amniotic membrane grafting and keratolimbal allograft transplantation was performed. Intensive immunosuppression and epithelial management were continued postoperatively., Main Outcome Measures: Successful ocular surface reconstruction was determined by epithelialization with corneal epithelium. The association between surgical outcome and preoperative tear function was studied., Results: The ocular surface was successfully covered by corneal epithelium in 13 eyes (44.8%). The mean corrected visual acuity recovered from 0.0039 to 0.017. Persistent epithelial defect was the most common complication. Eyes with successful ocular surface reconstruction had significantly better preoperative Schirmer's test values (P = 0.025) and tear clearance rates (P = 0.043) than those that failed., Conclusions: In patients with severe SJS, preoperative tear function significantly influenced surgical outcome. Eyes with Schirmer's test value of >10 mm have a greater chance of successful ocular surface reconstruction.

Objective: To evaluate the efficacy of autologous serum application for the treatment of persistent epithelial defect., Design: Prospective, clinical, noncomparative case series., Participants: A total of 16 eyes were studied., Intervention: Autologous serum was prepared from the patients and diluted to 20% by saline. The patients were instructed to use the autologous serum six to ten times a day. The concentration of vitamin A, epidermal growth factor (EGF), and transforming growth factor-beta (TGF-beta) was measured at 1 week and 1 month stored in the refrigerator and 1 month and 3 months in the freezer., Main Outcome Measures: Time to closure of epithelial defect., Results: Vitamin A, EGF, and TGF-beta were stable during the 1 month in the refrigerator and 3 months in the freezer. Among 16 persistent epithelial defects, 7 (43.8%) healed within 2 weeks, 3 (18.8%) healed within 1 month, and the remaining 6 (37.5%) did not respond within 1 month. No apparent side effect of autologous serum application was observed., Conclusions: Autologous serum application healed 43.8% of persistent defect within 2 weeks and 62.5% within 1 month.

Objective: Changes in the ocular surface of patients with Sjögren syndrome (SS) often are more severe than those in patients with dry eye without SS. This study was conducted to investigate the possible involvement of meibomian gland dysfunction in SS-related ocular surface abnormalities., Design: A nonrandomized, prospective, clinical study., Participants: Twenty-seven eyes of 27 consecutive patients with SS (SS group) were studied. Twenty-nine eyes of age- and gender-matched non-SS patients with aqueous tear deficiency (non-SS group) were examined as control subjects., Intervention: Changes in the ocular surface, tear function, and meibomian gland were examined., Main Outcome Measures: Tear evaporation rate, meibomian gland expression, and meibography were measured., Results: Fluorescein and rose bengal staining scores were significantly higher in the SS group than in the non-SS group (P = 0.0001). Evaporation of tears was increased significantly in the SS group compared with the non-SS group. There were no significant differences in the rate of tear production between the SS and non-SS groups. Meibography showed that 11 (57.9%) of 19 eyes in the SS group had gland dropout (i.e., histologic destruction of meibomian glands) in more than half of the tarsus. The incidence was significantly higher than that in the non-SS group (5 [18.5%] of 27 eyes; P = 0.005)., Conclusions: The results of this study indicate that destruction of meibomian glands and an increase in tear evaporation often are associated with changes in the ocular surface in patients with SS. Severe ocular surface changes in patients with SS may be attributed, in part, to the meibomian gland dysfunction.

Objective: Previous studies have shown that removal of running sutures after penetrating keratoplasty causes unpredictable changes in astigmatism. The current study was conducted to investigate whether computer-assisted videokeratography is beneficial for predicting visual outcomes after running sutures are removed., Design: The design was that of a prospective clinical study., Participants: The authors prospectively studied 29 consecutive eyes undergoing a 10-0 nylon running suture removal after penetrating keratoplasty., Interventions: Videokeratography was performed before, 1 week, 1 month, and 3 months after removal of sutures., Main Outcome Measures: Changes in refractive and topographic astigmatism after suture removal were measured. Topographic patterns and their quantitative descriptors also were analyzed., Results: An asymmetric bowtie was the most common videokeratography pattern both before and after suture removal. After suture removal, the incidence of peripheral corneal steepening increased significantly (2 vs. 21 eyes, P < 0.0001), and that of focal flattening of the midperipheral cornea decreased (13 vs. 5 eyes, P = 0.046). The mean topographic astigmatism, surface regularity index, and corrected visual acuity were improved significantly by suture removal in eyes that had localized flattening but not in eyes without this finding. Eyes having either skewed axis in astigmatism or topographic astigmatism of more than 9 diopters also showed significant decreases in astigmatism., Conclusions: Suture removal after keratoplasty is advantageous for both reducing astigmatism and normalizing topography, especially in eyes that have localized flattening of the midperipheral cornea. Predictability of visual outcomes of a running suture removal in postkeratoplasty eyes may be improved by the use of videokeratography.

Objective: The purpose of the study is to examine the usefulness of preserved human amniotic membrane transplantation in patients with chemical and thermal burns., Design: The study design was a nonrandomized clinical trial., Participants: Seven eyes of six patients with severe chemical (n = 5) and thermal (n = 2) burns were studied., Intervention: Eyes were treated with excision of cicatricial tissues followed by a placement of amniotic membrane on the sclera. Transplantation of limbal grafts from an opposite eye (n = 4) or from donor eyes preserved at -80 degrees C (n = 2) was performed simultaneously., Main Outcome Measures: Reconstruction of ocular surface epithelia and visual acuity were measured., Results: With the mean observation period of 53.3 weeks, central corneal epithelium was reconstructed successfully in all eyes. Neither amniotic membrane nor limbal grafts were rejected. A persistent epithelial defect developed in one eye, which was treated successfully by tarsorrhaphy. After surgery, the corneal epithelium showed normal arrangements on specular microscopy, and its barrier function recovered to seminormal. Corrected visual acuity markedly improved in each eye. Regenerated conjunctiva on the amniotic membrane was stable and uninflammed with minimum-to-mild scarring. Slight recurrence of conjunctivalization was noted in three eyes. However, because these eyes were stable and central cornea was clear, no further surgery was needed., Conclusions: Amniotic membrane transplantation promotes normal conjunctival epithelialization while suppressing fibrosis formation. The procedure, especially when performed with limbal autograft transplantation, appears to be effective for the treatment of chemical or thermal burns of the ocular surface.

Purpose: To investigate prospectively the effect of diclofenac sodium (DfNa) eye drops on corneal epithelial structure and function., Methods: Seventeen patients with bilateral age-related cataract undergoing phacoemulsification combined with intraocular lens implantation were studied prospectively. After the surgery on both eyes, one eye each of these patients was assigned randomly to receive 0.1% DfNa eye drops three time daily (DfNa group), and the other eye served as control (control group). Vital stainings, tear function test, corneal sensitivity measurement, specular microscopy for corneal epithelium and endothelium, pachymetry, anterior fluorometry to measure epithelial barrier function, and laser flare-cell-metry were performed before and after surgery., Results: There were no statistically significant differences between the DfNa and control groups in any measurement examined except for laser cell-flare-metry, in which the DfNa group demonstrated a significantly lower flare value at day 7 postoperatively (compare with the preoperative level of 73% +/- 41% in the DfNa group, and 130% +/- 98% in the control group, P=0.035). Epithelial cells in the DfNa group showed slight elongation and increased permeability postoperatively; however, there were no statistically significant differences with the control group., Conclusions: Administration of DfNa eye drops did not cause significant abnormalities in the corneal epithelial structure or function of patients who had undergone small-incision cataract surgery. Their safety for use in procedures such as excimer laser photorefractive keratectomy remains to be established.

Purpose: Although penetrating keratoplasty is an established surgical procedure, it often is ineffective for severe ocular surface diseases such as alkali burns or limbal deficiency. The authors have performed limbal allograft transplantation for the reconstruction of the corneal epithelium., Methods: A total of nine patients (3 with chemical injury, 3 with limbal deficiency with unknown etiology, 2 with moderate ocular pemphigoid [OCP], and 1 with traumatic limbal deficiency) were treated by limbal allograft transplantation. Penetrating keratoplasties were performed in all patients with the exception of one with OCP. Patients received cyclosporine both systemically (10 mg/kg) and topically (0.05%) as well as high-dose intravenous dexamethasone (8 mg)., Results: The corneal epithelium was reconstructed in all patients, although two showed partial increased fluorescein permeability and two others required a second surgery. The other five epithelia remained clear at mean follow-up of 12.3 months, with two episodes of graft rejection which were controlled successfully by medication., Conclusions: Limbal allograft transplantation with intensive immunosuppression by cyclosporine and high-dose steroids appears to be a promising surgical intervention for the reconstruction of corneas affected by severe ocular surface disease.

Purpose: The authors' clinical experience has suggested that there is a form of dry eye with only decreased tear break-up time, which is associated with allergic conjunctivitis. The current study was performed to verify this hypothesis., Method: The authors recruited patients with two types of dry eye syndrome, those with only decreased tear break-up (BUT type) and those with positive vital staining (staining type). Individuals without any symptoms or signs served as controls. All subjects were compared regarding symptoms, Schirmer and tear clearance test results, conjunctival papillary formation, antigen-specific serum-IgE level (s-IgE), and goblet cell density of the palpebral conjunctiva. Antigen-induced allergic conjunctivitis was produced in guinea pigs, and histopathologic changes of the conjunctiva were examined., Results: Patients with the BUT-type dry eye syndrome were younger and their symptoms were as severe as the staining type. The Schirmer and tear clearance test results were better, and the papillary formation and s-IgE were observed more than in the BUT type. The average goblet cell density in the BUT-type syndrome was 625.4 +/- 193.2/mm2, which was significantly less than 1005.6 +/- 294.5/mm2 in the controls (P < 0.01). The average goblet cell density was significantly decreased in the allergic animals (10.40 +/- 1.11/0.2 mm) compared with that of the controls (16.21 +/- 0.26/0.2 mm) or the anti-allergic drug-treated group (13.69 +/- 0.30/0.2 mm) (P < 0.01)., Conclusion: These results support the authors' hypothesis that decreased break-up time is in part associated with the decreased goblet cell density caused by allergic conjunctivitis.

Purpose: To investigate the clinical course of patients with familial subepithelial amyloidosis of the cornea (FSA)., Methods: The authors retrospectively investigated the clinical course of seven Japanese patients with FSA. Corneal specimens obtained at the time of keratoplasty were examined histopathologically., Results: The mean follow-up period was 20.6 years, including four patients followed for more than 25 years. In all patients, the initial symptoms of photophobia and epiphora started in the first decade of life. All except one patient had their first keratoplasty before 30 years of age. The seven Japanese patients with FSA had a total of 35 keratoplasties, each of which was followed by a severe recurrence of disease. In each patient, subepithelial haziness developed in the graft within 1 year of keratoplasty (mean, 7.9 months). Amyloid deposition typically recurred within a few years (mean, 26.6 months) followed by a deterioration of vision. There was a high incidence of postkeratoplasty complications such as wound dehiscence, glaucoma, and cataract. Histopathologic findings demonstrated that, in the early phase of recurrence, amyloid was deposited between the basal cell of the epithelium and Bowman's layer., Conclusion: Patients with FSA have ocular symptoms with a deterioration in vision from an early decade of life. Conventional surgical approaches were complicated by subepithelial haziness in the first postoperative year, which was followed by a severe recurrence in each patient. New surgical approaches may be indicated in FSA.

Purpose: Although the combination of a hard contact lens "piggybacked" on a soft lens base for the correction of severe astigmatism in keratoconus has existed for two decades, little is known about its effect on the corneal epithelium and endothelium. This study involves two parts: the measure of oxygen pressure in rabbits, and the long-term effects on patients with keratoconus wearing these hybrid lenses., Methods: A polarographic sensor was used to measure the oxygen pressure on rabbit corneas under two types of piggyback lenses: oxygen-permeable hard lenses on high water-content soft lenses, and polymethylmethacrylate (PMMA) lenses on low water-content soft lenses. In the clinical evaluation, 11 patients with keratoconus (8 men, 3 women; 25.1 +/- 4.9 years of age) who could not wear hard contact lenses due to constant pain or inadequate lens fitting were given oxygen-permeable piggyback contact lenses and were observed for at least 9 months., Results: In the animal study, the oxygen pressure under piggybacked oxygen-permeable hard contact lenses was 95 +/- 14 mmHg after 5 minutes wear, but it was only 34 +/- 14 mmHg when PMMA and low water-content lenses were used. Ten of 11 patients were successfully treated using this technique, whereas one patient had persistent contact lens loss, requiring penetrating keratoplasty. Specular microscopic observation of the corneal epithelium and endothelium did not show any changes during the follow-up period., Conclusions: These results suggest the efficacy and safety of the piggyback combination of oxygen-permeable hard and soft contact lenses for the correction of astigmatism in patients with keratoconus.