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Symptom overlap between meibomian gland dysfunction (MGD) and dry eye (DE) makes it difficult to distinguish between these two conditions on the basis of symptoms alone. We searched for characteristic symptoms that might help to distinguish MGD from DE on the basis of a population-based study. Subjects comprised 311 residents of Takushima island (18 to 96 years), including 117 individuals with MGD and 114 with DE. Responses to a symptom-related questionnaire (19 items) were subjected to factor analysis, and univariate regression analysis was performed to identify ocular surface parameters associated with characteristic symptoms of MGD. Factor analysis revealed aggregation of symptoms according to three factors: Factor 1 related to Symptom Score, Factor 2 to DE, and Factor 3 to MGD. Symptoms associated with DE included 11 items, whereas the only item related to MGD was tearing sensation. Pearson’s correlation analysis revealed that tearing sensation was associated with tear meniscus height (TMH), noninvasive tear-film breakup time, fluorescein staining score, meiboscore, meibum grade, and Schirmer value. Subjects with MGD experienced significantly more tearing and had a larger TMH than did those without MGD (p = 0.0334). Tearing sensation may thus be a characteristic symptom of MGD. Physicians should suspect MGD who complain of tearing sensation.

Purpose To evaluate the prevalence and risk factors of and the relationship between meibomian gland dysfunction (MGD) and dry eye (DE) in Japan. Design A population-based cross-sectional study. Methods Participants filled in questionnaires regarding ocular symptoms, systemic diseases, and lifestyle factors. Meibomian gland-related parameters and tear film-related parameters were evaluated. Risk factors for MGD and DE were analyzed by using univariate and multivariate logistic regression. Age-specific prevalence of MGD and DE was estimated by using a general additive model with degree-3 natural splines. The structural relation between MGD and DE was assessed by factor analysis using the principal components method and promax rotation. Results A total of 356 residents of Takushima Island (133 males, 223 females) at the mean ± SD age of 55.5 ± 22.4 years (range, 6-96 years) were enrolled. The prevalence of MGD and DE was 32.9% and 33.4%, respectively, with a coexistence rate of 12.9%. The prevalence of MGD was associated with male sex (odds ratio [OR], 2.42), age (OR per decade increment,1.53), and oral intake of lipid-lowering agents (OR, 3.22). The prevalence of DE was associated with female sex (OR, 3.36), contact lens wear (OR, 2.84), conjunctivochalasis (OR, 2.57), and lid margin abnormalities (OR, 3.16). The age-specific prevalence of MGD and DE differed, and factor analysis for 16 parameters showed that MGD and DE had independent hidden sources (interfactor correlation, −0.017). Conclusions MGD and DE are common in this population. Although their ocular symptoms are similar, the pathogenesis of MGD differs from that of DE.

Background: To develop a prediction formula for best corrected visual acuity with hard contact lenses (HCL-BCVA) and to identify clinical factors linearly related to HCL-BCVA in keratoconus patients. Methods: This retrospective study examined clinical data derived from 198 eyes of 131 keratoconus patients. The subjects were divided into a development group (102 eyes of 68 subjects) and a validation group (96 eyes of 63 subjects) on the basis of the date of their examination. HCL-BCVA measurement and anterior segment–optical coherence tomography (AS-OCT) were performed. A prediction formula for HCL-BCVA based on AS-OCT measurements was then developed. Single regression analysis was performed to identify clinical factors linearly related to HCL-BCVA. Results: Stepwise multiple regression analysis yielded a prediction formula for HCL-BCVA in keratoconus patients, with the correlation coefficient of the multiple regression equation being 0.728 (R2 = 0.530) for the development group. Application of the prediction formula to the validation group yielded a correlation coefficient for the multiple regression equation of 0.641 (R2 = 0.411). Single regression analysis identified anterior corneal refractive power, posterior corneal refractive power, and high-order aberrations as factors that are linearly correlated with HCL-BCVA, with R values of 0.606, -0.617, and 0.506, respectively. Conclusion: HCL-BCVA in keratoconus patients was predictable on the basis of AS-OCT measurements. Cutoff values for clinical factors found to correlate with HCL-BCVA may prove informative with regard to treatment options to maintain a favorable visual acuity in keratoconus patients.

Detection of refractive error in children is crucial to avoid amblyopia and its impact on quality of life. We here performed a retrospective study in order to develop prediction models for spherical and cylinder refraction in children. The enrolled 1221 eyes of 617 children were divided into three groups: the development group (710 eyes of 359 children), the validation group (385 eyes of 194 children), and the comparison group (126 eyes of 64 children). We determined noncycloplegic and cycloplegic refraction values by autorefractometry. In addition, several noncycloplegic parameters were assessed with the use of ocular biometry. On the basis of the information obtained from the development group, we developed prediction models for cycloplegic spherical and cylinder refraction in children with the use of stepwise multiple regression analysis. The prediction formulas were validated by their application to the validation group. The similarity of noncycloplegic and predicted refraction to cycloplegic refraction in individual eyes was evaluated in the comparison group. Application of the developed prediction models for spherical and cylinder refraction to the validation group revealed that predicted refraction was significantly correlated with measured values for cycloplegic spherical refraction (R = 0.961, P < 0.001) or cylinder refraction (R = 0.894, P < 0.001). Comparison of noncycloplegic, cycloplegic, and predicted refraction in the comparison group revealed that cycloplegic spherical refraction did not differ significantly from predicted refraction but was significantly different from noncycloplegic refraction, whereas cycloplegic cylinder refraction did not differ significantly from predicted or noncycloplegic values. Our prediction models based on ocular biometry provide estimates of refraction in children similar to measured cycloplegic spherical and cylinder refraction values without the application of cycloplegic eyedrops.

Aqueous-deficient dry eye (ADDE) and meibomian gland dysfunction (MGD) can be refractory to therapy. Intense pulsed light (IPL) was recently introduced as an effective treatment for MGD. We here evaluated the efficacy of IPL combined with MG expression (MGX) compared with MGX alone (n = 23 and 20, respectively) for patients with refractory ADDE with mild MGD at three sites. Symptom score, visual acuity (VA), noninvasive breakup time (NIBUT) and lipid layer thickness (LLT) of the tear film, lid margin abnormalities, fluorescein BUT (FBUT), fluorescein staining, tear meniscus height (TMH), meibum grade, meiboscore, and Schirmer&rsquo, s test value were assessed at baseline and 1 and 3 months after treatment. LLT, plugging, vascularity, FBUT and NIBUT were improved only in the IPL-MGX group at three months compared with baseline. All parameters with the exception of VA, meiboscore, TMH, Schirmer&rsquo, s test value were also improved in the IPL-MGX group compared with the control group at three months, as was VA in patients with central corneal epitheliopathy. Although IPL-MGX does not affect aqueous layer, the induced improvement in quality and quantity of the lipid layer may increase tear film stability and ameliorate symptoms not only for evaporative dry eye but for ADDE.

Background/aim During screening for compounds that selectively suppress growth of human colorectal cancer (CRC) spheroids with mutant (mt) KRAS, the uridine analogue, 5-bromouridine (BrUrd) was identified and its derivatives were explored. Materials and methods DNA incorporation in two-dimensional (2D) and three-dimensional floating (3DF) cultures was examined with the uridine analogue, 5-ethynyl-2'-deoxyuridine (EdU). The area of HKe3 CRC spheroids expressing wild type (wt) KRAS (HKe3-wtKRAS) and mtKRAS (HKe3-mtKRAS) were measured in 3DF culture with 11 BrUrd derivatives. Results EdU was strongly incorporated into newly-synthesized DNA from HKe3-mtKRAS cells compared to HKe3-wtKRAS in 2D and 3DF culture. 3-Deaza-cytarabine, which has properties of BrUrd and cytidine, was the most effective inhibitor of HKe3-mtKRAS spheroids with the least toxicity to HKe3-wtKRAS. Growth suppression of 3-deaza-cytarabine was stronger than cytarabine in 2D culture, and toxicity was lower than gemcitabine in long-term 3DF culture. Conclusion 3-Deaza-cytarabine exhibits properties useful for the treatment of CRC patients with mtKRAS.

Purpose: To evaluate the efficacy of intense pulsed light (IPL) therapy combined with meibomian gland expression (MGX) for refractory meibomian gland dysfunction (MGD) in a prospective study conducted at 3 sites in Japan. Methods: Patients with refractory obstructive MGD were enrolled and underwent 4 to 8 IPL-MGX treatment sessions at 3-week intervals. Clinical assessment included the Standard Patient Evaluation of Eye Dryness questionnaire; noninvasive breakup time of the tear film and interferometric fringe pattern as determined by tear interferometry; lid margin abnormalities, fluorescein breakup time of the tear film, corneal and conjunctival fluorescein staining (CFS), and meibum grade as evaluated with a slit-lamp microscope; meibomian gland morphology (meiboscore); and tear production as measured by the Schirmer test without anesthesia. Results: Sixty-two eyes of 31 patients (17 women, 14 men; mean age ± SD, 47.6 ± 16.8 years) were enrolled. The Standard Patient Evaluation of Eye Dryness score (P < 0.001), noninvasive breakup time (P < 0.001), and interferometric fringe pattern (P < 0.001) were significantly improved after therapy, with 74% of eyes showing a change in the interferometric fringe pattern from 1 characteristic of lipid deficiency to the normal condition. Meibum grade, lid margin abnormality scores, fluorescein breakup time, and CFS were also significantly improved (P < 0.001, P < 0.001, P < 0.001, and P = 0.002, respectively) after treatment, whereas the meiboscore and Schirmer test value remained unchanged. Conclusions: IPL-MGX ameliorated symptoms and improved the condition of the tear film in patients with refractory MGD and is therefore a promising treatment option for this disorder.

Meibomian glands secrete lipids (meibum) that form the surface lipid layer of the tear film and thereby prevent excessive evaporation of tear fluid. Meibomian gland dysfunction is a major cause of evaporative dry eye, which is more prevalent than aqueous-deficient dry eye. Noninvasive meibography with infrared light and an infrared charge-coupled device camera can detect morphological changes of meibomian glands in both upper and lower eyelids, whereas tear interferometry allows qualitative and quantitative evaluations of the lipid layer of the tear film. Such assessment of meibomian gland morphology provides clinical information that contributes to the diagnosis of evaporative dry eye, whereas that of the lipid layer of the tear film allows the monitoring of meibomian gland function. In addition, the balance between the lipid and aqueous layers of the tear film revealed by tear interferometry has provided both support for the operation of a compensatory system that maintains tear film homeostasis as well as insight into the pathophysiology of dry eye.

Meibomian glands secrete meibum, which gives rise to the lipid layer of the tear film and thereby prevents excessive evaporation of tear fluid. Meibomian gland dysfunction (MGD) is a major causative condition of evaporative dry eye, which is more common than the aqueous-deficient type of dry eye. Noninvasive meibography relies on infrared light and an infrared-sensitive camera to reveal the morphology of meibomian glands in both the upper and lower eyelids, whereas tear interferometry allows both qualitative and quantitative evaluation of the lipid layer of the tear film. These two techniques not only provide valuable clinical information related to dry eye but also allow clinical evaluation of MGD. Tear interferometry also has the potential to distinguish the condition of the tear film between normal individuals and dry eye patients. Furthermore, combined evaluation of the noninvasive breakup time of the tear film and the interferometric fringe pattern as determined by tear interferometry allows classification of the subtype of dry eye disease.

Purpose: We measured tear film parameters, including the morphology and function of meibomian glands, in junior high school students at 15 years of age. Methods: A total of 111 eyes of 111 students (56 males and 55 females) were enrolled in the study. The ocular symptom score (0–14), after-school study time, lipid layer thickness (LLT) of the tear film, partial blink rate, lid margin abnormalities (0–4), tear film breakup time, corneal and conjunctival epithelial damage (fluorescein staining score, 0–9), meiboscore as determined by noncontact meibography (0–6), Schirmer test value, and meibum grade (0–3) were determined. The relationships between parameters were evaluated with the Spearman correlation coefficient (ρ). Results: The meiboscore was 2.8 ± 1.2, and the meibum grade was 1.8 ± 1.2. The meiboscore significantly correlated with the meibum grade (ρ = 0.272, P = 0.004), Schirmer test value (ρ = −0.220, P = 0.021), and LLT (ρ = −0.264, P = 0.005). The breakup time significantly correlated with LLT (ρ = 0.261, P = 0.006), meibum grade (ρ = −0.338, P < 0.001), and fluorescein staining score (ρ = −0.214, P = 0.025). The partial blink rate significantly correlated with the Schirmer test value (ρ = −0.240, P = 0.011). The meiboscore (P < 0.001) and meibum grade (P = 0.032) were significantly greater in males than in females. Conclusions: The morphology and function of meibomian glands are altered even at 15 years of age, with the changes being more prominent in males than in females.

Purpose To provide insight into the mechanism underlying corneal deformation in keratoconus, we examined the relations among corneal curvature, thickness, and volume as well as the association of corneal scar formation with these parameters. Methods A total of 288 corneas of 174 keratoconus patients and 114 corneas of 57 control subjects were examined by anterior segment-optical coherence tomography (AS-OCT). Anterior and posterior refractive values, corneal thickness (CT), and corneal volume (CV) were determined by AS-OCT for both control and keratoconic eyes. The pattern of corneal stromal scarring was also determined from the AS-OCT images. Results The distribution of CV was similar for keratoconic and control eyes, whereas anterior and posterior refractive values as well as CT showed a wider distribution for keratoconic eyes. The progression of corneal deformation initially occurred without corneal thinning but was later associated with a decrease in CT and an eventual loss of CV. The progression of scarring from the anterior to the posterior stroma was associated with an increase in anterior refractive value and decreases in posterior refractive value, CT, and CV. Conclusions The progression of keratoconus as reflected by corneal deformation was associated with a reduction in CT and CV as well as stromal scar formation. The loss of CV occurred after the initial decline in CT, suggesting that stromal degradation occurred only at the advanced stage of keratoconus.

Purpose To develop and assess a method for quantitation of lower tear meniscus height (TMH) with the Kowa DR-1α tear interferometer. Methods Sixty-nine eyes of 49 men and 20 women (36 healthy volunteers, 33 patients with aqueous-deficient dry eye [ADDE]; mean age ± SD, 50.0 ± 14.0 years) were enrolled. TMH of each subject was measured by two observers both with DR-1α and newly developed software and with anterior-segment swept-source optical coherence tomography (SS-OCT). Intraoperator repeatability and interoperator and intersession reproducibility of measurements were assessed based on the within-subject SD (Sw), coefficient of variation (CV), and intraclass correlation coefficient (ICC). Agreement between the two devices was assessed by regression and Bland-Altman analysis. Results The CV for system repeatability of DR-1α was

Meibomian glands are located in the eyelids and secrete meibum, which gives rise to the lipid layer of the tear film. Changes to these glands can lead to the development of meibomian gland dysfunction (MGD), which is associated with various ocular symptoms such as fatigue, dryness, burning sensation, and heavy sensation. The diagnosis of MGD thus relies on evaluation of ocular symptoms, meibum condition, and lid margin abnormalities. The recent development of noninvasive meibography and tear interferometry has provided important insight into meibomian gland structure and function, respectively. Wearers of contact lenses complain of ocular symptoms that are thought to be attributable to a variety of causes, such as a diminished aqueous or mucin layer of the tear film, changes in tear protein concentration, and altered meibomian gland structure or function. Many studies have examined the relation between contact lens wear and meibomian gland changes. Such studies have found that lens wear is associated with adverse changes in meibomian gland morphology and in the condition of the lid margin and meibum, suggesting that contact lenses negatively affect meibomian glands. Meibomian gland dysfunction-like changes in meibomian glands induced by contact lens wear may thus be responsible for at least some of the ocular symptoms in lens wearers.

To investigate the clinical characteristics of viral endotheliitis after keratoplasty, we evaluated clinical parameters in individuals with anterior chamber inflammation after keratoplasty classified according to the absence or presence of DNA from various viruses in aqueous humor.A total of 29 eyes of 27 subjects with anterior chamber inflammation after keratoplasty were enrolled in the study. The subjects were classified into the herpes simplex virus (HSV) group (7 patients, 8 eyes), cytomegalovirus (CMV) group (6 patients, 6 eyes), varicella zoster virus group (2 patients, 2 eyes), and nonviral group (12 patients, 13 eyes) on the basis of detection of viral DNA in aqueous humor. The interval between keratoplasty and the onset of inflammation, changes in intraocular pressure (IOP), and corneal manifestations of inflammation were retrospectively reviewed.Sixteen of the 29 eyes developed anterior chamber inflammation within 2 years after keratoplasty. IOP during active inflammation was significantly increased in the HSV and CMV groups compared with preinflammation values, and the increased IOP was significantly ameliorated in association with resolution of inflammation. Linear-type keratoprecipitates were frequently detected in the HSV (5 of 8 eyes), CMV (3 of 6 eyes), and nonviral (6 of 13 eyes) groups. Corneal edema was also commonly observed in the HSV (7 of 8 eyes) and nonviral (13 of 13 eyes) groups.Changes in IOP and corneal manifestations may provide a basis for differentiation of viral endotheliitis from allograft rejection and among viral pathogens in individuals with anterior chamber inflammation after keratoplasty, and they may thus allow initiation of appropriate treatment before viral DNA is identified.

Herpesvirus entry mediator (HVEM), a member of the TNFR superfamily, serves as a unique molecular switch to mediate both stimulatory and inhibitory cosignals, depending on its functions as a receptor or ligand interacting with multiple binding partners. In this study, we explored the cosignaling functions of HVEM in experimental autoimmune uveitis (EAU), a mouse model resembling human autoimmune uveitis conditions such as ocular sarcoidosis and Behcet disease. Our studies revealed that EAU severity significantly decreased in HVEM-knockout mice compared with wild-type mice, suggesting that stimulatory cosignals from the HVEM receptor are predominant in EAU. Further studies elucidated that the HVEM cosignal plays an important role in the induction of both Th1- and Th17-type pathogenic T cells in EAU, including differentiation of IL-17–producing αβ+γδ− conventional CD4+ T cells. Mice lacking lymphotoxin-like, inducible expression, competes with herpes simplex virus glycoprotein D for HVEM, a receptor expressed by T lymphocytes (LIGHT), B- and T-lymphocyte attenuator (BTLA) or both LIGHT and BTLA are also less susceptible to EAU, indicating that LIGHT–HVEM and BTLA–HVEM interactions, two major molecular pathways mediating HVEM functions, are both important in determining EAU pathogenesis. Finally, blocking HVEM cosignals by antagonistic anti-HVEM Abs ameliorated EAU. Taken together, our studies revealed a novel function of the HVEM cosignaling molecule and its ligands in EAU pathogenesis through the induction of Th1- and Th17-type T cell responses and suggested that HVEM-related molecular pathways can be therapeutic targets in autoimmune uveitis.

Intervention studies have shown that n-3 polyunsaturated fatty acid (PUFA) supplementation is effective for the treatment of meibomian gland dysfunction (MGD). Ointment containing an analog of vitamin D has also been found to improve symptoms and signs of MGD. We have now evaluated the relation of MGD prevalence to dietary intake of fatty acids (FAs) and vitamin D among a Japanese population. Subjects comprised 300 adults aged 20 to 92 years residing on Takushima Island. MGD was diagnosed on the basis of subjective symptoms, lid margin abnormalities, and meibomian gland obstruction. Dietary FA and vitamin D intake was estimated with a brief-type self-administered diet history questionnaire. MGD prevalence was 35.3%. Multivariate adjusted odds ratios (95% confidence intervals) between extreme quintiles of intake for MGD prevalence were 0.40 (0.16&ndash, 0.97) for total fat, 0.40 (0.17&ndash, 0.97) for saturated FAs, 0.40 (0.17&ndash, 0.97) for oleic acid, 0.52 (0.23&ndash, 1.18) for n-3 PUFAs, 0.63 (0.27&ndash, 1.49) for n-6 PUFAs, 1.32 (0.59&ndash, 2.95) for the n-6/n-3 PUFA ratio, and 0.38 (0.17&ndash, 0.87) for vitamin D. Total fat, saturated FA, oleic acid, and vitamin D intake may thus be negatively associated with MGD prevalence in the Japanese.

To evaluate the efficacy and safety of intense pulsed light (IPL) combined with meibomian gland expression (MGX) for treatment of refractory meibomian gland dysfunction (MGD).Ninety eyes of 45 patients were randomly assigned to receive either the combination of IPL and MGX or MGX alone (control). Each eye underwent eight treatment sessions at 3-week intervals. Parameters were evaluated before and during treatment as well as at 3-11 weeks after the last treatment session. Measured parameters included the Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire score, noninvasive breakup time (NIBUT), fluorescein breakup time (BUT), lipid layer grade, lipid layer thickness (LLT), lid margin abnormalities, corneal and conjunctival fluorescein staining (CFS) score, meibum grade, and meiboscore.A significant improvement in lipid layer grade was apparent in the IPL-MGX group from 6 to 32 weeks after treatment onset (adjusted P 0.001) but was not observed in the control group. The IPL-MGX group also showed significant improvements in LLT, NIBUT, BUT, lid margin abnormalities, and meibum grade compared with the control group at 24 and 32 weeks (adjusted P 0.001) as well as significant improvements in the SPEED score at 32 weeks (adjusted P = 0.044) and in CFS score at 24 (adjusted P = 0.015) and 32 (adjusted P = 0.006) weeks.The combination of IPL and MGX improved homeostasis of the tear film and ameliorated ocular symptoms in patients with refractory MGD and is thus a promising modality for treatment of this condition.

The cornea focuses external light onto the retina, a function for which it must be transparent and possess a smooth surface. Homeostasis of the corneal epithelium is regulated by various humoral factors present in the tear fluid and by neural factors derived from the trigeminal nerve. Neurotrophic keratopathy (NK) is characterized by corneal epithelial disorders that result from impairment of trigeminal nerve function and a consequent deficiency of neural factors. The ideal mode of treatment for this condition is the regeneration of damaged trigeminal nerve fibers, but such therapy is not currently available. In this review, we describe established and potential new treatments of NK. Our research demonstrated that a combination of the neurotransmitter substance P and insulin-like growth factor 1 (IGF-1) has a synergistic stimulatory effect on corneal epithelial migration in vitro and on corneal wound closure in vivo. Furthermore, we identified the minimal amino acid sequences of substance P and IGF-1 required for this synergistic action based on the assumption that the clinical application of peptides corresponding to these sequences would have fewer side effects compared with the full-length molecules. Combination of the substance P-derived peptide FGLM-amide and the IGF-1-derived peptide SSSR promoted corneal epithelial wound healing in patients with NK.Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01756456.

Purpose To evaluate the effects of commercially available eyelid warming devices on ocular temperatures, tear film function, and meibomian glands in normal subjects and patients with meibomian gland dysfunction (MGD). Methods Ten healthy volunteers were enrolled to evaluate the effects of a single warming and of repeated warming for 2 weeks. Ten MGD patients were enrolled for evaluation of repeated warming over 1 month. Two non-wet (Azuki no Chikara, Eye Hot R) and three wet (hot towel, Hot Eye Mask, Memoto Este) devices were compared in a masked manner. Visual analog scale (VAS) score for ocular symptoms, tear film breakup time (TFBUT), meibum grade, temperatures (eyelid skin, tarsal conjunctiva, central cornea), Schirmer test value, and meibomian gland area were measured before and after warming application. Results The single application of the five warming devices improved the VAS score, TFBUT, and ocular temperatures. In the repeated warming application, Azuki no Chikara as a representative non-wet warming device induced a stable and significant improvement in TFBUT and increased the tarsal conjunctival temperature and meibomian gland area in both normal subjects and MGD patients. It also improved meibum grade in MGD patients. Conclusion Our results suggest that repeated eyelid warming with a non-wet device improves tear film function in normal individuals and may have beneficial effects on both tear film and meibomian gland function in MGD patients.

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–Sjogren 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 P P P = 0.0061, and P P = 8.3×10 −6 ). Conclusions An increase in tear fluid production likely compensates for loss of meibomian glands in individuals with MGD.

Meibomian glands secrete the oily layer of the tear film, which prevents excessive evaporation of tear fluid. Dysfunction of meibomian glands is not only one of the causes of evaporative dry eye but also one of the main causes of entire dry eye. To understand the pathophysiology of meibomian gland dysfunction, it is important to evaluate both the morphology and function of the meibomian gland. We previously reported that meibography enabled visualization of the morphology of the meibomian gland. Meanwhile, tear interferometry was introduced as an evaluation method for the function of the meibomian gland. We combined observations of the oily layer and the aqueous layer of the tear film and found that a tear film compensatory system may work toward maintenance of tear film homeostasis. In this review, we describe both morphological evaluation systems for the meibomian gland, including noninvasive meibography, and functional evaluation systems, including tear interferometry. We further describe the morphological changes of the meibomian glands in various ocular surface diseases. Finally, we demonstrate the concept of a tear film compensatory system and propose a method for tear film component-oriented diagnosis.

Numerous fixative solutions are available but many are not amenable to the histomorphological preservation of retinae. The investigators specifically focused on retinal histological studies, which rather than 4% formaldehyde (FA), often use Davidson’s fixative. However the latter has its limitations. The purpose of this study was to produce a new fixative which maintains retinae closer to the in vivo conditions. Experimental design. Four fixative formulations (4% paraformaldehyde, Davidson’s fixative, modified Davidson’s fixative and an in-house fixative – TB-Fix) were tested on retinae and the outcomes on histomorphology and immunohistochemical staining for selected antigenic markers was compared. TB-Fix markedly improved morphological detail following hematoxylin and eosin staining, most importantly eliminating the spongiform appearance in the plexiform layer and the swelling of somata (including Muller cells), when compared to FA, Davidson’s fixative and its modified version. Retinal samples fixed with TB-Fix or FA showed comparable results in immunohistological staining for neurons and glia in the retina. Importantly, while the whole eye fixed with FA collapsed in shape and induced artificial retinal detachment, the eye fixed with TB-Fix avoided deformation and detachment. Furthermore, we found that TB-Fix also prevented detachment from the culture plate when used to fix HEK293 cells, which are known to detach from the plate easily. It was demonstrated that TB-Fix provides an overall improvement in the preservation of retinal morphology and chemical composition.

PURPOSE Topical application of the fibronectin-derived peptide PHSRN facilitates corneal epithelial wound healing in healthy animals and in patients with nonhealing epithelial defects. We have now examined the effect of PHSRN eye drops on the healing of corneal epithelial wounds in diabetic rats. METHODS Wistar rats were injected intraperitoneally with streptozotocin to induce diabetes or with a vehicle as a control. Four weeks after confirmation of the corresponding presence or absence of glycosuria, a 3-mm-diameter portion of the corneal epithelium of the right eye was excised and eye drops containing PHSRN (200 μM) or phosphate-buffered saline (PBS) vehicle were administered to the injured eye every 6 hours. RESULTS The area of the epithelial defect did not differ significantly among the 4 experimental groups (diabetic or nondiabetic rats treated with PHSRN or vehicle) at 12 hours after wounding. At 18 hours, however, the area of the defect in diabetic rats treated with PHSRN (0.50 ± 0.34 mm) was significantly (P < 0.05) smaller than that in diabetic rats treated with PBS (1.06 ± 0.42 mm) and was similar to that in nondiabetic rats treated with PBS (0.60 ± 0.23 mm). The decrease in the size of the epithelial defect in diabetic rats treated with PHSRN was also found to be dependent on the dose of the peptide. CONCLUSIONS Administration of PHSRN significantly facilitated healing of corneal epithelial wounds in diabetic rats, which suggests that PHSRN eye drops warrant further investigation as a treatment option for patients with diabetic keratopathy.

Shima Fukuoka,1–3 Reiko Arita,2–4 Rika Shirakawa,2,3 Naoyuki Morishige2,5 1Department of Ophthalmology, Omiya Hamada Eye Clinic, 2Lid and Meibomian Gland Working Group (LIME), Saitama-shi, Saitama, 3Department of Ophthalmology, University of Tokyo School of Medicine, Bunkyo-ku, Tokyo, 4Department of Ophthalmology, Itoh Clinic, Saitama-shi, Saitama, 5Department of Ophthalmology, Oshima Eye Hospital, Fukuoka-shi, Fukuoka, Japan Purpose: To examine the changes in meibomian gland morphology and ocular higher-order aberrations (HOAs) in eyes with chalazion and its excision. Methods: Seven male patients with previous history of chalazion excision and seven control male subjects were enrolled. Changes in meibomian gland morphology (meiboscores, gland dropout, and shortening) were evaluated by using meibography equipped in a wavefront analyzer KR-1W and in a slit-lamp device BG-4M. Ocular HOAs were measured sequentially with KR-1W. The tear film breakup time (BUT) was measured. Results: Both KR-1W and BG-4M visualized meibomian gland as clear similar images. The tear film BUT (mean ± SD, 5.6±3.0 vs 9.4±2.3 seconds, P=0.025), the total meiboscore (median [interquartile range], 2 (2-3) vs 0 (0-1), P=0.007) as well as the meibomian gland dropout rate (86% vs 14%, P=0.008) and shortening rate (100% vs 29%, P=0.031) differed significantly between the patient and control groups. The first total ocular HOAs (0.142±0.063 vs 0.130±0.015, P=0.80) were similar in both groups, whereas the stability index of the total HOAs over time (0.0041±0.0048 vs -0.0012±0.0020, P=0.030) differed significantly between the patient and control groups. Conclusions: Chalazion and its excision were associated with dropout and shortening rate of meibomian glands. The morphological changes of meibomian glands in chalazion may be associated to instability of the tear film, which was suggested by the tear film BUT and the stability of ocular HOAs. Keywords: meibomian gland, meibography, wavefront analyzer, higher-order aberrations, chalazion excision

Menthol is thought to stimulate lacrimation via activation of cold-sensitive primary afferent neurons in the cornea. We evaluated a warm compress containing menthol as a potential treatment for dry eye by examining its effects on the tear film in healthy subjects (n = 20) and dry eye patients (n = 35). Disposable eyelid-warming steamers that either did (MH) or did not (HO) contain menthol were applied to one eye of each subject either once only for 10 min or repeatedly over 2 weeks. Single application of MH significantly increased tear meniscus volume (P = 8.6 × 10−5, P = 1.3 × 10−5) and tear film breakup time (P = 0.006, P = 0.002) as well as improved meibum condition in healthy subjects and dry eye patients, respectively. Repeated application of MH significantly increased tear meniscus volume (P = 0.004, P = 1.7 × 10−4) and tear film breakup time (P = 0.037, P = 0.010) in healthy subjects and dry eye patients, respectively. Repeated application of MH thus induced persistent increases in tear fluid volume and tear film stability in dry eye patients, suggesting that repeated use of a warm compress containing menthol is a potential novel treatment for dry eye disease.

Purpose To characterize the structural properties of collagen lamellae in the normal and keratoconic human corneal stroma, we measured their width and angle relative to Bowman's layer (BL). Methods Thirteen normal and four keratoconic corneas were examined. Collagen lamellae in tissue blocks from the central cornea were visualized by second harmonic generation imaging microscopy. Images obtained in 1-μm steps from BL to Descemet's membrane (DM) were subjected to three-dimensional reconstruction. The reconstructed data sets were divided into 10 layers of equal depth (L1-L10) for analysis. The width of lamellae adherent to BL (L0) was also determined. Results For the normal cornea, the width (mean ± SD) of collagen lamellae was 6.5 ± 1.7 μm at L0, decreased to 4.3 ± 1.3 μm at L1, and then increased gradually with progression toward DM to 122.2 ± 34.5 μm at L10, whereas the angle of lamellae was 20.9° ± 5.4° at L1 and decreased initially to 10.6° ± 3.2° at L2 before declining gradually to 2.7° ± 2.2° at L10. The width and angle of collagen lamellae in the keratoconic cornea were significantly larger and smaller, respectively, relative to those in the normal cornea. Conclusions In the normal human cornea, collagen lamellae adjacent to BL are narrow and form a steep angle with BL, whereas they increase in width and their angle relative to BL flattens with progression toward DM. These properties of collagen lamellae are altered in keratoconus and are likely related to abnormalities of corneal shape.

Purpose: To report a case of hypoplastic trigeminal nerve associated with corneal epithelial disorders that were successfully treated with peptides derived from substance P and insulin-like growth factor-1 (IGF-1). Case Report: A 16-month-old boy was referred for treatment of a persistent corneal epithelial defect on his left eye. Magnetic resonance imaging revealed the apparent absence of the trigeminal nerve on the left side, and the patient was therefore diagnosed with neurotrophic keratopathy. Treatment with eye drops containing the tetrapeptides FGLM-NH2 and SSSR derived from the neuropeptide substance P and the growth factor IGF-1, respectively, resulted in resurfacing of the corneal epithelial defect. Discussion: The trigeminal nerve anomaly of the patient likely gave rise to neurotrophic keratopathy as a result of a deficiency of neural factors, emphasizing the importance of neural regulation in corneal epithelial homeostasis.

Bullous keratopathy is categorized as a corneal endothelial disease. However, pathological changes, including subepithelial fibrosis and the accumulation of extracellular matrix, have been detected in the corneal stroma of individuals with this condition. In vivo confocal microscopy allows the visualization of human corneal cellular structures and has provided information regarding how eyes are affected by various diseases. However, the determination of disease pathogenesis on the basis of in vivo confocal microscopic observations is problematic. We evaluated the structural alterations in the corneal stroma of eyes affected by bullous keratopathy using second harmonic generation microscopy and laser confocal immunofluorescence microscopy of whole-mount preparations. Using these approaches, we detected the transdifferentiation of keratocytes into fibroblasts and myofibroblasts at the anterior and posterior stroma and the presence of subepithelial fibrosis at the anterior stroma and disorganized collagen lamellae at the posterior stroma of the bullous keratopathy cornea. These changes were only detected in specimens from eyes with stromal edema lasting at least 12 months. Similar time-dependent changes were apparent by using in vivo confocal microscopy in the corneal stroma of patients with bullous keratopathy after performing a Descemet stripping automated endothelial keratoplasty surgery and were associated with an unfavorable outcome with regard to postoperative visual acuity. Our observations suggest that pathological changes in the corneal stroma of patients with bullous keratopathy are progressive and affect postoperative visual acuity after a Descemet stripping automated endothelial keratoplasty surgery is performed.

We reported that the application of infrared camera enables us to observe iris morphology in Peters' anomaly through edematous corneas.To observe the iris morphology in bullous keratopathy or failure grafts with an infrared camera.Eleven bullous keratopathy or failure grafts subjects (6 men and 5 women, mean age ± SD; 72.7 ± 13.0 years old) were enrolled in this study. The iris morphology was observed by applying visible light mode and near infrared light mode of infrared camera (MeibomPen). The detectability of pupil shapes, iris patterns and presence of iridectomy was evaluated.Infrared mode observation enabled us to detect the pupil shapes in 11 out of 11 cases, iris patterns in 3 out of 11 cases, and presence of iridetomy in 9 out of 11 cases although visible light mode observation could not detect any iris morphological changes.Applying infrared optics was valuable for observation of the iris morphology through stromal edematous corneas.

Purpose To clarify the relationship between visual acuity after Descemet-stripping automated endothelial keratoplasty (DSAEK) and the preoperative duration of stromal edema. Setting Yamaguchi University Hospital, Yamaguchi, Japan. Design Comparative case series. Methods Patients who had DSAEK were divided into 2 groups based on whether the preoperative duration of stromal edema was less than 12 months (Group A) or more than 12 months (Group B). No patient had postoperative conditions that might have affected postoperative visual outcomes. Postoperatively, the corrected distance visual acuity (CDVA) was measured and the morphology of the anterior cornea evaluated by in vivo laser confocal microscopy. Results The postoperative CDVA in Group A ranged from 20/50 to 20/16 at 3 months and from 20/66 to 20/16 at 6 months; the maximum CDVA was 20/40 to 20/13. The postoperative CDVA in Group B ranged from 20/66 to 20/40 at 3 months and 6 months; the maximum CDVA was 20/66 to 20/33. The structure of the anterior cornea was normal in patients in Group A but was abnormal with fibroblastic cells in the anterior stroma in patients in Group B. Conclusions Patients with a preoperative duration of stromal edema of more than 12 months had pathologic changes in the corneal stroma that may have adversely affected visual acuity after DSAEK. Given that stromal edema, including that associated with bullous keratopathy, has been proposed to be a progressive condition, DSAEK may be most effective when performed early after the onset of edema, before the occurrence of pathologic changes in the stroma. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.

The R124C mutation of the TGFBI gene gives rise to lattice corneal dystrophy type I, which is characterized by irregularity, turbulence, and opacity of the corneal epithelium. We investigated the efficacy of corneal epithelial debridement followed by application of autologous fibronectin eye drops in the treatment of patients with this mutation. Four patients (6 eyes; age range 25–57 years) treated between April 2006 and March 2008 were enrolled in the study. All patients had impaired visual acuity and recurrent corneal erosion. Corneal epithelial debridement was performed with a spatula at the pupillary zone, after which eye drops containing fibronectin purified from autologous serum were administered four times daily for 2 weeks to promote epithelial migration. Topical levofloxacin and betamethasone were also applied four times daily for 1 month. All corneas achieved resurfacing within a few days of debridement. The best corrected visual acuity of all eyes improved from an average logMAR of 0.80 (range 1.40 logMAR–0.52 logMAR) before treatment to a logMAR of 0.10 (range 0.30 logMAR–0.046 logMAR) by 2–4 months after debridement. Despite the limitation of this study setting, corneal epithelial debridement followed by administration of fibronectin eye drops seems to be effective in improving visual acuity in cases of lattice corneal dystrophy type I caused by the R124C mutation of the TGFBI gene. This treatment may be one option for temporarily improving visual acuity in lattice corneal dystrophy type I and thus may delay the requirement for phototherapeutic keratoplasty or keratoplasty.

To detect the transdifferentiation of keratocytes into myofibroblasts in human corneas with bullous keratopathy and to examine the relation of such transdifferentiation to the clinical course of the disease.Twenty patients with bullous keratopathy who underwent penetrating keratoplasty were enrolled in the study. Corneal buttons collected during surgery were examined for expression of α-smooth muscle actin (αSMA) by immunoblot analysis and by immunofluorescence analysis of whole-mount preparations. The course of bullous keratopathy was evaluated from clinical charts.Immunoblot analysis revealed a marked increase in αSMA expression in some corneas affected by bullous keratopathy. Immunofluorescence analysis revealed that αSMA was expressed in myofibroblastic cells in the stroma of 10 of the 20 corneas examined. Expression of αSMA was detected in subjects with a clinical history of corneal epithelial erosion from 12 months after the onset of clinical stromal edema. In contrast, in subjects without a clinical history of epithelial erosion, αSMA expression was not detected until at least 27 months after the onset of stromal edema. The incidence of αSMA expression in stromal cells was not significantly associated with topical steroid administration.Transdifferentiation of keratocytes into myofibroblasts was observed in human corneas affected by bullous keratopathy. Such transdifferentiation occurred earlier after the onset of stromal edema in patients with a clinical history of epithelial erosion than in those without such a history.

Infected cell protein 0 (ICP0) has been detected in the tear fluid of rabbits with herpetic keratitis. Here, we investigated whether ICP0 of herpes simplex virus 1 is detectable in the tear fluid of patients with herpetic epithelial keratitis.Seven patients with herpetic epithelial keratitis (age range, 51-76 years) and 11 healthy volunteers (age range, 48-85 years) were enrolled in the study. Tear fluid was collected with the use of Schirmer test strips and subjected to immunoblot analysis with antibodies to ICP0.ICP0 was not detected in the tear fluid of the healthy controls, whereas it was detected in 4 of the 7 patients with herpetic keratitis. The tear fluid of the 4 ICP0-positive patients was collected within 3 days of the onset of keratitis, whereas that of the ICP0-negative patients was obtained at least 7 days after disease onset.ICP0 was detected in the tear fluid of patients in the early phase of herpetic epithelial keratitis, but not in that of patients in the later stages of the disease nor in that of the healthy controls. ICP0 expression may thus be dependent on the disease phase.

Background: To develop a novel quantitative index for evaluation of corneal epithelial oedema, the pixel intensity of confocal microscopic images was measured derived from the basal cell layer (BCL) of the corneal epithelium in normal eyes, eyes before and after cataract surgery, and eyes affected by bullous keratopathy. Methods: Five eyes of five normal volunteers, 14 eyes of 11 cataract patients and 12 eyes of 12 bullous keratopathy patients were examined by confocal microscopy. The cataract patients underwent cataract surgery, and they were examined by confocal microscopy, corneal pachymetry, and anterior fluorometry both before and at various times after surgery. The pixel intensity of BCL images obtained by confocal microscopy was measured and expressed as the BCL index. Results: The coefficient of variation for repeated (five times) measurement of the BCL index in each of the five normal eyes was 3.4%. The BCL index was 54.8 ± 5.3 (mean ± SD) before surgery, increased significantly to 65.2 ± 10.0 on the day after surgery, and gradually decreased thereafter in the cataract patients. The time-course of the BCL index coincided well with that of corneal thickness and anterior fluorometry value. The BCL index in eyes affected by bullous keratopathy was significantly increased at 95.0 ± 6.4. Conclusion: The BCL index was increased after cataract surgery and in eyes affected by bullous keratopathy, conditions associated with corneal epithelial oedema. This quantitative measure obtained by confocal microscopy may prove useful in the clinical evaluation of corneal epithelial oedema.

Semaphorins are a family of glycoproteins that play an important role in repulsive axon guidance during embryogenesis. We have now investigated the effect of corneal epithelial cells on the expression of Sema3A in corneal fibroblasts with the use of a coculture system in which the two cell types are separated by a collagen vitrigel membrane. Reverse transcription-polymerase chain reaction and immunoblot analyses revealed that the presence of immortalized human corneal epithelial (HCE) cells increased the expression of Sema3A in human corneal fibroblasts at both the mRNA and protein levels. This effect of HCE cells was mimicked by recombinant human epidermal growth factor (EGF) in a concentration- and time-dependent manner. An inhibitor of the tyrosine kinase activity of the EGF receptor, PD153035, blocked the EGF-induced up-regulation of both Sema3A mRNA and protein in corneal fibroblasts. Depletion of EGF in HCE cells by RNA interference largely abolished the effect of these cells on Sema3A expression in corneal fibroblasts. These findings indicate that EGF released from corneal epithelial cells up-regulates the expression of Sema3A in corneal fibroblasts. This effect of EGF may play an important role in maintenance of corneal structure and repair of corneal damage.

Author(s): Jester, JV; Morishige, N; BenMohamed, L; Brown, DJ; Osorio, N; Hsiang, C; Perng, GC; Jones, C; Wechsler, SL | Abstract: Purpose: Using CJLAT, a chimeric herpes simplex virus (HSV-1) that produces a high incidence of herpes stromal keratitis (HSK) in latently infected rabbits, and in vivo confocal microscopy (CM), we characterized the cellular events that precede the development of HSK. Methods: Thirty days after infection, in vivo CM was performed daily for 10 days and then weekly for up to 80 days after infection. Results: We detected 3 types of subclinical corneal lesions before HSK was clinically apparent: (1) small epithelial erosions; (2) regenerating epithelium overlying small cell infiltrates within the basal epithelial cell layer; and (3) dendritic-like cells within the basal epithelial layer overlying stromal foci containing infiltrating cells. Sequential in vivo CM observations suggested that subclinical foci resolved over time but were larger and more abundant with CJLAT than with wild-type HSV-1 McKrae. Active HSK was observed only with CJLAT and was initially associated with a large epithelial lesion overlying stromal immune cell infiltrates. Conclusions: These results suggest that replication in the cornea of reactivated virus from the trigeminal ganglia produces epithelial lesions, which recruit immune cell infiltrates into the basal epithelial layer and anterior stroma. The virus is usually cleared rapidly eliminating viral antigens before the arrival of the immune cells, which disperse. However, if the virus is not cleared rapidly, or if an additional reactivation results in an additional round of virus at the same site before the immune cells disperse, then the immune cells are stimulated and may induce an immunopathological response leading to the development of HSK.

The loss of corneal sensation results in the development of persistent corneal epithelial defects. The combination of a substance P-derived peptide, phenylalanine -glycine-leucine-methionine (FGLM)-amide, and insulin-like growth factor 1 (IGF-1) stimulates corneal epithelial migration in vitro and corneal epithelial wound closure in vivo. The clinical efficacy of eye drops containing FGLM-amide and IGF-1 for the treatment of persistent epithelial defects in individuals with neurotrophic keratopathy was examined in a prospective open study. Eleven patients with persistent corneal epithelial defects associated with neurotrophic keratopathy were treated for up to 28 days by the administration of eye drops containing FGLM-amide and IGF-1. The course of epithelial healing was monitored by slit-lamp examination, and visual acuity was measured before and after treatment. Complete epithelial resurfacing was achieved in eight of the nine (89%) cases of persistent epithelial defects in the nine patients who received the full course of treatment. Epithelial defects had completely resurfaced in two of nine (22%) and five of nine (56%) cases within 1 and 2 weeks, respectively, after treatment initiation. No adverse effects of treatment were observed in any of the 11 patients. Eye drops containing FGLM-amide and IGF-1 induced the rapid resurfacing of persistent epithelial defects in individuals with neurotrophic keratopathy. Jpn J Ophthalmol 2007;51:442–447 © Japanese Ophthalmological Society 2007

We studied the phenotype and distribution of “naturally” occurring CD4+CD25+T regulatory cells (CD4+CD25+nTregcells) resident in rabbit conjunctiva, the main T-cell inductive site of the ocular mucosal immune system, and we investigated their suppressive capacities using herpes simplex virus type 1 (HSV-1)-specific effector T (Teff) cells induced during ocular infection. The expression of CD4, CD25, CTLA4, GITR, and Foxp3 was examined by reverse transcription-PCR, Western blotting, and fluorescence-activated cell sorter analysis in CD45+pan-leukocytes isolated from conjunctiva, spleen, and peripheral blood monocyte cells (PBMC) of HSV-1-infected and uninfected rabbits. Normal conjunctiva showed a higher frequency of CD4+CD25(Bright+)T cells than did spleen and PBMC. These cells expressed high levels of Foxp3, GITR, and CTLA4 molecules. CD4+CD25(Bright+)T cells were localized continuously along the upper and lower palpebral and bulbar conjunctiva, throughout the epithelium and substantia propria. Conjunctiva-derived CD4+CD25(Bright+)T cells, but not CD4+CD25(low)T cells, efficiently suppressed HSV-specific CD4+and CD8+Teffcells. The CD4+CD25(Bright+)T-cell-mediated suppression was effective on both peripheral blood and conjunctiva infiltrating Teffcells and was cell-cell contact dependent but independent of interleukin-10 and transforming growth factor β. Interestingly, during an ocular herpes infection, there was a selective increase in the frequency and suppressive capacity of Foxp3+CD4+CD25(Bright+)T cells in conjunctiva but not in the spleen or in peripheral blood. Altogether, these results provide the first evidence that functional Foxp3+CD4+CD25(Bright+)Tregcells accumulate in the conjunctiva. It remains to be determined whether conjunctiva CD4+CD25+nTregcells affect the topical/mucosal delivery of subunit vaccines that stimulate the ocular mucosal immune system.

Diabetic complications are associated with abnormality of the basement membranes. We have developed a light-scattering detection system (LSDS) specifically for measurement of light scattering at the corneal epithelial basement membrane, and have determined the reproducibility and clinical significance of the results obtained by the LSDS in diabetic patients.Thirty nondiabetic controls and 40 diabetic subjects participated in the study. Light scattering at the corneal epithelial basement membrane was measured with the LSDS.The measurement of light scattering at the corneal basement membrane was found to be reproducible. The LSDS index (mean +/- SD) was 28.1 +/- 4.8 in controls, 35.7 +/- 6.3 in mild diabetic retinopathy subjects, and 42.7 +/- 8.6 in severe diabetic retinopathy subjects. This demonstrated that the LSDS index at the corneal basement membrane is proportional to the extent of diabetic retinopathy.Measurement of light scattering at the corneal epithelial basement membrane is possible with the LSDS, is relatively easy to perform, and is reproducible. The LSDS may prove suitable for the early detection of diabetic ocular complications.