Effect of Artificial Tears on Preoperative Keratometry and Refractive Precision in Cataract Surgery.

Purpose: The primary objective was to investigate if treatment with artificial tears affected the variability of keratometry measurements for subjects with dry eyes prior to cataract surgery. The secondary objectives were to investigate whether treatment with artificial tears improved refractive precision and whether subjects with non-dry eyes had better refractive precision than subjects with dry eyes. Design: Prospective randomized controlled trial with three arms. Patients and methods: Dry eye diagnostics according to DEWS II were performed, and subjects with dry eyes were randomized to no treatment (group A1) or treatment with artificial tears two weeks prior to cataract surgery (group A2), with the third group (Group B, non-dry eyes) as a control. Keratometry was performed twice at baseline and twice after two weeks at the time of cataract surgery with three different optical biometers. The change in mean variability of keratometry (average K and magnitude of vector differences) and percentages of outliers after two weeks versus baseline were compared for group A2. The refractive and astigmatism prediction errors were calculated eight weeks after cataract surgery and compared for all three groups. Results: One hundred thirty-one subjects were available for analysis. There was no statistically significant difference in the mean variability of keratometry or percentages of outliers for group A2 from baseline to the time of cataract surgery. There was no statistically significant difference in refractive precision (absolute error and astigmatism prediction error) between any groups. Conclusion: Subjects with dry eyes (treated and non-treated) achieved the same refractive precision and percentages of outliers as subjects with non-dry eyes. Treatment with artificial tears for two weeks appeared inadequate to significantly affect variability in biometric measurements for patients with dry eyes prior to cataract surgery. DEWS II criteria for DED may not be optimal in a cataract setting.

Method Development for Omics Analyses using Schirmer Strips.

PURPOSE: The aim of this article was to investigate whether Schirmer strips gathered during clinical dry eye examinations can be prepared for omics analyses in a standardized way, to adjust for variations in tear volume and enable two separate omics analyses from the same sample. In addition, the intention was to investigate whether fluorescein dye instillation in the eyes gave bias effects on metabolomic analysis. METHODS: Twelve samples from six individuals, with normal or reduced tear production, were collected. Half of the samples were harvested after instillation of fluorescein in the eye. Each strip was divided in half along the length and prepared with a new method for extracting tear content from the Schirmer strip. The new method was established to compensate for different dilutions of metabolites in varying Schirmer strip wetting levels when using identical extraction volume for all samples. Metabolomic data were compared in samples with and without fluorescein dye and Schirmer strips ranging from 1 to 35 mm wetting levels using a global LC-MS method. RESULTS: All samples were successfully analyzed with an average of ∼350 relevant features detected per sample after using both positive and negative electrospray ionization mode, despite low tear volumes in some samples and that only one half of the Schirmer strips were used. Principal component analysis plots and heatmaps revealed no bias effects of fluorescein dye presence or different Schirmer strip values when using the proposed method. CONCLUSION: A high number of relevant metabolomic features can be extracted from longitudinally cut halves of Schirmer strips, which may enable analyses with more than one omics modality from the same sample. With the pre-analytical method described, Schirmer strips can be used for metabolomic analyses even in cases of very low or high tear volume with or without fluorescence.

A Preservative-Free Approach - Effects on Dry Eye Signs and Symptoms After Cataract Surgery.

Purpose: To compare the effect of treatment with preservative-free dexamethasone, NSAIDs and trehalose/hyaluronic acid eye drops with the preservative benzalkonium chloride containing dexamethasone and NSAIDs after cataract surgery in dry versus non-dry eyes. Patients and Methods: In this prospective randomized intervention study, dry eye tests were performed before and 6 weeks after cataract surgery. Patients were considered as having dry eye, SDE (sign of dry eye), if at least one of the following dry eye tests were abnormal; corneal fluorescein staining (CFS), non-invasive keratograph breakup time (NIKBUT) or tear osmolarity. Patients with SDE were randomly assigned to one of two groups. Group 1 patients were treated with dexamethasone and bromfenac eye drops with the preservative benzalkonium chloride (BAC). Group 2 patients were treated with preservative-free dexamethasone and preservative-free diclofenac, as well as a preservative-free lubricant with trehalose and hyaluronic acid both before and after surgery. Patients with normal tear film status acted as the control group (group 3) and received same treatment as group 1. Results: A total of 215 patients were enrolled six weeks after surgery, the number of patients with SDE decreased significantly in groups 1 and 2 (p <0.001). Subjective symptoms and objective measures including osmolarity, NIKBUT, CFS, and tear film thickness (TFT) improved after surgery, tear production remained unchanged, while corneal sensitivity and meibomian gland dysfunction (MGD) parameters worsened. In the control group with normal tear-film status, SDE increased significantly after the surgery (p <0.001). There were no statistically significant differences in tear film parameters between the three groups after surgery. Conclusion: After cataract surgery, patients with mild to moderate dry eyes may experience improved tear film status and reduced symptoms. However, we found no additional beneficial effect on dry eye parameters with treatment with preservative-free dexamethasone, NSAIDs, and lubricants compared to preservative-containing eye drops.

The Significance of Dry Eye Signs on Preoperative Keratometry Measurements in Patients Scheduled for Cataract Surgery.

Purpose: The primary objective was to investigate if subjects with dry eyes had increased variability of keratometry measurements prior to cataract surgery compared to subjects with non-dry eyes. Secondary objectives were to determine which separate signs affected keratometry. Patients and Methods: This study was part of a prospective interventional randomized controlled trial. After dry eye diagnostics were performed (signs only) subjects were divided into sign of dry eye (SDE) positive and negative groups. To investigate variability, we performed two keratometry measurements for each subject with three different optical biometers: Anterion (OCT optical biometer), Eyestar (combined OCT and reflection-based optical biometer), and Lenstar (reflection based-optical biometer). Results: One hundred and thirty-one subjects were available for analysis. The variability of astigmatism was significantly higher for subjects with hyperosmolarity compared to normal eyes for the Lenstar, as was the percentage of eyes with variability of astigmatism greater than 0.25 D. The percentage of eyes with variability of average K greater than 0.25 D was higher for subjects with non-invasive keratograph break-up time <10 seconds (NIKBUT positive) compared to normal eyes for the Lenstar. Conclusion: Combined diagnostic criteria (signs only) showed no statistically significant differences for keratometry measurements between SDE positive and negative. Eyes with hyperosmolarity and NIKBUT positive showed statistically higher variability of keratometry measurements compared to normal eyes for Lenstar, but not for the Anterion or Eyestar biometers.

Prevalence of Dry Eye Disease Among Individuals Scheduled for Cataract Surgery in a Norwegian Cataract Clinic.

Purpose: To determine the prevalence of dry eye disease (DED) in patients scheduled for cataract surgery in a Norwegian eye clinic. Patients and Methods: 218 patients scheduled for cataract surgery were examined for DED in one randomly selected eye and questioned regarding symptoms and risk factors. Patients were diagnosed with DED if they fulfilled the DEWS II criteria with symptom score >12/100 with Ocular Surface Disease Index (OSDI) questionnaire, and the presence of any of the three signs: tear osmolarity >307 mOsm/L in either eye or a difference in osmolarity between the two eyes of >8 mOsm/L, corneal fluorescein staining (CSF) ≥ grade 2 and non-invasive tear film breakup time (NIKBUT) of <10 seconds. Additional tests were the Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire, tear meniscus height (TMH), Schirmer 1, tear film thickness (TFT), corneal sensitivity and meibography (meiboscore). Dry eye test outcomes were correlated with risk factors for DED. Results: The prevalence of DED was 55.5% according to the DEWS II criteria. The abnormal osmolarity percentage was 66.5, while 29.8% had shortened NIKBUT and 19.7% exhibited CFS ≥2. 57% had Schirmer 1 ≤ 10 mm/5 min, and 81.1% had a meiboscore of ≥1. 71.2% of subjects scored positive for DED symptoms using the OSDI questionnaire and 69.3% using SPEED. Logistic regression analysis showed that higher age correlated with a lower OSDI symptom score, reduced corneal sensitivity and increased meibomian gland atrophy. Female sex was associated with higher odds of having DED, abnormal NIKBUT and abnormal CFS. Ocular tests for DED did not correlate with OSDI symptom scores when assessed with Spearman`s rank analysis. Conclusion: The prevalence of DED in an elderly Norwegian population scheduled for cataract surgery is high and associated with female sex. There was a lack of correlation between signs and symptoms of DED.

Rod and Cone Dark Adaptation in Congenital Aniridia and Its Association With Retinal Structure.

Purpose: To characterize the association between dark-adapted rod and cone sensitivity and retinal structure in PAX6-related aniridia. Methods: Dark-adaptation curves were measured after a 5-minute exposure to bright light with red (625 nm) and green (527 nm) 2° circular light stimuli presented at ≈20° temporal retinal eccentricity in 27 participants with aniridia (nine males; 11-66 years old) and 38 age-matched healthy controls. A two-stage exponential model was fitted to each participant's responses to determine their cone and rod thresholds over time. The thicknesses of macular inner and outer retinal layers were obtained from optical coherence tomography images in 20 patients with aniridia and the 38 healthy controls. Aniridia-associated keratopathy (AAK) grade (0-3) and lens opacities were quantified by clinical examination of the anterior segment. Results: The rod-cone break time was similar between patients with aniridia and healthy controls. Dark-adapted cone and the rod thresholds were higher in aniridia compared with healthy controls. In aniridia, foveal outer retinal layer thickness correlated with both final cone and rod thresholds. A multiple regression model indicated that foveal outer retinal layer thickness and age were the main explanatory variables to predict both final cone and rod thresholds in aniridia when the AAK grade was 2 or less. Conclusions: The results show that both rod- and cone-related functions are affected in PAX6-related aniridia and suggest that retinal anatomical and physiological changes extend beyond the area commonly studied in this condition: the central macula.

The Significance of Inter-Eye Osmolarity Difference in Dry Eye Diagnostics.

Purpose: The purpose of this study was to evaluate the diagnostic value of inter-eye osmolarity differences in relation to dry eye symptoms and other non-osmolar signs of dry eye disease. Patients and Methods: One hundred ninety one participants who attended a larger interventional study of dry eye disease prior to and after cataract surgery were analyzed for dry eye disease (DED). Dry eye diagnostics were performed for all subjects according to the DEWS II criteria: tear osmolarity was collected from both eyes with the TearLab system, non-invasive Tear film break up time (NIKBUT) was obtained on the test eye with Keratograph and ocular surface staining (OSS) was evaluated using the Oxford schema. The Ocular Surface Disease Index (OSDI) questionnaire was used to assess symptoms. Inter-eye osmolarity greater than 8, which is considered as a sign of DED according to the TearLab user manual, was evaluated and compared with other non-osmolar signs of DED. Results: The 191 subjects were divided into three groups according to osmolarity measurements. Sixty-five subjects had normal osmolarity (below 308 mOsmol/L in both eyes and less than 9 mOsmol/L difference between the eyes), 107 had high osmolarity (308 mOsmol/L or higher in one of the eyes) and 19 had an inter-eye difference >8 mOsmol/L or higher, with neither eye having osmolarity higher than 307 mOsmol/L. Signs and symptoms in this last group were not correlated with the high osmolarity group or the normal group, though they appeared more similar to the normal group. Conclusion: The diagnostic value of inter-eye osmolarity difference in predicting symptoms or other non-osmolar signs of dry eyes appears weak. Our study suggests that the criterion of an inter-eye difference of 8 mOsmol/L is not a useful cut-off for diagnosing dry eyes based on osmolarity.

Meibomian gland dysfunction is highly prevalent among first-time visitors at a Norwegian dry eye specialist clinic.

To investigate the prevalence of meibomian gland dysfunction (MGD) in patients presenting with subjective dry eye-related symptoms at their first-time consultation in a Norwegian specialized ocular surface clinic. Additionally, to explore the accuracy of the ocular surface disease index score (OSDI) as an extensively applied tool to assess the severity of dry eye symptoms and MGD diagnosis. Patients with subjective dry eye-related complaints (n = 900) attending the clinic for the first time, from 2012 to 2016, were included in the study. At the baseline, patients completed the OSDI questionnaire. Subsequently, objective clinical tests, including fluorescein break-up time (FBUT), Schirmer-I test, ocular surface staining (OSS), and meibomian gland function assessment using gland expressibility and meibum quality were performed. The association between MGD and its severity in relation to symptom severity defined by OSDI-score was examined. MGD was found in 93.8% of the study group. MGD prevalence was not significantly different between groups based on age (p = 0.302) or sex (p = 0.079). There was a significant association between severity of MGD and dry eye-related symptoms (p = 0.014). OSS was significantly higher in patients with severe symptoms (p = 0.031). Sensitivity and specificity of positive symptom-score (OSDI ≥ 13) for disclosing MGD were 85.5% and 30.4%, respectively. MGD was highly prevalent, not associated with age and sex. OSDI ≥ 13 had high sensitivity and high positive predictive value (PPV), but low specificity and negative predictive value (NPV) for disclosing MGD. This underscores the importance of meibomian gland assessment in patients with dry eye-related symptoms.

TheraPearl Eye Mask and Blephasteam for the treatment of meibomian gland dysfunction: a randomized, comparative clinical trial.

Meibomian gland dysfunction (MGD) is the most common cause of dry eye disease (DED). In this study, we aimed to compare the effects of eyelid warming treatment using either TheraPearl Eye Mask (Bausch & Lomb Inc., New York, USA) or Blephasteam (Spectrum Thea Pharmaceuticals LTD, Macclesfield, UK) in a Norwegian population with mild to moderate MGD-related DED. An open label, randomized comparative trial with seventy patients (49 females, 21 males; mean age 53.6 years). Patients were randomly assigned to treatment with Blephasteam (n = 37) or TheraPearl (n = 33). All received a hyaluronic acid based artificial tear substitute (Hylo-Comod, Ursapharm, Saarbrücken, Germany). Patients were examined at baseline, and at three and six months initiation of treatment. Treatment efficacy was primarily evaluated by fluorescein breakup time (FBUT) and Ocular Surface Disease Index (OSDI) scores. Other outcome measures included ocular surface staining (OSS), Schirmer's test, and meibomian quality and expressibility. Baseline parameter values did not differ between the groups. After six months of treatment, Blephasteam improved FBUT by 3.9 s (p < 0.01) and OSDI by 13.7 (p < 0.01), TheraPearl improved FBUT by 2.6 s (p < 0.01) and OSDI by 12.6 (p < 0.01). No difference between treatments was detected at 6 months (p = 0.11 for FBUT and p = 0.71 for OSDI), nor were there differences in the other tested parameters between the treatment groups. Blephasteam and TheraPearl are equally effective in treating mild to moderate MGD in a Norwegian population after 6-months of treatment.Clinicaltrials.gov ID: NCT03318874; Protocol ID: 2014/1983; First registration: 24/10/2017.

Alterations in meibomian glands in patients treated with intensity-modulated radiotherapy for head and neck cancer.

Patients undergoing intensity-modulated radiotherapy (IMRT) for head and neck cancer may have increased incidence of dry eye disease and the exact mechanism is unclear. The present study aims to assess tear film and meibomian gland (MG) features in patients who received IMRT for head and neck cancer not involving the orbital area. Twenty-seven patients (64.7 ± 9.8 years) and 30 age-matched controls (61.4 ± 11.0 years) underwent a comprehensive dry eye work-up. Compared to the control group, the patients had more lid margin abnormalities, and worse meibum quality. The MG loss, calculated as (tarsal area-MG area)/tarsal area, was higher in the patient group in both the upper (53.0 ± 12.0% vs. 35.1 ± 10.3%, p < 0.001) and lower lids (69.5 ± 12.6% vs. 48.5 ± 12.5%, p < 0.001). In the patient group, more MG loss in the lower lids correlated with worse meibum quality (r = 0.445, p = 0.029). In contrast, there was no significant difference in aqueous tear production level, measured with Schirmer test. Patients treated with IMRT for head and neck cancer seemed to have comparable lacrimal gland function to the controls despite more dry eye symptoms. However, the patients had MG functional and morphological changes, which may present a higher risk for developing dry eye disease.

Tear Film Break-Up Time and Dry Eye Disease Severity in a Large Norwegian Cohort.

This study evaluated to what extent tear film break-up time (TFBUT) could discriminate pathological scores for other clinical tests and explore the associations between them. Dry eye patients (n = 2094) were examined for ocular surface disease index (OSDI), tear film osmolarity (Osm), TFBUT, blink interval, ocular protection index (OPI), ocular surface staining (OSS), Schirmer I test, meibomian expressibility, meibomian quality, and meibomian gland dysfunction. The results were grouped into eight levels of break-up time (≤2, ≥3, ≤5, ≥6, ≤10, ≥11, ≤15, and ≥16) with or without sex stratification. Receiver-operating characteristic curve (ROC) analysis and Pearson's correlation coefficients were used to study TFBUT's discriminative power and the associations among the tests, respectively. Above and below each TFBUT's cut-off, all of the parameters indicated significant difference between groups, except OSDI (cut-off 15 s) and Osm (cut-offs 5 s-15 s). At TFBUT cut-off of 2 s, sex difference could be detected for OSDI, Osm, and OSS. OPI presented the strongest discriminative power and association with TFBUT in sharp contrast to Osm, holding the poorest discriminative power with no significant correlation. The remaining parameters were within the poor to very poor categories, both with regard to discrimination and correlation. In conclusion, patients with lower TFBUT presented with more severe DED parameters at all four defined cut-off values.

Sex and age differences in symptoms and signs of dry eye disease in a Norwegian cohort of patients.

PURPOSE: To investigate sex and age differences in symptoms and signs in a Norwegian clinic-based cohort of patients with dry eye disease (DED). METHODS: Visitors at the Norwegian Dry Eye Clinic were examined using Ocular Surface Disease Index (OSDI) questionnaire score, tear osmolarity, tear break-up time (TFBUT), ocular surface staining, corneal sensitivity, Schirmer I test, and meibum expressibility (ME) and quality (MQ). A diagnosis of DED was made by an ophthalmologist based on symptoms and signs, and only DED patients were enrolled in the study: 1823 patients (338 males; mean age 51.2 ± 16.2 years; 1485 females; mean age 52.5 ± 16.0 years). The patients were divided into age subgroups: 20-39 years, 40-59 years and ≥60 years. Sex differences in the aforementioned tests were analyzed. Values were reported as mean ± standard deviation (SD), and intergroup comparisons were performed using Mann-Whitney U test. Multiple regression was used to analyze sex and age influences on symptoms and signs. RESULTS: When patients of all ages were analyzed, females had increased osmolarity, shorter TFBUT, reduced MQ and ME and higher corneal sensitivity. OSDI, Schirmer I test, ocular surface staining and corneal staining were not significantly different between the sexes. Only with TFBUT and ME were the sex difference present in all age subgroups. Multiple regression showed that all parameters were influenced by either sex or age, but only TFBUT and ME were influenced by both sex and age. (all p < 0.05). CONCLUSIONS: Sex and age differences in dry eye were most consistent in TFBUT and ME, that indicate differences in meibomian gland functionality. Sex and age subgroup stratification is important in future studies investigating DED in other populations.

PAX6 Genotypic and Retinal Phenotypic Characterization in Congenital Aniridia.

Purpose: To investigate the association between PAX6 genotype and macular morphology in congenital aniridia. Methods: The study included 37 participants (15 males) with congenital aniridia (aged 10-72 years) and 58 age-matched normal controls (18 males). DNA was isolated from saliva samples. PAX6 exons, intron/exon junctions, and known regulatory regions were amplified in PCR and sequenced. Multiplex ligation-dependent probe amplification (MLPA) was performed to detect larger deletions or duplications in PAX6 or known cis-regulatory regions. Spectral-domain optical coherence tomography images were acquired and segmented semiautomatically. Mean thicknesses were calculated for inner and outer retinal layers within the macula along nasal and temporal meridians. Results: Mutations in PAX6 or regulatory regions were found in 97% of the participants with aniridia. Foveal hypoplasia was observed in all who had a mutation within the PAX6 gene. Aniridic eyes had thinner outer retinal layers than controls, but with large between-individual variation (mean ± SD, 156.3 ± 32.3 µm vs 210.8 ± 12.3 µm, P < 0.001). Parafoveal and perifoveal inner and outer retinal layers were thinner in aniridia. Participants with mutations in noncoding PAX6 regions had thicker foveal outer retinal layers than those with mutations in the PAX6 coding regions (P = 0.04) and showed signs of postnatal development and maturation. Mutations outside the PAX6 gene were associated with the mildest retinal phenotypes. Conclusions: PAX6 mutations are associated with significant thinning of macular inner and outer retinal layers, consistent with misdirected retinal development resulting in abnormal foveal formation and reduced number of neurons in the macula, with mutations in PAX6 coding regions giving the worst outcome.

Utility of Tear Osmolarity Measurement in Diagnosis of Dry Eye Disease.

The prevalence of dry eye disease is high worldwide and poses a great burden on patients' daily lives. Accurate diagnosis of the disease is important, and it requires application of various methods. Hyperosmolarity is believed to be the disease marker and thus measuring it provides useful information. In this study we investigated utility of tear osmolarity measured with TearLab osmometer, along with other diagnostic tests (Ocular Surface Disease Index questionnaire, Tear film break-up time, Ocular Protection Index, Ocular Surface Staining, Schirmer I test, Meibomian gland functionality in 757 patients (1514 eyes) with dry eye disease and 29 healthy controls (58 eyes). Statistical differences between the patient group and the control group were observed for all the tests apart from tear osmolarity, regardless of cut-off value (>308 mOsm/L, >316 mOsm/L, and inter-eye difference >8 mOsm/L). Moreover, in the receiver operating characteristics curve analyses tear osmolarity measurement could not discriminate dry eye disease pathological scores. Therefore, our study suggests that tear osmolarity measured with TearLab osmometer cannot be used as a key indicator of DED.

Functional and Morphological Evaluation of Meibomian Glands in the Assessment of Meibomian Gland Dysfunction Subtype and Severity.

PURPOSE: To classify subtypes of meibomian gland dysfunction (MGD) and evaluate the dependency of dry eye signs, symptoms, and parameters on MGD subtype. DESIGN: Cross-sectional study. STUDY POPULATION: the right eyes of 447 patients with MGD of various subtypes and 20 healthy volunteers. METHODS: Patients were divided into 4 subtypes of MGD based on meibum expression, meibum quality, and MG loss on meibography images (meibograde of 0-6). Subtypes were patients with high meibum delivery (hypersecretory and nonobvious MGD) and those with low meibum delivery (hyposecretory and obstructive MGD). Additional clinical tests included tear film break-up time (TFBUT), ocular staining, osmolarity, Schirmer I, blink interval timing and the Ocular Surface Disease Index (OSDI) questionnaire. RESULTS: A total of 78 eyes had hypersecretory MGD; 49 eyes had nonobvious MGD; 66 eyes had hyposecretory MGD; and 254 eyes had obstructive MGD. Increased tear film osmolarity and lower TFBUT were found in the low-delivery groups; hyposecretory (P = 0.006, P = 0.016) and obstructive MGD (P = 0.008, P = 0.006) relative to high-delivery MGD (hypersecretory and nonobvious groups, respectively). Worse ocular symptoms and ocular staining were also found in low-delivery MGD groups than the high delivery MGD groups (P < 0.01 and P < 0.006, respectively). CONCLUSIONS: Patients with low-delivery MGD had worse dry eye parameters and ocular symptoms than those with high meibum delivery, indicating the pivotal role of meibum secretion in ocular surface health that should be targeted in MGD therapy. Furthermore, nonobvious MGD cannot be diagnosed using conventional dry eye tests and requires morphologic assessment of meibography images to confirm MG loss.

Diagnostic Test Efficacy of Meibomian Gland Morphology and Function.

Meibomian gland dysfunction (MGD) is the leading cause of dry eye and proposed treatments are based on disease severity. Our purpose was to establish reliable morphologic measurements of meibomian glands for evaluating MGD severity. This retrospective, cross-sectional study included 100 MGD patients and 20 controls. The patients were classified into dry eye severity level (DESL) 1-4 based on symptoms and clinical parameters including tear-film breakup time, ocular staining and Schirmer I. The gland loss, length, thickness, density and distortion were analyzed. We compared the morphology between patients and controls; examined their correlations to meibum expressibility, quality, and DESL. Relative to controls, the gland thickness, density and distortion were elevated in patients (p < 0.001 for all tests). The area under the receiver operating characteristic curve was 0.98 (95% confidence interval [CI], 0.96-1.0) for gland loss, and 0.96 (CI 0.91-1.0) for gland distortion, with a cutoff value of six distorted glands yielding a sensitivity of 93% and specificity of 97% for MGD diagnosis. The gland distortion was negatively correlated to the meibum expressibility (r = -0.53; p < 0.001) and DESL (r = -0.22, p = 0.018). In conclusion, evaluation of meibomian gland loss and distortion are valuable complementary clinical parameters to assess MGD status.

Characteristics and Utility of Fundus Autofluorescence in Congenital Aniridia Using Scanning Laser Ophthalmoscopy.

Purpose: To investigate fundus autofluorescence (FAF) and other fundus manifestations in congenital aniridia. Methods: Fourteen patients with congenital aniridia and 14 age- and sex-matched healthy controls were examined. FAF images were obtained with an ultra-widefield scanning laser ophthalmoscope. FAF intensity was quantified in the macular fovea and in a macular ring surrounding fovea and related to an internal reference within each image. All aniridia patients underwent an ophthalmologic examination, including optical coherence tomography and slit-lamp biomicroscopy. Results: Mean age was 28.4 ± 15.0 years in both the aniridia and control groups. Fovea could be defined by subjective assessment of FAF images in three aniridia patients (21.4%) and in all controls (P = 0.001). Mean ratio between FAF intensity in the macular ring and fovea was 1.01 ± 0.15 in aniridia versus 1.18 ± 0.09 in controls (P = 0.034). In aniridia, presence of foveal hypoplasia evaluated by biomicroscopy correlated with lack of foveal appearance by subjective analyses of FAF images (P = 0.031) and observation of nystagmus (P = 0.009). Conclusions: Aniridia patients present a lower ratio between FAF intensity in the peripheral and central macula than do healthy individuals. Both subjective and objective analyses of FAF images are useful tools in evaluation of foveal hypoplasia in aniridia.

Tear Metabolomics in Dry Eye Disease: A Review.

Dry eye disease (DED) is a multifactorial syndrome that can be caused by alteration in the quality or quantity of the precorneal tear film. It is considered one of the most common ocular conditions leading patients to seek eye care. The current method for diagnostic evaluations and follow-up examinations of DED is a combination of clinical signs and symptoms determined by clinical tests and questionnaires, respectively. The application of powerful omics technologies has opened new avenues toward analysis of subjects in health and disease. Metabolomics is a new emerging and complementary research discipline to all modern omics in the comprehensive analysis of biological systems. The identification of distinct metabolites and integrated metabolic profiles in patients can potentially inform clinicians at an early stage or during monitoring of disease progression, enhancing diagnosis, prognosis, and the choice of therapy. In ophthalmology, metabolomics has gained considerable attention over the past decade but very limited such studies have been reported on DED. This paper aims to review the application of tear metabolomics in DED.

Proteomic and histopathological characterisation of sicca subjects and primary Sjögren's syndrome patients reveals promising tear, saliva and extracellular vesicle disease biomarkers.

BACKGROUND: Mononuclear cell infiltration of exocrine glands, production of Ro/SSA and La/SSB autoantibodies, along with oral and ocular dryness, are characteristic features of primary Sjögren's syndrome (pSS). Non-SS sicca subjects, an underexplored group in relation to pSS, display similar sicca symptoms, with possible mild signs of inflammation in their salivary glands, yet with no serological detection of autoantibody production. In this study, we investigated inflammatory manifestations in the salivary gland tissue, tear fluid and saliva of non-SS subjects, as compared to pSS patients and healthy individuals. METHODS: Fifteen non-SS, 10 pSS and 10 healthy subjects were included in the analyses. Histological evaluation of salivary gland biopsies was performed. Liquid chromatography-mass spectrometry (LC-MS) was conducted on tear fluid and stimulated whole saliva, and proteomic biomarker profiles were generated. Extracellular vesicle (EVs) isolation and characterisation from both fluids were also combined with LC-MS. The LC-MS data were analysed for quantitative differences between patient and control groups using Scaffold. Database for Annotation, Visualization and Integrated Discovery (DAVID) and Functional Enrichment Analysis Tool (FunRich) were applied for functional analyses. RESULTS: Histopathological evaluation of salivary gland biopsies showed implications of milder inflammation in non-SS subjects through mononuclear cell infiltration, fibrosis and fatty replacement, as compared to pSS patients. Although unaffected in the non-SS group, upregulation of proinflammatory pathways and proteins involved in ubiquitination (LMO7 and HUWE1) and B cell differentiation (TPD52) were detected in tear fluid of pSS patients. Moreover, overexpression of proteins STOM, ANXA4 and ANXA1, regulating cellular innate and adaptive immunological pathways, were further identified in EVs from tear fluid of pSS patients. Finally, whole saliva and EVs isolated from whole saliva of pSS patients expressed proteins vital for innate MHC class I cellular regulation (NGAL) and T cell activation (CD44). CONCLUSIONS: Non-SS sicca subjects may show implications of mild inflammation in their glandular tissue, while their protein profile was strikingly more similar to healthy controls than to pSS patients. Hence, the tear and salivary biomarkers identified could be implemented as potential non-invasive diagnostic tools that may aid in increasing diagnostic accuracy when evaluating non-SS subjects and pSS patients and monitoring disease progression.

The Cone Photoreceptor Mosaic in Aniridia: Within-Family Phenotype-Genotype Discordance.

PURPOSE: Investigate in vivo cone photoreceptor structure in familial aniridia caused by deletion in the PAX6 gene to elucidate the complexity of between-individual variation in retinal phenotype. DESIGN: Descriptive case-control study. PARTICIPANTS: Eight persons with congenital aniridia (40-66 yrs) from 1 family and 33 normal control participants (14-69 yrs), including 7 unaffected family members (14-53 yrs). METHODS: DNA was isolated from saliva samples and used in polymerase chain reaction analysis to amplify and sequence exons and intron or exon junctions of the PAX6 gene. High-resolution retinal images were acquired with OCT and adaptive optics scanning light ophthalmoscopy. Cone density (CD; in cones per square millimeter) and mosaic regularity were estimated along nasal-temporal meridians within the central 0° to 5° eccentricity. Horizontal spectral-domain OCT line scans were segmented to analyze the severity of foveal hypoplasia (FH) and to measure retinal layer thicknesses. MAIN OUTCOMES AND MEASURES: Within-family variability in macular retinal layer thicknesses, cone photoreceptor density, and mosaic regularity in aniridia compared with normal control participants. RESULTS: DNA sequencing revealed a known PAX6 mutation (IV2-2delA). Those with aniridia showed variable iris phenotype ranging from almost normal appearance to no iris. Four participants with aniridia demonstrated FH grade 2, 2 demonstrated grade 3 FH, and 1 demonstrated grade 4 FH. Visual acuity ranged from 0.20 to 0.86 logarithm of the minimum angle of resolution. Adaptive optics scanning light ophthalmoscopy images were acquired from 5 family members with aniridia. Foveal CD varied between 19 899 and 55 128 cones/mm2 with overlap between the foveal hypoplasia grades. Cone density was 3 standard deviations (SDs) or more less than the normal mean within 0.5°, 2 SDs less than the normal mean at 0.5° to 4°, and more than 1 SD less than the normal mean at 5° retinal eccentricity. CONCLUSIONS: The results showed considerable variability in foveal development within a family carrying the same PAX6 mutation. This, together with the structural and functional variability within each grade of foveal hypoplasia, underlines the importance of advancing knowledge about retinal cellular phenotype in aniridia.