Corneal involvement in rheumatoid arthritis: an vivo confocal study

PURPOSE. To analyze the in vivo morphology of corneal cells and nerves in patients with rheumatoid arthritis (RA), with or without secondary Sj\uf6gren\u2019s syndrome (SSII), and to investigate the correlations between corneal alterations and RA activity. METHODS. Fifty patients with RA and 30 age- and gender-matched control subjects were studied. SSII was diagnosed according to the American-European Consensus Group criteria, and RA activity was evaluated by the Lansbury index (LI). Confocal microscopy was used to investigate corneal thickness, the number of epithelial and stromal cells, and keratocyte hyperreflectivity. In addition, the sub-basal plexus was assessed for the number, tortuosity, and reflectivity of the nerve fibers and the presence of beadlike formations. RESULTS. Sixteen percent of patients with RA also had SSII. Between the SSII and non-SSII groups, no significant differences were found in the LI or in the clinical and confocal variables. Significant differences were present between patients with RA and control subjects for all the variables studied except nerve reflectivity. In patients with RA with and without SSII, LI correlated significantly with the number of beadlike formations and the number of hyperreflective, activated keratocytes. CONCLUSIONS. Confocal microscopy of patients with RA showed several changes in corneal cells and nerves. The number of beadlike formations and the number of activated keratocytes could be interpreted as confocal signs of ocular surface disease activity. These correlations with the index of systemic disease activity, LI, may provide insight regarding the pathogenic mechanisms of dry eye in patients with RA

The cornea in Sjogren's syndrome : an in vivo confocal study

PURPOSE : To analyze the in vivo morphology of corneal cells and nerves in dry eye associated with primary (SSI) and secondary (SSII) Sj\uf6gren's syndrome and to study its relationship with the clinical evaluation. METHODS: Thirty-five patients with SS and 20 age- and gender-matched control subjects were studied. Confocal microscopy was used to investigate corneal thickness, epithelial and stromal cellular density, and subbasal plexus morphology. RESULTS : Corneal central thickness was 514.74 +/- 19.85 microm in the SS group and 550 +/- 21.46 microm in the control group (P < 0.0001, t-test); stromal central thickness was 456.62 +/- 18.05 microm in the SS group and 487.35 +/- 20.40 microm in the control group (P < 0.0001). The density of the superficial epithelial cells in the SSI and SSII groups was 965.40 +/- 96.00 and 999.80 +/- 115.67 cells/mm(2), respectively, and 1488.55 +/- 133.74 cells/mm(2) in the control group (P < 0.001, ANOVA). The number of subbasal nerves was 3.34 +/- 0.76 in the SS group and 5.10 +/- 0.79 in the control group (P < 0.0001, t-test). The average grade of nerve tortuosity was 2.62 +/- 0.94 in the SS group and 1.20 +/- 0.70 in the control group (P < 0.0001). Statistically significant correlations were found between clinical data and confocal microscopy data. CONCLUSIONS: Corneal thickness, cells, and nerves show morphologic changes in patients with dry eye associated with SS. The in vivo confocal study of these alterations may be important in better understanding the complexity of the ocular surface morphofunctional unit and the potentials of therapeutic approaches for the control of the phlogistic process and neuroprotectio

In vivo confocal microscopy of conjunctival roundish bright objects : young, older, and Sj\uf6gren subjects

PURPOSE. To investigate by laser scanning confocal microscopy (LSCM) the density of presumed epithelial, presumed goblet, and presumed inflammatory cells in the tarsal conjunctiva of healthy young and older subjects and in patients with Sjo\ua8gren\u2019s syndrome (SS). To evaluate the interobserver variability and to compare the measured densities with known age-related and SS-related changes. METHODS. The authors studied 24 eyes of 12 healthy young subjects (8 women, 4 men; average age, 26 years; age range, 21\u201330 years), 24 eyes of 12 healthy older subjects (10 women, 2 men; average age, 68 years; age range, 67\u201374 years), and 24 eyes of 12 patients with SS (10 women, 2 men; average age, 62 years; age range, 49\u201372 years). The inferior tarsal conjunctiva of each patient was examined in vivo by LSCM. The density of the three cell types was independently analyzed by two masked investigators. RESULTS. The density of presumed epithelial, presumed goblet, and presumed inflammatory cells was significantly higher in SS patients than in both control groups (P 0.001; Mann-Whitney U test). The densities for presumed goblet cells calculated by the two investigators were significantly different from one another (P 0.01, Mann-Whitney U test) and were not correlated. CONCLUSIONS. LSCM is a promising tool that should profoundly change the study of the ocular surface, but it requires accurate standardization before it is used in clinical practice

Corneal confocal microscopy in dry eye treated with corticosteroids

Purpose To evaluate, by in vivo laser scanning confocal microscopy (LSCM), the corneal findings in moderate-to-severe dry eye patients before and after treatment with topical corticosteroid and to associate the confocal findings to the clinical response. Methods Fifty eyes of 50 patients with moderate-to-severe dry eye were included in this open-label, masked study. Exclusion criteria were any systemic or ocular condition (other than dry eye) and any systemic or topical treatment (except artificial tears), ongoing or performed in the previous 3 months, with known effect on the ocular surface. All patients were treated with loteprednol etabonate ophthalmic suspension 0.5% qid for 4 weeks. Baseline and follow-up (day 30 \ub1 2) visits included Ocular Surface Disease Index (OSDI) questionnaire, full eye examination, and central cornea LSCM. We compared data obtained before and after treatment and looked for associations between baseline data and steroid-induced changes. Based on the previously validated OSDI Minimal Clinically Important Difference, we reanalyzed the baseline findings comparing those patients clinically improved after steroids to patients not clinically improved after steroids. Results Ocular Surface Disease Index score and LSCM dendritic cell density (DCD) significantly decreased after treatment. Baseline DCD correlated with both OSDI and DCD steroid-related changes (r = -0.44, p 2, p < 0.01; independent samples t test). Conclusions Laser scanning confocal microscopy examination of DCD allows detection of treatment-related inflammation changes and shows previously unknown associations between confocal finding and symptoms improvement after treatment. These promising preliminary data suggest the need for future studies testing the predictive value of DCD for a clinical response to topical corticosteroids

Functional and structural abnormalities in deferoxamine retinopathy : a review of the literature

Deferoxamine mesylate (DFO) is the most commonly used iron-chelating agent to treat transfusion-related hemosiderosis. Despite the clear advantages for the use of DFO, numerous DFO-related systemic toxicities have been reported in the literature, as well as sight-threatening ocular toxicity involving the retinal pigment epithelium (RPE). The damage to the RPE can lead to visual field defects, color-vision defects, abnormal electrophysiological tests, and permanent visual deterioration. The purpose of this review is to provide an updated summary of the ocular findings, including both functional and structural abnormalities, in DFO-treated patients. In particular, we pay particular attention to analyzing results of multimodal technologies for retinal imaging, which help ophthalmologists in the early diagnosis and correct management of DFO retinopathy. Fundus autofluorescence, for example, is not only useful for screening patients at high-risk of DFO retinopathy, but is also a prerequisite for identify specific high-risk patterns of RPE changes that are relevant for the prognosis of the disease. In addition, optical coherence tomography may have a clinical usefulness in detecting extent and location of different retinal changes in DFO retinopathy. Finally, this review wants to underline the need for universally approved guidelines for screening and followup of this particular disease

In vivo confocal microscopy of meibomian glands in Sj\uf6gren's syndrome

Purpose. To evaluate morphologic changes in meibomian glands (MGs) and the status of periglandular inflammation in patients with primary and secondary Sjogren's Syndrome (SS) using in vivo confocal laser microscopy (LSCM). Methods. Twenty patients with primary SS (SSI), 25 with secondary SS (SSII), 20 with MG dysfunction (MGD), and 25 age- and gender-matched control subjects were enrolled consecutively. Each participant completed an Ocular Surface Disease Index questionnaire and underwent a full eye examination, including tear film break-up time (BUT), fluorescein and lissamine green staining, Schirmer test, and an LSCM examination of the MGs, the last to determine acinar unit density and diameter, glandular orifice diameters, meibum secretion reflectivity, inhomogeneous appearance of glandular interstice, and acinar wall. Results. All parameters indicated statistically significant differences among groups (P < 0.001, Kruskal-Wallis test). LSCM demonstrated no differences between SSI and SSII (Mann-Whitney Utest). Compared with control subjects, SS subjects' MGs showed more periglandular inflammation and higher secretion reflectivity (P < 0.001, Mann-Whitney U test). Compared with MGD patients, SS patients' MGs had higher acinar density, smaller diameters, greater density of periglandular inflammatory cells, and lower secretion reflectivity (P < 0.001, Mann-Whitney U test). In SS patients, the two measured con-focal signs of inflammation were significantly interrelated and correlated with corneal fluorescein staining (P < 0.01, Spearman correlation coefficient). Acinar density and diameters were strongly correlated among themselves (P < 0.001) and with BUT (P < 0.05). Conclusions. LSCM is capable of effectively revealing morphologic and inflammatory changes in MGs and showed discernible patterns of MG abnormalities in SS and MGD not easily distinguishable by the usual clinical exams

Choroidal volume variations during childhood

Purpose. We analyzed choroidal volume (CV) variations during childhood using enhanced depth imaging optical coherence tomography, and evaluated its association with age, axial length (AXL), sex, weight, and height. Methods. Imaging studies of the right eyes of 52 healthy children were reviewed and included in this study. Subjects underwent a complete ocular examination and AXL measurement, as well as a raster macular scan using the Heidelberg Spectralis device. The choroid was segmented manually. Results. Subjects included 21 males and 31 females, with mean age of 9 years (range, 2-17 years) and mean AXL of 22.8 \ub1 0.98 mm. Mean CV was 0.263 \ub1 0.068 mm3 for the foveal circle and 8.545 \ub1 1.822 mm3 for the total Early Treatment of Diabetic Retinopathy Study (ETDRS) grid. The CV of the nasal quadrant was significantly lower than all others (P < 0.001). Total and foveal CV showed significant negative correlation with AXL after adjustment for age (P < 0.001), and significant positive correlation with age after adjustment for AXL (P < 0.001). Total CV was correlated significantly with sex after adjusting for AXL (P = 0.01), while no correlations were found between total CV and height or weight. The CV increased by 0.214 mm3 (2.5%) for every year, and decreased by 1.0 mm3 (11.7%) for every millimeter of axial length. Regression analysis confirmed a trend of higher CV in females than in males (P = 0.056). Conclusions. The CV increases with age during childhood, but decreases with AXL. This finding supports the hypothesis that the choroid grows progressively during childhood. Intersexual differences of CV also may be present

Corneal involvement in Graves' orbitopathy : an in vivo confocal study

PURPOSE: To study the clinical involvement of the ocular surface and the in vivo morphology of corneal cells and nerves, in patients affected by active and inactive Graves' orbitopathy (GO). METHODS: The study included 26 consecutive GO patients and 20 age- and sex-matched healthy control subjects. GO was diagnosed on the basis of the criteria of the European Group on Graves' Orbitopathy, and disease activity was evaluated by the Clinical Activity Score (CAS). Each participant underwent a full eye examination, including an evaluation of symptoms (Ocular Surface Disease Index score), tear break-up time, fluorescein and lissamine green staining, corneal apex sensitivity, and Schirmer's test. The corneal apex was examined by means of confocal microscopy to investigate the number and morphology of epithelial and stromal corneal cells and subbasal nerves. RESULTS: Eleven (43%) of the 26 patients had active GO. One-way ANOVA with the least-significant difference (LSD) post hoc test revealed statistically significant differences between patients and controls in all the evaluated parameters, except corneal sensitivity and nerve reflectivity. Among the GO patients, the only significant difference observed in active compared with inactive disease was in the number of hyperreflective (activated) keratocytes (P<0.001, LSD). Corneal sensitivity correlated inversely with proptosis (P<0.001, Spearman's test). CONCLUSIONS: GO patients show clinical and confocal corneal alterations and signs and symptoms partially related to dry eye disease. The ocular surface inflammation in GO seems to be due to both the dry eye and the autoimmune orbitopathy

Choroidal abnormalities detected by near-infrared reflectance imaging as a new diagnostic criterion for neurofibromatosis 1

Objective: To investigate in a large sample of consecutive patients with neurofibromatosis type 1 (NF1) the possibility of including the presence of choroidal abnormalities detected by near-infrared reflectance (NIR) as a new diagnostic criterion for NF1. Design: Cross-sectional evaluation of a diagnostic test. Participants and Controls: Ninety-five consecutive adult and pediatric patients (190 eyes) with NF1, diagnosed based on the National Institutes of Health (NIH) criteria. Controls included 100 healthy age- and gender-matched control subjects. Methods: Confocal scanning laser ophthalmoscopy was performed for each subject, investigating the presence and the number of choroidal abnormalities. Main Outcome Measures: Sensitivity, specificity, and diagnostic accuracy for the different cutoff values of the criterion choroidal nodules detected by NIR compared with the NIH criteria. Results: Choroidal nodules detected by NIR imaging were present in 79 (82%) of 95 of the NF1 patients, including 15 (71%) of the 21 NF1 pediatric patients. Similar abnormalities were present in 7 (7%) of 100 healthy subjects, including 2 (8%) of the 25 healthy pediatric subjects. The highest accuracy was obtained at the cutoff value of 1.5 choroidal nodules detected by NIR imagery. Sensitivity and specificity of the examination at the optimal cutoff point were 83% and 96%, respectively. Diagnostic accuracy was 90% in the overall population and 83% in the pediatric population. Both of these values were in line with the most common NIH diagnostic criteria. Conclusions: Choroidal abnormalities appearing as bright patchy nodules detected by NIR imaging frequently occurred in NF1 patients. The present study shows that NIR examination to detect choroidal involvement should be considered as a new diagnostic criterion for NF1