Interobserver Reliability and Sensitivity to Change of a Composite Ocular Inflammatory Activity Index: UVEDAI©.

INTRODUCTION: This was a multicenter, prospective, longitudinal, observational study involving eight Spanish tertiary hospitals to determine the interobserver reliability of an uveitis disease activity index, (UVEDAI) and assess its sensitivity to change in patients with receiving pharmacologic treatment. METHODS: Patients aged ≥ 18 years diagnosed with active noninfectious uveitis were included. A complete baseline assessment was performed by two ophthalmologists who determined ocular inflammatory activity using the UVEDAI index independently of each other. The principal ophthalmologist made a new visit at 4 weeks to determine the change in inflammatory activity. The interobserver reliability analysis was performed by calculating the intraclass correlation coefficient (ICC), with the values of the variables and the UVEDAI obtained by both ophthalmologists in the more active eye at the baseline visit. Sensitivity to change in the UVEDAI index was assessed at 4 weeks from the start of pharmacologic treatment by determining the clinically relevant change, defined as a change in UVEDAI of ≥ 0.8 points over baseline. The mean change between both measures was compared using the repeated-measures t-test. RESULTS: A total of 111 patients were included. In the interobserver reliability analysis, the ICC for the UVEDAI value was 0.9, and, when compared with the mean UVEDAI values obtained by the ophthalmologists, no statistically significant differences were found (p value > 0.05). As for the sensitivity to change in UVEDAI, statistically significant differences (p value = 0.00) were found for the mean values of the index compared with baseline. In all cases, the index value decreased by > 1 point at the 4-week visit. CONCLUSIONS: The interobserver reliability of the UVEDAI was high in the total sample. Furthermore, the index was sensitive in determining the change in inflammatory activity after treatment. We believe that UVEDAI is a disease activity index that enables objective comparison of results in clinical practice and trials.

Validation of UVEDAI: An Index for Evaluating the Level of Inflammatory Activity in Uveitis.

INTRODUCTION: Uveitis is the inflammation of the middle layer of the eye, the uvea, and is a major cause of blindness. None of the instruments used in clinical practice are, in themselves, sufficient to evaluate the course of uveitis. Therefore, it is necessary to develop instruments enabling standardized measurement of inflammatory activity. We developed a composite disease activity index for patients with uveitis known as UVEDAI, which considers the overall activity of the eye. The objective of this study was to validate the composite index of ocular inflammation, UVEDAI. METHODS: A multicenter cross-sectional study involving eight Spanish tertiary hospitals. Sixty-two patients aged ≥ 18 years with acute uveitis were recruited. Participants gave informed consent before participating in the study. A full ophthalmological examination was performed by two ophthalmologists to determine inflammatory activity: one used the UVEDAI score and the other used clinical judgment. The ophthalmologists did not share their findings with each other to avoid introducing bias into the analysis. Construct validity was established by means of factor analysis. The criterion validity of the index was determined using an ordinal multivariate regression model, in which the dependent variable was the degree of uveal inflammation (mild, moderate, or high/severe). Cut-off points were determined for the UVEDAI and for the receiver operating characteristic (ROC) curves. RESULTS: Sixty-two patients were included. Total variance with the three components accounted for 80.32% of the construct validity. Each of the three components identified one type of eye involvement. The discriminatory capacity of UVEDAI was 0.867 (95% CI 0.778; 0.955 p < 0.001) for mild versus moderate-high and 0.946 (95% CI 0.879; 1.000 p < 0.001) for high versus mild-moderate. CONCLUSIONS: The variables included in UVEDAI enable ocular inflammatory activity to be described with a high degree of accuracy. The index may be used to evaluate and classify this activity with considerable discriminatory power.

Measuring Choroid Thickness as a Marker of Systemic Inflammation in Patients With Ankylosing Spondylitis.

BACKGROUND AND OBJECTIVE: Ankylosing spondylitis (AS) is an inflammatory disease, and choroidal thickness (CT) has been proposed and evaluated as a potential marker of systemic inflammation associated with AS and other inflammatory diseases. This study compared CT measurements taken from patients with severe AS disease activity without eye inflammation with those taken from healthy subjects. METHODS: This cross-sectional, multicenter study compared CT in 44 patients with high AS disease activity, and no history of eye inflammation with CT in 44 matched healthy subjects aged between 18 and 65 years. In the AS group, the correlation between CT and C-reactive protein, human leukocyte antigen (HLA) B27 positivity, disease duration, and disease activity was calculated. RESULTS: Mean CT values of patients with AS were significantly higher in the right eye, the left eye, and the thickest choroid eye. The right eye mean CT was 338.3 ± 82.8 µm among patients with AS and 290.5 ± 71.2 µm among healthy subjects (p = 0.005). The left eye mean CT was 339.5 ± 84.7 µm for patients with AS and 298.4 ± 68.9 µm for healthy subjects (P = 0.015). The thickest choroid eye CT was 358.4 ± 82.1 µm among patients with AS and 314.1 ± 65.2 µm among healthy subjects (P = 0.006). We did not find a significant correlation between CT and disease activity, C-reactive protein, human leukocyte antigen B27 positivity, or disease duration. CONCLUSIONS: Patients with active AS but without a history of eye inflammation had a thicker choroid than healthy subjects. This finding suggests that CT is a marker of systemic inflammation in patients with inflammatory disease, regardless of known eye symptoms.

Lyophilized Autologous Serum Eyedrops: Experimental and Comparative Study.

PURPOSE: To analyze the biological stability of autologous serum eyedrops after lyophilization. DESIGN: Prospective, comparative experimental study. METHODS: This was a comparative study with serum obtained from 12 healthy volunteers. The concentrations of different epitheliotropic factors (eg, transforming growth factor-ß [TGF-ß1], epidermal growth factor [EGF], platelet-derived growth factor AB [PDGF-AB], and albumin) were measured in fresh and lyophilized serum. The samples were studied after serum preparation (fresh serum) and immediately after saline solution reconstitution of lyophilized serum (0), 15, and 30 days later. The biological effects of both serum samples were also compared on conjunctival and corneal cell cultures. The pH, osmolarity, and serum density were also determined. RESULTS: No significant differences were found in the concentration of growth factors between fresh serum and re-dissolved serum samples after lyophilization. The concentration of growth factors remained stable during 1 month at 4°C in re-dissolved lyophilized form with saline solution. No differences were found related to osmolarity, pH, and density between fresh and lyophilized serum. In addition, no differences were found on the conjunctival and corneal cells proliferation and differentiation in cells cultures between either serum preparation. CONCLUSIONS: The properties of autologous serum remain after lyophilization. The lyophilized serum can be easily stored without temperature restrictions and easily reconstituted for preparation of eyedrops for standard clinical use.

Choroidal Thickness Is a Biomarker Associated With Response to Treatment in Ankylosing Spondylitis.

OBJECTIVE: Choroidal thickness (CT) has been evaluated as a marker of systemic inflammation in ankylosing spondylitis (AS). This study evaluates the CT of AS patients before and after 6 months of biological treatment. METHODS: This longitudinal multicenter study evaluated CT in 44 AS patients. The correlations between CT and C-reactive protein (CRP) with disease activity indices were calculated. The concordance between CT and CRP was determined. We assessed factors associated with response to treatment. Clinically important improvement was defined as a decrease in Ankylosing Spondylitis Disease Activity Score of 1.1 points or greater. RESULTS: Forty-four eyes in patients aged 18 to 65 years were included. Mean CT values were significantly higher at baseline than after 6 months of treatment (baseline: 355.28 ± 80.46 µm; 6 months: 341.26 ± 81.06 µm; p < 0.001). There was a 95% concordance between CT and CRP at baseline and 6 months. Clinically important improvement was associated with lower baseline CT and age as independent factors (odds ratios, 0.97 [95% confidence interval, 0.91-0.93; p = 0.009] and 0.81 [95% confidence interval, 0.7-0.95; p = 0.005]), with baseline CT of less than 374 µm (sensitivity 78%, specificity 78%, area under the curve 0.70, likelihood ratio 3.6). CONCLUSIONS: Choroidal thickness decreased significantly after 6 months of biological treatment in all treatment groups. Choroidal thickness and CRP had a 95% concordance. A high CT was associated with a risk of biological treatment failure. Choroidal thickness can be considered a useful biomarker of inflammation and a factor associated with response to treatment in AS.

Changes in Corneal Expression of MUC5AC after Autologous Serum Eyedrop Treatment in Patients with Limbal Stem Cell Deficiency.

Purpose: To evaluate the effect of autologous serum eyedrops treatment on corneal expression of the MUC5AC in patients with limbal deficiency. Methods: A prospective and comparative interventional case series study of 42 eyes of 21 patients was performed before and 8 weeks after treatment with autologous serum. All patients underwent a complete ophthalmic assessment of the tear film and ocular surface, corneal impression cytology (IC) and MUC5AC detection by Reverse Transcription-Polymerase Chain Reaction (RT-PCR). Results: Forty-one of the 42 eyes studied were available for both conventional cytology and MUC5AC analysis prior to and after treatment. Differences between outcomes obtained by impression cytology and MUC5AC detection were found in 9 of 82 samples (11%). We found changes in the corneal expression of MUC5AC after treatment in 19 of 41 eyes (46.3%): 18 of them (94.7%) changed from positive to negative expression, and 1 eye (5.3%) changed from negative to positive MUC5AC expression after autologous serum eyedrops. These changes were related with the corneal involvement prior to treatment (15 of them (78.9%) occurred in patients with slight corneal involvement), and with the improvement in the degree of squamous metaplasia after treatment (P = .001 and P = .003, respectively). Conclusions: The treatment significantly improved tear stability, squamous metaplasia, and subjective patient perception. Autologous serum eyedrops treatment diminished the corneal expression of MUC5AC mainly in patients with slight corneal involvement before treatment.

Modified lateral tarsal strip for involutional entropion and ectropion surgery.

PURPOSE: Our purpose was to assess our outcomes in involutional lower eyelid ectropion and entropion surgery after horizontal eyelid tightening by a modified tarsal strip technique. METHODS: A prospective study of 88 eyelids with ectropion and 96 with entropion was performed. Patients were randomly distributed into two groups: the control group included 90 eyelids (46 entropion and 44 ectropion) and the other group of 94 eyelids (50 entropion and 44 ectropion). The control group was treated with a conventional tarsal strip, whereas the second group underwent the same surgery except for a modified suture placement of the tarsal strip different in patients with ectropion and entropion. The mean follow-up was 5.4 years. Horizontal eyelid laxity, orbicularis muscle and lower eyelid retractors function were measured prior and after surgery. Recurrence rate was also evaluated. RESULTS: Recurrent entropion occurred in eight eyelids (17.4 %) treated with conventional tarsal strip, while only two eyelids (4 %) showed recurrence after surgery in the group treated with the modified technique. Recurrence ectropion was only found in one eyelid (2.3 %) in the control group. Pathological horizontal laxity was present in all patients at the baseline study. After surgery, the horizontal laxity improved in both groups, we found significant differences in the patients treated with the modified technique (P=0.04). CONCLUSIONS: The modified suture placement of the tarsal strip reported in this work improves the lower eyelid stability and prevents future recurrences after surgery. This modified technique is useful for the management of patients with entropion and moderate eyelid dysfunction retractors without other surgical procedures.

Effects of Autologous Serum Eye Drops on Conjunctival Expression of MUC5AC in Patients With Ocular Surface Disorders.

PURPOSE: To assess the effects of autologous serum eye drops on conjunctival expression of the mucin gene MUC5AC by means of quantitative reverse transcription polymerase chain reaction (RT-qPCR). METHODS: A prospective and comparative interventional case series study of 38 eyes of 19 patients with different ocular surface disorders was performed before and 6 weeks after the treatment with autologous serum eye drops. All patients underwent a complete ophthalmic assessment, including evaluation of the tear film, ocular surface exploration, conjunctival impression cytology (IC), and MUC5AC detection by reverse transcription polymerase chain reaction. RESULTS: A total of 34 eyes were studied by IC and MUC5AC quantitative reverse transcription polymerase chain reaction before and after treatment with autologous serum. This treatment improved breakup time, conjunctival squamous metaplasia, goblet cell density, and subjective perception in 76.2%, 70.6%, 55.9% and 73.5% of eyes, respectively. Treatment with autologous serum enhanced conjunctival expression of MUC5AC (P = 0.001), although these differences were not statistically significant if data are analyzed patient by patient (P = 0.09). In 13 of 34 eyes (38.2%), we found increased expression of MUC5AC; in 12 eyes (35.3%), no significant changes were found; and in 9 eyes (26.5%), a decreased expression was found. The MUC5AC gene upregulation was related to the conjunctival involvement before treatment and with the improvement in the degree of squamous metaplasia and the increase in the number of goblet cells in IC after treatment (P = 0.001). CONCLUSIONS: Treatment with autologous serum enhances the conjunctival expression of MUC5AC by increasing the density of goblet cells, mainly in patients with severe conjunctival involvement.

Stability of Growth Factors in Autologous Serum Eyedrops After Long-Term Storage.

PURPOSE: The purpose of this study is to assess the stability of the growth factors (GF) in autologous serum eyedrops under different storage conditions. METHODS: The concentration of epidermal growth factor (EGF), transforming growth factor-ß (TGF-ß1), platelet-derived growth factor AB (PDGF-AB), and albumin was measured in fresh and defrosted samples of autologous serum under different storage conditions. The fresh and defrosted samples were cooled at 4 °C, and they were studied immediately after preparation, or after defrosting, and after 1, 2, 3, and 4 weeks. The concentration of GF was also assessed after 1, 3, 6, and 9 months at -20 °C. We also investigated how the different storage conditions influence the biological effects of autologous serum on conjunctival and corneal cell cultures. RESULTS: The concentration of EGF, TGF-ß1, PDGF-AB, and albumin remained stable over the 4 weeks at 4 °C, both in fresh and in defrosted samples. Likewise, no statistically significant differences were found between the GF concentration in fresh samples and after 1, 3, 6, and 9 months of freezing at -20 °C. Moreover, no differences were found on the cell proliferation and differentiation between cultured cells with fresh or defrosted samples after 4 weeks at 4 °C or after 1, 3, 6, or 9 months at -20 °C. CONCLUSIONS: Long-term storage of autologous serum eyedrops at -20 °C does not affect the concentration of GF, simplifies clinical logistics, and reduces the frequency of blood extractions from the patients.

Amniotic membrane transplantation in acute toxic epidermal necrolysis: histopathologic changes and ocular surface features after 1-year follow-up.

PURPOSE: To evaluate ocular features and histopathologic changes in patients with toxic epidermal necrolysis (TEN) treated with amniotic membrane transplantation (AMT) in the acute phase. METHODS: A prospective study of 5 eyes (3 patients) with severe ocular involvement and 4 eyes (2 patients) with moderate involvement treated with AMT in the acute phase of TEN was performed. Patients underwent a complete ophthalmic assessment before the intervention and 3, 6, 9, and 12 months postoperatively. Tear film break-up time (BUT), Schirmer test, fluorescein_staining, corneal and conjunctival epithelial squamous metaplasia, ocular sequelae, and conjunctival retraction were measured. RESULTS: In patients with severe involvement, 2 eyes (40%) showed mild symblepharon and peripheral corneal neovascularization, and corneal epithelial defects, lid margin malposition, and trichiasis was found in 20% of the eyes; only 1 eye (20%) required surgery for structural defects. We did not find ocular sequelae after 1-year follow-up in the patients with moderate involvement. Only 1 eye (25%) developed mild symblepharon that did not require specific treatment. Amniotic membrane transplantation significantly improved the squamous metaplasia in corneal and conjunctival nonsecretory epithelial cells, and significantly improved the goblet cells density after 1-year follow-up. CONCLUSIONS: Amniotic membrane transplantation performed for acute TEN reduced inflammation and ocular surface scarring, improved dry eye and squamous metaplasia. and decreased ocular sequelae in the chronic stage. Although further and prospective studies are needed, AMT may be the optimal treatment for acute TEN with severe or moderate ocular involvement.

Autologous serum eye drops diluted with sodium hyaluronate: clinical and experimental comparative study.

PURPOSE: To assess the efficacy of sodium hyaluronate as vehicle for diluting autologous serum. METHODS: The concentration and temporal stability of EGF, TGF-ß, PDGF-AB and albumin in fresh and frozen samples of autologous serum diluted with sodium hyaluronate and saline solution, as well as the pH, osmolarity and density was studied. In parallel, the clinic effects of autologous serum diluted to 20% with sodium hyaluronate were compared with another solution of autologous serum diluted to 20% with saline in a prospective, comparative, randomized and double-blind study in 26 patients (52 eyes) with Sjögren syndrome. Patients underwent a complete ophthalmic assessment including tear film evaluation and corneal and conjunctival impression cytology at the beginning of the study and 2 months later. RESULTS: The growth factor (GF) concentration remained stable during 1 month at 4°C both in fresh and defrosted samples without any differences being found between both preparations. No differences were found related to osmolarity, pH and density between these preparations before and after frosting. Autologous serum diluted with sodium hyaluronate caused a significant improvement of the tear film stability, fluorescein and rose Bengal stain, break-up time, corneal and conjunctival squamous metaplasia as well as in the patient subjective perception. CONCLUSIONS: Sodium hyaluronate is an excellent vehicle for diluting autologous serum due to the gradual release of GF and increasing their duration and effect on the ocular surface. Preparations diluted with sodium hyaluronate are better tolerated by patients and require a lower number of drops administrations.

Use of containers with sterilizing filter in autologous serum eyedrops.

OBJECTIVE: To assess the effect of the use of containers with an adapted sterilizing filter on the contamination of autologous serum eyedrops. DESIGN: Prospective, consecutive, comparative, and randomized study. PARTICIPANTS: Thirty patients with Sjögren syndrome. METHODS: One hundred seventy-six autologous serum containers used in home therapy were studied; 48 of them included an adapted filter (Hyabak; Thea, Clermont-Ferrand, France), and the other 128 were conventional containers. Containers equipped with a filter were tested at 7, 14, 21, and 28 days of use, whereas conventional containers were studied after 7 days of use. In addition, testing for contamination was carried out in 14 conventional containers used during in-patient therapy every week for 4 weeks. In all cases, the preparation of the autologous serum was similar. Blood agar and chocolate agar were used as regular culture media for the microbiologic studies, whereas Sabouraud agar with chloramphenicol was the medium for fungal studies. MAIN OUTCOMES MEASURES: Microbiologic contamination of containers with autologous serum eyedrops. RESULTS: Only one of the containers with an adapted sterilizing filter (2.1%) became contaminated with Staphylococcus epidermidis after 1 month of treatment, whereas the contamination rate among conventional containers reached 28.9% after 7 days of treatment. The most frequent germs found in the samples were coagulase-negative Staphylococcus (48.6%). With regard the containers used in the in-patient setting, 2 (14.3%) became contaminated after 2 weeks, 5 (35.7%) became contaminated after 3 weeks, and 5 (50%) became contaminated after 4 weeks, leaving 7 (50%) that did not become contaminated after 1 month of treatment. CONCLUSIONS: Using containers with an adapted filter significantly reduces the contamination rates in autologous serum eyedrops, thus extending the use of such container by the patients for up to 4 weeks with virtually no contamination risks.

[Management of age-related macular degeneration. An update]. / Actualización en el manejo de la degeneración macular asociada a la edad.

Age-related macular degeneration is the leading cause of legal blindness in people over 50 in developed countries. It is a multifactorial disease resulting from the interaction of genetic and environmental factors, and the age is the only worldwide admitted risk factor. The socioeconomic impact of the disease reaches enormous proportions, if we take into account the high cost of the available antiangiogenic therapy, the strict schedule of medical visits that it requires, and the impairment that it gives rise to. The response to treatment and the visual outcomes improve with early management of the retinal lesions, thus the early diagnosis of the disease in its initial phases, based on self-control with an Amsler grid and with regular ophthalmologic assessments, is essential.

Histopathologic limbus evolution after alkaline burns.

PURPOSE: To study the histopathologic evolution of the corneal limbus after alkaline burns according to the clinical severity and therapy used. METHODS: A prospective study of 15 eyes from 12 patients (9 men and 3 women) with moderate and severe alkaline burns was performed. All patients were divided into 2 groups in accordance with the clinical ocular severity and the therapy that was used: medical therapy, amniotic membrane transplantation (AMT), autologous limbal transplantation (ALT), and ALT combined with AMT (ALT + AMT). Biopsies were obtained from affected limbal areas immediately after the ocular burn and 9 months later. RESULTS: Limbal regeneration was limited to small areas in patients with moderate burns treated with medical therapy; in contrast, the limbal structure showed significant stromal and epithelial regeneration in patients with moderate burns treated with AMT. There was an important stromal regeneration with an incomplete reepithelialization in patients with severe burns treated with AMT. Patients treated with ALT showed a good reepithelialization with a defective stromal regeneration. Epithelial and stromal regeneration was notable in patients with severe burns treated with ALT + AMT. CONCLUSIONS: In patients with moderate alkaline burns, AMT improved both limbal stromal and epithelial regeneration more effectively than medical therapy. In patients with severe burns, the best reepithelialization and stromal regeneration were obtained with ALT + AMT.