Computer aided volumetric assessment of orbital structures in patients with Graves' orbitopathy: correlation with serum thyroid antiperoxidase antibodies and disease activity.

INTRODUCTION: Graves' disease is an autoimmune disorder. Goiter and Graves' orbitopathy are frequently seen clinically. It would be helpful for the diagnosis, grading, prognosis, and treatment of this condition if it was possible to find serum biomarkers to establish a connection between the plasma levels of these compounds and orbital changes. METHODS: A retrospective study was performed by revising the medical records of 44 patients with Graves' orbitopathy and 15 controls. The Osirix software (Pixmeo, Geneva, Switzerland) was used for manual orbital measurements. Plasma levels of Graves' orbitopathy substances were obtained in the analytical review of the patients. RESULTS: A greater muscle volume was observed in patients with Graves' orbitopathy in relation to the control group (p < 0.001). The clinical activity score (CAS) was associated to total muscle mass (p = 0.013) and retrorbital fat (p = 0.048). Our results indicated a direct relationship between serum concentrations of anti-thyroid peroxidase antibodies and inferior rectus thickening (p = 0.036); however, we did not observe a positive correlation between other muscle volumes and serum concentrations of various thyroid-related substances. CONCLUSIONS: This study is the first that uses Osirix measurement software to manually assess orbital features in patients with Graves' orbitopathy. These measurements were compared to the outcomes of tests performed in a laboratory. Among several serum biomarkers, anti-thyroid peroxidase appears to be a reliable biomarker that correlates positively with inferior rectus muscle thickness in patients with thyroid eye disease. This may help to improve the management of this disease.

Inkjet drug printing onto contact lenses: Deposition optimisation and non-invasive dose verification.

Inkjet printing has the potential to advance the treatment of eye diseases by printing drugs on demand onto contact lenses for localised delivery and personalised dosing, while near-infrared (NIR) spectroscopy can further be used as a quality control method for quantifying the drug but has yet to be demonstrated with contact lenses. In this study, a glaucoma therapy drug, timolol maleate, was successfully printed onto contact lenses using a modified commercial inkjet printer. The drug-loaded ink prepared for the printer was designed to match the properties of commercial ink, whilst having maximal drug loading and avoiding ocular inflammation. This setup demonstrated personalised drug dosing by printing multiple passes. Light transmittance was found to be unaffected by drug loading on the contact lens. A novel dissolution model was built, and in vitro dissolution studies showed drug release over at least 3 h, significantly longer than eye drops. NIR was used as an external validation method to accurately quantify the drug dose. Overall, the combination of inkjet printing and NIR represent a novel method for point-of-care personalisation and quantification of drug-loaded contact lenses.

ULTRASONOGRAPHIC FINDINGS IN THE VITREOUS OF PATIENTS WITH AGE-RELATED MACULAR DEGENERATION TREATED WITH INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR INJECTIONS.

PURPOSE: We aimed to assess the relationship of repeated intravitreal injection of anti-vascular endothelial growth factor, the main treatment for exudative age-related macular degeneration, with changes in vitreous ultrasonographic findings in patients with age-related macular degeneration. METHODS: We retrospectively collected data from 41 patients (41 age-related macular degeneration eyes, 41 control eyes) on age, sex, number of injections, and type of anti-vascular endothelial growth factor (ranibizumab, aflibercept). Ocular ultrasonography was performed with open eyelids, under topical anesthesia, and using carbomers as ultrasonographic gel. Topographic, quantitative, and kinetic ultrasonography was performed in all eye quadrants using a 10-MHz posterior pole probe, and vitreous reflectivity was assessed. RESULTS: The mean age of patients was 79 (range: 59-94) years, with a mean of five intravitreal anti-vascular endothelial growth factor injections (range: 1-13). No significant ultrasonographic differences were found relative to the incidence of partial or complete posterior vitreous detachment. Vitreous hyperechogenicity increased in the treated eye (P < 0.001), and the vitreous reflectivity range increased with the number of injections (P = 0.041, R = 0.214). However, the type of anti-vascular endothelial growth factor used and the time elapsed since the last intravitreal injection was not significant (P > 0.05). CONCLUSION: These preliminary results indicate a proportional increase in ultrasonographic reflectivity of vitreous gel with the number of injections.

Intravitreal injections of anti-VEGF agents and antibiotic prophylaxis for endophthalmitis: A systematic review and meta-analysis.

We performed a systematic review and meta-analysis to determine whether the use of local antibiotics is a beneficial prophylactic treatment for endophthalmitis in patients treated with anti-VEGF agents. We searched the MEDLINE and EMBASE databases, and the Cochrane Library over the period January 2007 to December 2016. The search terms used included "Endophthalmitis", "Antibiotic" and "Intravitreal injection". Studies in which the patients were treated exclusively with intravitreal injections of anti-VEGF were selected. Eight studies fit the inclusion criteria, which included a total of 276,774 injections; 109,178 (39.45%) were associated with the use of antibiotics and 114,821 (60.55%) were not associated with the use of antibiotics. Our meta-analysis indicated a significant risk for endophthalmitis that was 1.70 times greater with the use of antibiotics than that without antibiotics, with a confidence interval of 1.08 to 2.66 (p = 0.02). A meta-regression indicated that the location (operating rooms versus outpatient clinics) of injection did not have a significant effect on the incidence of endophthalmitis. The prophylactic use of antibiotics when administering anti-VEGF intravitreal injections may contribute to a greater incidence of endophthalmitis. This finding, in addition to reducing costs, would eliminate a treatment that has been shown to be unnecessary and even harmful to patients.

EVALUATION OF VITRECTOMY AND REIMPLANTATION FOLLOWING LATE DISLOCATION OF THE INTRAOCULAR LENS-CAPSULAR BAG COMPLEX: A 3-Year Follow-up Study.

OBJECTIVES: To study the predisposition factors for dislocation of the intraocular lens (IOL)-capsular bag complex and analyze the results of subsequent reimplantation surgery. METHODS: The exclusion criteria were complicated cataract surgery and minor dislocations that appeared in the first year after cataract surgery. Thirty-six months of monitoring of the reimplantation surgery was required. The primary measurements of results were factors concerning dislocation, the interval between cataract surgery and dislocation, and postoperative complications. RESULTS: Thirty-six patients with dislocation of the capsular bag and lens were identified. Pseudoexfoliation was mentioned in 17 cases (47.2%) and was the main predisposition factor. The average interval between cataract surgery and dislocation was 11.5 years. The dislocated IOL was replaced by a posterior chamber implant in 38% of cases and an anterior chamber implant in 62%. The average best-corrected visual acuity improved significantly after the reposition surgery (P < 0.01). The average monitoring period after secondary reimplantation was 5.95 years (min. 3.03-max. 8.46). Three patients developed bullous keratopathy, all of them with an anterior chamber IOL implantation. CONCLUSION: According to our knowledge, this article is the one with the longest monitoring time to date. Pseudoexfoliation was the main risk factor for the dislocation of the IOL. Surgery significantly improved best-corrected visual acuity, and the reimplantation of the IOL in the posterior chamber was associated with less serious complications.

ME20-S as a Potential Biomarker for the Evaluation of Uveal Melanoma.

PURPOSE: We previously identified the presence of the melanocyte-specific secreted (ME20-S) glycoprotein in secretomes of uveal melanoma (UM) cultures. The aim of this study was to test for the presence and levels of ME20-S in the serum of patients with choroidal nevi and UM and correlate these levels with individual clinical data. METHODS: Serum ME20-S levels were determined by ELISA in 111 patients distributed into four categories (53 choroidal nevi, 30 untreated UM, 11 10-year disease-free [DF] UM, 17 hepatic metastatic UM) and 32 age- and sex-matched controls. ME20-S levels were correlated with individual clinical data. RESULTS: The UM and the metastatic groups showed significantly higher levels of serum ME20-S than the other groups (P < 0.001). ME20-S levels in the DF patients did not differ from those in the control group. In addition, log-transformed serum ME20-S levels showed a positive correlation with the thickness of the lesion mass in UM patients (regression coefficient 0.0689, 95% confidence interval 0.0689-0.1123, R2 = 27.1%). CONCLUSIONS: Elevated ME20-S serum levels are associated with tumor size and advanced stages of UM while low levels are characteristic of DF patients. ME20-S might be a promising serum marker for UM and useful for monitoring metastatic disease.

Acute loss of vision after an intravitreal injection ocriplasmin: a functional evolutionary study for 1-year follow-up.

INTRODUCTION: Ocriplasmin is a human plasmin fragment indicated for vitreomacular traction treatment. With its increasing use, several reported cases have suggested possible toxicity to the retina. CASE: We describe a case of a 55-year-old woman with symptomatic vitreomacular traction and a macular hole in the right eye who showed an acute decrease in visual acuity after an intravitreal ocriplasmin injection. Spectral-domain optical coherence tomography showed an alteration in the ellipsoid layer. Significant retinal vessel constriction was observed by angiography. The visual acuity improved to 20/100, and the electroretinogram progressively improved after the 1-year follow-up and following pars plana vitrectomy. CONCLUSIONS: A decrease in visual acuity and an enlargement of the macular hole were observed while studying this patient. This study shows the recovery of adverse effects caused by intravitreal injection of ocriplasmin for 1-year follow-up.

Detection of circulating melanoma cells in choroidal melanocytic lesions.

PURPOSE: To detect and quantify circulating tumour cells (CTCs) in peripheral blood of patients with uveal melanoma primary non-metastatic tumours, and to analyze the possible relationship between CTCs and clinical risk factors. METHODS: Prospective study with two clinical groups: 4 patients diagnosed with choroidal nevus and 8 patients with choroidal melanoma prior to treatment. A single sample of 7.5 mL of peripheral blood was taken and the CTCs were isolated using a CellSearch system that captures positive cells for the CD146 antigen (MUC18). RESULTS: None of the patients with choroidal nevus showed CTCs in peripheral blood. More than one CTC/7.5 mL was detected in 50 % of patients with choroidal melanoma prior to treatment. The higher level of CTC cells in peripheral blood (3/7.5 mL) was detected in the patient with the larger choroidal melanoma which also presented extrascleral extension and epithelioid pathology. CONCLUSION: Performing an analysis with the CellSearch system allows to quantify the choroidal melanoma CTCs in peripheral blood. This finding highlights the potential usefulness of this technique to achieve the correct stratification and monitoring of the treatment.

Serum DJ-1/PARK 7 is a potential biomarker of choroidal nevi transformation.

PURPOSE: There is substantial evidence that intraocular melanomas arise from benign nevi in the uveal tract. Previous studies performed by the authors revealed that uveal melanoma cells secrete the oncoprotein DJ-1/PARK7 into the extracellular environment and circulation. The aim of this study was to determine whether circulating DJ-1 serum levels correlate with known clinical risk factors of nevi growth. METHODS: Standardized ultrasonography, optical coherence tomography, and eye fundus examinations were used to evaluate the clinical risk factors of nevi growth. These clinical risk factors (including nevi size, distance of margins to the optic disc, detection of acoustic hollowness, presence of ocular symptoms, orange pigment, subretinal fluid, and absence of drusen) were examined in 53 consecutive patients from January 2009 to February 2011. Serum levels of DJ-1/PARK7 in these patients and in healthy age- and sex-matched controls (n = 32) were analyzed using ELISA. RESULTS: Within the choroidal nevi group, DJ-1 serum levels were higher in those with symptoms (P < 0.033), with a nevus thickness greater than 1.5 mm (P < 0.001), a large basal diameter greater than 8 mm (P < 0.001), and the presence of acoustic hollowness (P < 0.001), compared to those patients without these risk factors. Similar significant differences were found when these at risk nevi subgroups were compared to healthy persons. CONCLUSIONS: Elevated serum levels of DJ-1 are associated with choroidal nevi transformation risk factors. Therefore, DJ-1 appears to be a promising factor for predicting the growth of choroidal nevi and may be a potential biomarker of malignancy.