Miroslav Knežević

PREGO (presentation of Graves’ orbitopathy) study: changes in referral patterns to European Group On Graves’ Orbitopathy (EUGOGO) centres over the period from 2000 to 2012

Background/aims The epidemiology of Graves’ orbitopathy (GO) may be changing. The aim of the study was to identify trends in presentation of GO to tertiary centres and initial management over time. Methods Prospective observational study of European Group On Graves’ Orbitopathy (EUGOGO) centres. All new referrals with a diagnosis of GO over a 4-month period in 2012 were included. Clinical and demographic characteristics, referral timelines and initial decisions about management were recorded. The data were compared with a similar EUGOGO survey performed in 2000. Results The demographic characteristics of 269 patients studied in 2012 were similar to those collected in the year 2000, including smoking rates (40.0% vs 40.2%). Mild (60.5% vs 41.2%, p<0.01) and inactive GO (63.2% vs 39.9%, p<0.01) were more prevalent in 2012. The times from diagnosis of thyroid disease to being seen in EUGOGO centres (6 vs 16 months) and from first symptoms of GO (9 vs 16 months) or from diagnosis of GO (6 vs 12 months) to first consultation in EUGOGO centres were shorter in 2012 (p<0.01). The initial management plans for GO were no different except surgical treatments for patients with mild inactive disease were more frequently offered in the 2012 cohort than in 2000 (27.3% vs 17%, p<0.05), and selenium supplements were offered only in the 2012 cohort (21.2% vs 0%, p<0.01). Conclusions These findings suggest that the clinical manifestations of patients with GO may be changing over time in Europe.

Clinical significance of routine lacrimal sac biopsy during dacryocystorhinostomy: A comprehensive review of literature

The main purpose of this paper is to provide the information about the incidence and types of pathology of secondary acquired obstructions of the lacrimal excretory outflow system caused by primary lacrimal sac non-neoplastic and neoplastic lesions. After a thorough literature search, 17 case-control studies were found and selected, data were extracted and categorized, to evaluate specific lacrimal sac pathology mimicking inflammation. A total of 3865 histopathologically examined lacrimal sac wall biopsy specimens from 3662 patients, taken during dacryocystorhinostomy for clinically presumed primary chronic dacryocystitis, were analyzed. The most common reported histopathological finding was non-specific chronic inflammation with or without fibrosis (94.15% of cases). Lacrimal sac-specific pathologies were present in 226 (5.85%) cases. Unsuspected lacrimal sac-specific pathologies were present in 55/226 (24.34%) cases. Almost 45% of primary lacrimal sac malignant neoplasms were not suspected, preoperatively and intraoperatively. Tumor-like lesions of the lacrimal sac were the most common pathology found: (1) lacrimal stones-dacryoliths, (2) pyogenic granuloma, (3) granulation tissues, (4) reactive lymphoid hyperplasia, and (5) lacrimal sac-specific inflammation (Wegeners granulomatosis and sarcoidosis). Neoplastic pathology was found in 55/3865 (1.42%) lacrimal sac wall biopsy specimens; of those, malignant cases were 2.24 times more frequent than benign. Lymphoma was the most common preoperatively unsuspected or intraoperatively unexpected neoplastic pathology. This analysis of the relevant literature highlights the value of routine lacrimal sac biopsy during surgery for clinically presumed primary acquired nasolacrimal duct obstruction.

Comparison of postoperative pain and satisfaction after dacryocystorhinostomy in patients operated on under local and general anesthesia

Summary Background There has been only 1 study on postoperative pain after external dacryocystorhinostomy (DCR) that compared pain between 2 groups of patients; 1 group received local anesthesia and the other received general anesthesia. To further characterize the relationship between these 2 types of anesthesia and postoperative pain, we designed a study in which a single patient received these 2 different anesthesia modalities for a short interval on 2 different sides. Material/Methods There were 50 participants in this study. External DCR was performed on the same participant on both sides using local anesthesia on 1 side and general anesthesia on the other. Postoperative pain was measured using the visual analogue scale (VAS), and localization and timing of pain were reported by the participants. Postoperative nausea and vomiting (PONV) were documented if present. Results Pain levels were significantly higher with general anesthesia 3 hours post-surgery, and 6 hours post-surgery the pain remains higher following general anesthesia but is borderline insignificant (p=0.051). However, 12 hours post-surgery, there is no significant difference in the pain level (p=0.240). There was no significant difference in the localization of pain with local and general anesthesia. Postoperative nausea is significantly more frequent after general anesthesia, and vomiting only occurs with general anesthesia. Local anesthesia was preferred by 94% of the participants (47 out of 50). Conclusions The vast majority of patients in our study who have undergone both GA and LA DCR would choose LA again, providing a compelling case for use of the LA technique.

A 7-year prospective study of routine histopathological evaluation of the lacrimal sac wall incisional biopsy specimens obtained during external dacryocystorhinostomy in adults and a review of the literature.

The most common lacrimal sac pathology is chronic inflammation with or without occlusive fibrosis. However, a substantial number of lacrimal sac-specific pathologies were reported throughout the literature which may mimic chronic inflammation and be misdiagnosed. From a tertiary ophthalmic care centre in Serbia, in a single ophthalmic pathology laboratory, during a 7-year period (January 2004 to October 2010), a 599 consecutive lacrimal sac wall biopsy samples routinely obtained during external dacryocystorhinostomy in adult patients with clinically presumed primary acquired lacrimal drainage system obstruction were analysed. Although non-specific lacrimal sac pathology was present in the vast majority of cases (578 biopsy specimens; 96.49%), this report also reveals a relatively substantial number (21 biopsy specimens; 3.51%) of clinically non-suspected or intraoperatively unexpected primary lacrimal sac-specific pathology—among them, six lesions with malignant biological behaviour were identified: one microinvasive squamous cell carcinoma and five malignant lymhoproliferative lesions. Usefulness of routine lacrimal sac wall biopsy during surgery for primary acquired lacrimal drainage system obstruction is undoubtful and commensurate with the constant need for better understanding of the pathological processes that involve lacrimal drainage system.

Quantitation of brinzolamide in dried blood spots by a novel LC-QTOF-MS/MS method

In the current study, a rapid and sensitive LC-QTOF-MS/MS method for the determination of brinzolamide in dried blood spots (DBS) was developed and validated. This novel sample collection, storage and transfer technique was suitable for analyzing a drug with high distribution into red blood cells and negligible plasma levels. The method included an isocratic mobile phase consisting of methanol and 10mM ammonium formate (90:10, v/v) and detection in positive electrospray mode (ESI+). The flow rate was adjusted to 0.350mL/min yielding retention times of 1.7min for both brinzolamide and internal standard (IS) rabeprazole on a Cyano analytical column, respectively. The validation of the proposed method over the concentration range 0.500-20.0μg/mL was performed in compliance with EMEA and FDA guidelines, assessing all major performance characteristics. Inter- and intra- assay precisions were less than 14%, while inter- and intra- assay accuracies varied from 92.2 to 111%. No matrix effect was observed and the mean brinzolamide extraction recovery was 93.5%. The method was successfully applied to real DBS samples from patients in steady state condition, receiving brinzolamide ophthalmic suspension 1% (w/v) for several months. Initial concentrations were corrected due to hematocrit effect, using image processing algorithm written in Matlab.

Ocular pulse amplitude in patients with thyroid-associated ophthalmopathy

Purpose TO determine ocular pulse volume values in patients with thyroid-associated ophthalmopathy with normal intraocular pressure, and to test the hypothesis that changes in orbital tissue that accompany thyroid-associated ophthalmopathy can in turn give changes in choroidal perfusion. Methods In a prospective study, we evaluated 30 eyes of 30 consecutive patients with TAO, and 30 eyes of 30 healthy subjects. Complete ophthalmologic examination including dynamic contour tonometry was done. Possible differences in ocular parameters between the tested groups were assessed. Results NO significant difference was found in ocular pulse volume values between the tested subjects (paired test p=0.23). Conclusions The orbit tissue changes that are involved in thyroid-associated ophthalmopathy do not have much implication on choroidal perfusion, at least when intraocular pressure values remain within the normal range.

Acute post-surgical bilateral orbital gas-producing infection — a case report and literature review

The presence of visible gas on radiography, computed tomography (CT), or magnetic resonance imaging (MRI) is associated with various pathological conditions, ranging from severe infections caused by gas-producing organisms to cutaneous and subcutaneous tissue disruption that allows an interface with the air [1]. A high index of suspicion surrounds the finding of gas because of the virulence of conditions such as gas gangrene and necrotizing fasciitis [1–12]. Gas dissecting into the orbital soft tissues as a result of bacterial activity is a rapidly progressive, extremely serious, life-threatening ophthalmological emergency [1–12]. Gas gangrene (myonecrosis) and necrotizing fasciitis can cause necrosis of tissues and systemic shock with multiorgan failure, sometimes within a matter of hours [1–3, 13]. It is well known that the usual causative organisms in gas-producing infection from a contaminated wound are clostridial species: Clostridium perfringens accounts for the majority of cases (over 80 %), while most other cases are caused by other Clostridium species [1–3]. Clostridial infection is always associated with necrosis, and very often associated with poor functional and anatomical outcome [1–4]. However, a variety of other non-clostridial organisms, both aerobes and anaerobes, may also produce infections in which gas is demonstrable: Escherichia coli, Proteus species, Pseudomonas aeruginosa, Bacteroides, Klebsiela pneumoniae, Prevotella species, Staphylococcus aureus, Peptostreptococcus species, Fusobacterium species, and Streptococcus pyogenes are only the species reported most often in the literature [2]. Non-clostridial infections may take various forms, which lead to difficulties in making accurate and prompt diagnoses and are also related to the confusion between gas gangrene and various (bacterial and nonbacterial) lesions that simulate gas gangrene. Aside from the fact that non-clostridial organisms usually involve subcutaneous tissues, they may also involve muscle and simulate clostridial myonecrosis [2, 3]. However, non-clostridial gas infections accompanied by gangrene are not very common, even in immunosuppressed individuals [2, 3]. Since the initial report by Chiari (1893), which concerned a non-clostridial gas-forming infection due to a colon bacillus in the gangrenous lower limb of a diabetic patient [4], fewer than 40 cases of non-clostridial gas-forming infections have been described. Only four such cases have been described in the orbit [5–7, 12], and these are quite different from the present case. With regard to the pathogenesis of gas bubbles of clostridial or non-clostridial etiology, they are liberated by the bacterial fermentation of glucose [4]. In addition, impaired microcirculation may also contribute to gas formation [3, 4]. It is also necessary to mention the benign, non-infectious presence of gas in the orbit, which is known as orbital emphysema. Orbital emphysema is a well-known entity that can arise from nose-blowing, tumor presentation, or after fractures of the orbital floor, and may be self-induced in psychiatric patients [15]. There are no research contracts or any kind of financial support (grants) for this study. No authors have any conflicts of interest.