The prevalence and genotype of 21-hydroxylase deficiency in the Croatian Romani population.

Objective: Congenital adrenal hyperplasia (CAH) owing to 21-hydroxylase deficiency (21-OHD) is a rare autosomal recessive disorder caused by pathological variants in the CYP21A2 gene. After a high prevalence of classic 21-OHD CAH in the Romani population was reported in the Republic of North Macedonia, we decided to estimate the prevalence of 21-OHD in Croatia and, if high, assess the possible causes and estimate the frequency of particular CYP21A2 variants. Design: Cross-sectional study. Methods: Data from a Croatian 21-OHD genetic database was reviewed, and only Romani patients were included in the study. CYP21A2 genotyping was performed using allele-specific PCR, MLPA, and Sanger sequencing. Results: According to a survey conducted in 2017, Croatia had 22,500 Romani people and six of them had a salt-wasting (SW) form of 21-OHD. All were homozygous for the c.IVS2-13A/C-G pathological variant in intron 2 and descended from consanguineous families belonging to different Romani tribes. The calculated prevalence of 21-OHD in Croatian Romani is 1:3,750, while in the Croatian general population, it is 1:18,000. Three of the six Romani patients originated from two neighboring villages in North-western Croatia (Slavonia County), as well as the seventh patient who is of mixed Romani/Croatian descent and heterozygous for the c.IVS2-13A/C-G pathological variant (not included in the prevalence calculation). Conclusion: A high prevalence of SW 21-OHD in the Croatian Romani population caused by the homozygous cIVS2-13A/C-G pathological variant was found. In addition to isolation and consanguinity, other possible reasons could be the heterozygous advantage of the CYP21A2 gene pathological variant and the bottleneck effect as a result of the Romani Holocaust in World War II.

Characteristics, Risk Factors and Predictors for Candidemia in the Pediatric Intensive Care Unit at the University Hospital Centre Zagreb in Croatia: A 9-Year Retrospective Study.

BACKGROUND: Candidemia is one of the leading causes of bloodstream infections in the pediatric intensive care unit (PICU). The aim of this study was to define characteristics and risk factors for candidemia in the PICU setting and propose a predictive model to identify the patients at risk. METHODS: This was a retrospective matched case-control study in the PICU during a 9-year period. Patients with candidemia were studied and matched with control patients without candidemia. Univariate analysis was performed for potential risk factors and multivariate analysis was conducted to determine the prediction score for candidemia. RESULTS: Forty-two cases of candidemia were matched with 84 control patients. Candida parapsilosis was the most common (71.4%) species. Risk factors independently associated with candidemia were: the use of >2 antibiotics in a maximum period of 4 weeks before the candidemia (odds ratio [OR]: 10.59; 95% confidence interval [CI]: 2.05-54.83), a previous bacterial infection in a maximum period of 4 weeks before the candidemia (OR: 5.56; 95% CI: 1.44-21.5) and the duration of PICU stay of >10 days (OR: 4.22; 95% CI: 1.02-17.41). The proposed predictive scoring system has a sensitivity of 95.24%, specificity of 76.12%, OR 64.0, 95% CI 14.2-288.6, the positive predictive value of 66.67% and the negative predictive value of 96.97%. CONCLUSIONS: Previously reported risk factors for candidemia have been confirmed and some new have been detected. The presented scoring system can help identify patients who would benefit from prophylactic antifungal therapy.

THE ROLE OF FREQUENCY DOUBLING TECHNOLOGY PERIMETRY IN EARLY DETECTION OF DIABETIC RETINOPATHY.

The aim was to assess whether standard automated perimetry (SAP) and frequency doubling technology (FDT) perimetry are able to detect the effect of diabetes mellitus (DM) on retinal function in DM patients in the early stage of disease and to analyze which method is more specific and sensitive. A randomized cross-sectional study was conducted in three different groups of patients to compare the capability of these two methods to examine visual field and to detect the change in light sensitivity. Visual function was assessed in 60 adults with normal retinal finding, 60 adults with DM without clinically detectable retinopathy and 60 adults with DM and non-proliferative diabetic retinopathy but normal visual acuity. FDT perimetry and SAP were performed in all study patients. The presence and severity of diabetic retinopathy was determined by taking and evaluating two 50° field color photographs per eye, macula-centered and disc-centered. The following results were obtained by analyzing parameters in the groups of diabetic patients: sensitivity and specificity of SAP and FDT for medium sensitivity 86.7/33.3 (p<0.061) and 71.7/41.7 (p<0.228), respectively; for medium deficit 41.7/76.7 (p<0.063) and 65/50 (p<0.362), respectively; for loss of variance/pattern standard deviation (LV/PSD) 51.7/61.7 (p<0.536) and 61.7/51.7 (p<0.666), respectively; and for foveal sensitivity 81.7/36.7 (p<0.096) and 23.3/86.7 (p<0.839), respectively. Analysis of parameters between diabetics and control group yielded sensitivity and specificity for medium sensitivity 71.7/61.7 (p<0.001) and 70.8/55 (p<0.002), respectively; for medium deficit 56.7/60 (p<0.058) and 77.5/43.3 (p<0.037), respectively; for LV/PSD 58.3/58.3 (p<0.042) and 33.3/83.3 (p<0.437), respectively; and for foveal sensitivity 82.5/53.3 (p<0.001) and 28.3/85 (p<0.195), respectively. We concluded that neither of these methods was sensitive and specific enough to distinguish diabetics without retinopathy from diabetics with retinopathy. Both of these methods were highly specific and sensitive to distinguish diabetics from healthy subjects, but neither of these methods proved superior.

COMBINED TREATMENT WITH BEVACIZUMAB AND TRIAMCINOLONE ACETONIDE FOR MACULAR EDEMA DUE TO RETINAL VEIN OCCLUSION.

The purpose of this study was to determine the efficacy of combined intravitreal bevacizumab and triamcinolone in the treatment of macular edema due to retinal vein occlusion. A prospective randomized trial was conducted in the Department of Ophthalmology, Osijek University Hospital Centre in Osijek including 51 patients divided into three groups depending on the drug received. The first group received 1.25 mg intravitreal bevacizumab, the second group received 1 mg intravitreal triamcinolone, and the third group received a combination of 1.25 mg bevacizumab and 1 mg intravitreal triamcinolone on the same day. Changes in the central macular thickness, intraocular pressure and visual acuity were monitored during the follow up period. The retinal perfusion status was evaluated by fluorescein angiography. The group that received combined treatment had better outcome in terms of reduction of macular thickness. There was no statistically significant intraocular pressure elevation among the three treatment groups or within each group of patients. A positive trend regarding visual improvement was observed in the group receiving combined treatment in spite of the lowest initial visual acuity, highest value of macular thickness and longest mean duration of symptoms. In conclusion, combined treatment with bevacizumab and triamcinolone for the treatment of retinal vein occlusion is more potent, safe, efficient and cost-effective. It can also be recommended because fewer injections are needed in patients undergoing treatment for macular edema.

Protective Effect of Blepharospasm on the Anterior Segment of the Eye.

The aim of the study was to determine the role of blepharospasm as a protective factor for the anterior segment of the eye by comparing the degree of blepharospasm and changes of the anterior segment structures. The study included sixty female patients older than forty years with the clinical diagnosis of blepharospasm. They were divided into two groups; the first group consisted of patients with stage I and II of blepharospasm with dominant dry eye symptoms, and the second group consisted of patients with stage III and IV of blepharospasm who required interventional therapy (all patients in this study were treated with botulinum toxin type A). Staining of ocular surface with vital dyes such as fluorescein was used to determine ocular surface defects. Fluorescein stains the corneal epithelial defects, which were statistically less pronounced in the interventional group. In conclusion, comparison of the results between the two groups of patients may implicate that advanced blepharospasm has a protective effect on ocular surface.

Sensitivity of Diagnostic Tests for Dry Eye in Patients with Blepharospasm.

The aim of the study was to evaluate diagnostic tests for keratoconjunctivitis sicca (Schirmer test, tear break-up time (TBUT) test, and corneal staining with fluorescein and lissamine green dye) in patients with blepharospasm. This prospective study included 60 female patients older than 40 with blepharospasm, divided into two groups according to clinical symptoms. For fluorescein test, the surface under the ROC curve was 1.0 with standard error (SE) 0 and 95% confidence interval (95% CI) 0.940-1.0; for Schirmer test, the surface under the ROC curve was 0.817 with SE 0.0555 and 95% CI 0.696-0.905; for lissamine green test, the surface under the ROC curve was 0.813 with SE 0.056 and 95% CI 0.691-0.902; and for TBUT test, the surface under the ROC curve was 0.772 with SE 0.061 and 95% CI 0.645-0.870. According to the results of ROC curve, which determines the sensitivity and specificity of normal values, comparison of diagnostic tests for keratoconjunctivitis sicca used in this study showed that fluorescein test had the best sensitivity and specificity. Schirmer test should be avoided in patients with blepharospasm because its results are influenced by frequent blinking and are not appropriate for study interpretation. Despite the pathologic values of TBUT test (numerically), this test is still acceptable for patients with blepharospasm because its interval takes more time than the interval between two blinks.

Retinal Nerve Fiber Layer Thickness in Glaucoma Patients Treated with Multiple Intravitreal Anti-Vegf (Bevacizumab) Injections.

Over the past decade, intravitreal injections of anti-VEGF agents have been widely used and intensively developed as a treatment option for many ophthalmological indications. Due to its availability and low cost, the most frequently used anti-VEGF agent is bevacizumab. This type of therapy is often indicated in patients with exudative age-related macular degeneration (ARMD) and diabetic macular edema (DME). If, in addition to these two conditions, patients have a diagnosis of primary open angle glaucoma (POAG), they also present with optic nerve head (ONH) retinal nerve fiber layer (RNFL) thinning. The aim of this prospective study was to establish whether administering bevacizumab to patients with POAG leads to additional reduction of RNFL thickness. The study included 60 patients divided into two groups. First group comprised the eyes of patients with exudative ARMD and POAG, whereas second group comprised the eyes of patients with DME and POAG, all treated with bevacizumab. Control group comprised the fellow eye of each involved patient, which was not treated with bevacizumab. In a period of one year, all patients underwent optical coherence tomography (OCT) measurements of ONH RNFL thickness. The results of all patients were compared between the two study groups and then with control group results. Study results showed a decrease of RNFL in both groups of patients. Comparison of these two groups of patients after one year revealed a statistically more significant decrease in RNFL thickness in the second group (DME + POAG).

Influence of silicone oil tamponade after vitrectomy on intraocular pressure.

The aim of this prospective study was to determine the possible influence of the silicone oil tamponade after vitrectomy on the early intraocular pressure (IOP) elevation, which is a major risk factor for developing secondary glaucoma in patients with vitreal and retinal proliferative changes. The research included 110 patients which were allocated in three groups according to the medical history data. The surgical procedures were performed at the Eye Clinic, University of Zagreb School of Medicine. The control group comprised 40 patients who underwent vitrectomy with air or saline solution tamponade. The second group consisted of 40 patients with retinal detachment and proliferative retinopathy who had vitrectomy with silicone oil tamponade and the third group were 30 patients with diabetic retinopathy who underwent vitrectomy and tamponade with silicone oil. The intraocular pressure was measured and gonioscopy was performed in all patients one month before and after vitrectomy. The results showed that there is no statistically significant difference among IOP values before and after vitrectomy in the control group (p = 0.104) as well as in the preoperative IOP values among all three groups of patients. The data analysis determined that in both groups of patients with silicone oil tamponade after vitrectomy, there is a statistically significant difference in IOP values one month after the surgical procedure (p = 0.000). The mean IOP values in those patients a month after vitrectomy were significantly higher compared to the control group (p < 0.05). Comparison of the IOP one month after vitrectomy between the patients with retinal detachment and those with diabetic retinopathy showed no statistically significant difference (p = 0.331) but the qualitative analysis showed that the IOP one month after vitrectomy was 2 mmHg higher in the diabetic retinopathy group. The results suggest that there is no difference in angle width before and after vitrectomy among different groups of patients. Emulsified silicone oil was confirmed in 18% of patients in the retinal detachment group. In 17% of patients in the diabetic retinopathy group the emulsified oil was found in the angle, whereas a 10% of patients had neovascularization of the angle one month after vitrectomy. The IOP elevation in the early postoperative course may be caused by intravitreal instillation of the silicone oil after vitrectomy. Emulsification of the silicone oil may lead to the early IOP rise; especially in the diabetic patients with angle neovascularization which itself can additionally accelerate the development of the secondary glaucoma.