Optical coherence tomography angiography parameters in patients taking hydroxychloroquine therapy.

Purpose: The aim of this study is to measure retinal vessel density and flow rate area by optical coherence tomography angiography (OCTA) in patients with autoimmune diseases taking hydroxychloroquine (HCQ). Methods: The cross-sectional study included 98 patients divided into three groups. Group I included patients with the diagnosis of an autoimmune disease, for whom the introduction of HCQ was planned. Group II implied low-risk patients for retinal toxicity (≤5 years of HCQ use), whereas Group III implied patients that were at high-risk (>5 years of drug use). All patients underwent a computerized visual field, central macular thickness by optical coherence tomography, and OCTA measurements. Results: The vascular density was found to be statistically significantly decreased in the high-risk group compared to the control group in the superficial parafoveal zone (P = 0.030), whereas it was decreased compared to the low-risk and control groups in the deep layers whole (P = 0.006, P = 0.010, respectively) and perifoveal zones (P = 0.003, P = 0.010, respectively). The foveal avascular zone was significantly enlarged in the high-risk group compared to the control (P < 0.018). Retinal flow rates did not show statistically significant differences between the groups (P > 0.05). Conclusion: Patients treated with HCQ for more than 5 appear have a significant loss of vascular density in the parafoveal and perifoveal regions, and FAZ area is significantly increased compared to low-risk patients and controls. These findings indicate that OCTA may be beneficial for monitoring high-risk patients and may stratify their risk of further retinal damage.

Evaluation of dry eye symptoms and risk factors among medical students in Serbia.

BACKGROUND: Dry eye is a multifactorial disease defined less than 30 years ago. It is a relatively common disorder, affected by a number of well-known risk factors. Dry eye can be challenging to diagnose because of the possible discrepancy between patients' symptoms and clinical signs, and its overlap with other ocular surface diseases. Literature-wise, dry eye is usually associated with age and therefore investigated within older populations. Recently, studies focusing on young adult and student populations have demonstrated a higher prevalence of dry eye than previously expected. AIM: The study aims to determine the frequency of dry eye symptoms in the student population, and the impact of students' activities and habits as potential risk factors. METHODOLOGY: Our study involved 397 students from the medical school at the University of Belgrade, Serbia. Students were asked to complete an online survey that addressed general information, health, habits, and routine in everyday use of electronic devices. In addition, students completed a standard Ocular Surface Disease Index questionnaire. RESULTS: The prevalence of dry eye was 60.5% (240/397) in our study population. Contact lens wear (p<0.001), allergies (p = 0.049) and increased number of hours per day using VD devices for studying purposes (p = 0.014) were associtated with a higher risk of dry eye disease. Risk factors that did not significantly impact dry eye were the use of oral contraceptives, smoking, systemic diseases, year of study and sex. CONCLUSION: In our study, the prevalence of dry eye disease was similar or slightly higher than in previous studies among young adults. In addition, contact lenses, allergies and visual display devices were associated with the development of the dry eye.

Is there a potential link between keratoconus and autism spectrum disorders?: A case report and literature review.

RATIONALE: Eye rubbing (ER) is a proven factor that can trigger the onset and progression of keratoconus (KC). Apart from allergy, ER is a repetitive motor stereotypy. Eye rubbing is frequently observed in children with autism spectrum disorders (ASDs) and in individuals who may be at risk for developing KC. We present a child with ASD who developed progressive KC following standard corneal cross-linking (CXL), most likely because of abnormal ER associated with allergy and repetitive behavior due to ASD symptoms. PATIENT CONCERNS: A 14-year-old boy was referred to our clinic because of asymmetric visual acuity reduction. DIAGNOSIS: The child was diagnosed as having keratoconus. He had a strong ER habit. The child had been previously diagnosed as having ASD. INTERVENTIONS: Corneal cross-linking was performed in both the eyes. On account of keratoconus progression, most likely associated with persistent ER habit, he was retreated with CXL in the right eye. Behavioral modification intervention for ER habit reversal was also applied. OUTCOMES: Corneal cross-linking in combination with behavioral modification intervention for ER habit reversal prevented further KC progression. LESSONS: Behavioral interventions are likely to provide positive results in an ER habit reversal in children with ASD. Keratoconus treatment with CXL combined with behavioral management for ER reversal seemed effective in halting keratoconus progression in a young patient with ASD.

Disease activity and damage in patients with primary Sjogren's syndrome: Prognostic value of salivary gland ultrasonography.

OBJECTIVES: To assess the association between salivary ultrasonography (sUS) findings and disease activity and damage in patients with primary Sjogren's syndrome (pSS). We investigated the potential prognostic role of sUS as a tool in the assessment of disease activity. METHODS: In 303 pSS patients, disease activity was assessed by the European League Against Rheumatism (EULAR) Sjogren's Syndrome Disease Activity Index (ESSDAI), the EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI), the Sjogren's Syndrome Disease Activity Index (SSDAI) and the Sjogren's Syndrome Disease Damage Index (SSDDI). The sUS parenchymal inhomogeneity (de Vita scoring system) was assessed in 303 pSS patients and 111 heathy controls. A receiver operating characteristic (ROC) curve was used to determine the cut-off value of the pathological sUS score. Logistic regression analysis was performed to assess risk factors for moderate and high disease activity. RESULTS: A pathological sUS score ≥ 2 was recorded in 271 (89.7%) patients and 8 (8.6%) healthy controls. Patients with moderate and high ESSDAI and SSDAI scores had significantly higher US activity in comparison to that of pSS patients with low disease activity (p = 0.006; p = 0.01, respectively). Additionally, pSS patients with moderate and high SSDDI scores had higher US activity (p = 0.031). Pathological sUS correlated with the glandular domain within the ESSDAI and SSDDI (p<0.001). The patients with a severe US score (5-6) had a 3.5 times greater chance of having moderate or high disease activity. The specificity of the severe de Vita sUS score for ESSDAI and SSDAI was 85.1% and 85.2%, respectively. In contrast, the sensitivity of a severe de Vita sUS score for ESSDAI was low, at 29.2%, while the sensitivity for the SSDAI was higher, 42.3%. In the analysis of disease activity, a de Vita score ≥ 5 could be used as a risk factor for moderate and high ESSDAI (p = 0.042) and SSDAI (p = 0.006). CONCLUSIONS: Pathological salivary gland ultrasonography is associated with high disease activity and damage in pSS. Consequently, sUS abnormalities might be surrogate items for glandular domains in the assessment of disease activity and damage. Thus, ultrasonography of the salivary gland combined with clinical and serological markers might be part of the next prognostic and therapeutic algorithm in the near future.

Human external ophthalmomyiasis caused by Lucilia sericata Meigen (Diptera: Calliphoridae)--a green bottle fly.

Ophthalmomyiasis externa is the result of infestation of the conjunctiva by the larval form or maggots of flies from the order Diptera. If not recognized and managed appropriately, it can be complicated by the potentially fatal condition ophthalmomyiasis interna. Ophthalmomyiasis externa is mainly caused by the sheep bot fly (Oestrus ovis). We present the first case, to our knowledge, of ophthalmomyiasis externa in an elderly woman from Belgrade caused by Lucilia sericata Meigen--a green bottle fly.

Control of TNF-induced dendritic cell maturation by hybrid-type N-glycans.

The activity of α-1,2-mannosidase I is required for the conversion of high-mannose to hybrid-type (ConA reactive) and complex-type N-glycans (Phaseolus vulgaris-leukoagglutinin [PHA-L] reactive) during posttranslational protein N-glycosylation. We recently demonstrated that α-1,2-mannosidase I mRNA decreases in graft-infiltrating CD11c(+) dendritic cells (DCs) prior to allograft rejection. Although highly expressed in immature DCs, little is known about its role in DC functions. In this study, analysis of surface complex-type N-glycan expression by lectin staining revealed the existence of PHA-L(low) and PHA-L(high) subpopulations in murine splenic conventional DCs, as well as in bone marrow-derived DC (BMDCs), whereas plasmacytoid DCs are nearly exclusively PHA-L(high). Interestingly, all PHA-L(high) DCs displayed a strongly reduced responsiveness to TNF-α-induced p38-MAPK activation compared with PHA-L(low) DCs, indicating differences in PHA-L-binding capacities between DCs with different inflammatory properties. However, p38 phosphorylation levels were increased in BMDCs overexpressing α-1,2-mannosidase I mRNA. Moreover, hybrid-type, but not complex-type, N-glycans are required for TNF-α-induced p38-MAPK activation and subsequent phenotypic maturation of BMDCs (MHC-II, CD86, CCR7 upregulation). α-1,2-mannosidase I inhibitor-treated DCs displayed diminished transendothelial migration in response to CCL19, homing to regional lymph nodes, and priming of IFN-γ-producing T cells in vivo. In contrast, the activity of α-1,2-mannosidase I is dispensable for LPS-induced signaling, as well as the DCs' general capability for phenotypic and functional maturation. Systemic application of an α-1,2-mannosidase I inhibitor was able to significantly prolong allograft survival in a murine high-responder corneal transplantation model, further highlighting the importance of N-glycan processing by α-1,2-mannosidase I for alloantigen presentation and T cell priming.

Influence of combined treatment of low dose rapamycin and cyclosporin A on corneal allograft survival.

PURPOSE: To analyze the immune modulatory effect of low-dose systemic treatment with rapamycin (Rapa) alone or in combination with cyclosporin A (CsA) in a high-responder corneal allograft model. METHODS: A total of 80 C57BL/6 mice received corneal grafts from BALB/c donors. Recipients were treated with either CsA 3 mg/kg/day or Rapa 0.5 mg/kg/day monotherapy or received combined treatment. Immunomodulatory treatment was started on the day of surgery, and continued for 14 days. The frequency of CD4(+)CD25(+)Foxp3(+) T regulatory cells (Treg) in secondary lymphoid organs was measured by flow cytometry. Development of IFN-gamma producing alloreactive T cells was estimated by Elispot. In addition, corneal samples were subjected to real-time RT-PCR analysis for cytokine transcription. RESULTS: Monotherapy with Rapa significantly delayed allograft rejection (13.4 +/- 1.34 days, p = 0.03). However, the combination of both, low-dose Rapa and CsA prolonged corneal allograft survival at a significantly higher level (MST = 17.1 +/- 1.37 days, p = 0.0001) than in the control group (MST = 11.2 +/- 1.91 days). Rapa monotherapy increased the frequency of CD4(+)CD25(+)Foxp3(+)Treg in draining lymph nodes, whereas addition of CsA reduced Tregs. Monotherapy with Rapa as well as combined treatment prevented development of IFN-gamma producing alloreactive T cells in spleen. Combined treatment resulted in down-regulation of intragraft CD3, IL-2, IFN-gamma and IL-10 transcription (p = 0.028, p = 0.027, p = 0.028 and p = 0.027 respectively). CONCLUSIONS: Combined treatment with low-dose CsA and Rapa resulted in superior graft survival, and effectively modulated mRNA expression of inflammation and infiltration markers.