Nenad Petrovic

Purpose: The purpose of this study was to characterize the distribution and longitudinal evolution of intraretinal and subretinal hyperreflective foci (HF) in treatment-naive neovascular age-related macular degeneration (nAMD), and to examine associations between HF burden, hyperreflective material boundary remodeling (HRM-BR), and best-corrected visual acuity (BCVA) outcomes following bevacizumab treat-and-extend therapy. Methods: This was a retrospective observational study of 84 treatment-naive nAMD eyes receiving intravitreal bevacizumab via a treat-and-extend protocol. Spectral-domain OCT (Revo FC, Optopol) was performed at baseline (M0), month 3 (M3), and month 6 (M6). HF were quantified in the intraretinal and subretinal compartments using ImageJ software (version 1.54, National Institutes of Health, Bethesda, MD, USA) by two masked graders, with inter-rater agreement assessed by intraclass correlation coefficient (ICC). Eyes were classified into four HRM evolution patterns following the framework of Yu et al. Primary outcome was BCVA change from M0 to M6. Multivariable linear regression was performed to assess independent predictors of BCVA change. Results: Baseline intraretinal HF counts increased significantly across HRM Patterns 1 through 4 (median 0, 6, 4, and 8, respectively; Kruskal–Wallis p < 0.001; 95% CI for Spearman r = 0.471: [0.286, 0.623]). A higher baseline intraretinal HF count correlated with worse BCVA change at M6 (r = −0.300, 95% CI [−0.483, −0.092], p_adj = 0.010). In the primary multivariable model (n = 67), both intraretinal HF burden (β = −0.449, 95% CI [−0.879, −0.020], p = 0.041) and HRM width (β = −0.003, 95% CI [−0.005, −0.001], p = 0.014) were independent predictors of BCVA change. The transient M3 intraretinal HF peak in Pattern 3 eyes (median 4 → 12 → 4) was statistically confirmed by Wilcoxon signed-rank testing (M0 → M3: p = 0.004; M3 → M6: p = 0.001). Conclusions: Intraretinal HF burden is a graded marker of HRM pattern severity and an independent predictor of visual outcomes in nAMD, alongside HRM width. The statistically validated transient M3 HF peak in Pattern 3 may represent an early OCT signal of active boundary remodeling.

Background and Objectives: Is it possible to predict the course of disease in patients with pseudoexfoliation based on blood examination? Materials and Methods: This retrospective study included 800 patients recruited for cataract surgery in the Clinic of Ophthalmology, University Clinical Centre Kragujevac, Serbia. The patients were divided into four groups: pseudoexfoliation syndrome early stage group (n = 200 patients), pseudoexfoliation syndrome late stage group (n = 200 patients), pseudoexfoliation glaucoma group (n = 200 patients) and the control group (n = 200 patients). During the preoperative process, some blood examination must be performed. We retrospectively used the results for the blood cell counts that we obtained from the patients. We recorded the neutrophil, lymphocyte, platelet, monocyte and leucocyte numbers, as well as the lipid profile, and simply calculated the ratio of their values, which we considered through different stages of the disease. Results: Our results indicated that there were no significant differences between all the groups examined in terms of leucocyte, neutrophil and lymphocyte count, but we recorded significant differences in the monocyte and platelet count. It was interesting that the monocyte count increased in the late stage of pseudoexfoliation syndrome and pseudoexfoliation glaucoma, in comparison with the control group and patients with early stage pseudoexfoliation syndrome. The lipid profile analysis indicated only increased values of LDL in patients with pseudoexfoliation (syndrome/glaucoma) in comparison with the control group. Conclusions: Monocytes are the main source of various cytokines, so our results support the proinflammatory theory of pseudoexfoliation development. Monocytes are the main cells in chronic inflammation, which leads to pseudoexfoliation syndrome. Platelets play an important role in the differentiation and activation of monocytes, as well as in the process of chronic inflammation and fibrosis, which are significant for pseudoexfoliation material production. A disturbed lipid profile in patients with pseudoexfoliation is expected, as they are at higher risk for cardiovascular and cerebrovascular diseases.

Introduction/Objective. Cataract represents a blur of the crystalline lens. The only possible way of cataract treatment is the surgical one. One of the most common postoperative complications is the development of posterior capsule opacification (PCO). The aim of this study was to exam the effect of three different acrylic intraocular lenses (IOLs) and the capsulorhexis diameter on PCO development. Methods. The study included 92 patients with a diagnosis of senile cataract divided into three groups according to the IOL type. Every group was further divided into two subgroups depending on capsulorhexis size. PCO was measured in the first, sixth, 12th, 18th, and 24th month after the phacoemulsification. Results. The lowest PCO 24 months after phacoemulsification was measured in patients with three-piece hydrophobic IOL (0.3 ? 0.08). Capsulorhexis diameter less than 5 mm had a statistically significant effect in patients with single-piece hydrophilic (0.416 ? 0.187) and single-piece hydrophobic IOL (0.411 ? 0.082) for two years follow-up. Conclusion. PCO causes a decrease of visual acuity and can be a reason for patients? dissatisfaction in postoperative period. The only possible way for the treatment of developed PCO is the usage of YAG laser capsulotomy, a procedure which can be associated with serious complications. Thereby, the finest way for PCO treatment is its prevention. The main role in that prevention has a choice of adequate surgical technique and IOL.

Background/Aim. One of the postoperative complications of phacoemulsification is the formation of fluid-filled microvacuoles inside the implanted intraocular lens (IOL). This condition is known as ?glistening?. The aim of this study was to determine the incidence of glistening formation after the implantation of three different acrylic IOLs during the two-year follow-up period. Methods. Cataract surgery was performed in 93 patients (93 eyes) with developed senile cataracts. According to the implanted IOL, patients were equally divided into three groups: group with single-piece hydrophilic (SPHphil) acrylic IOL, group with single-piece hydrophobic (SPHphob) acrylic IOL, and group with three-piece hydrophobic (TPHphob) acrylic IOL. The presence of glistening was measured five times: 1, 6, 12, 18, and 24 months after phacoemulsification. Results. Statistically significantly lower glistening incidence was recorded in the SPHphil group compared to the SPHphob and TPHphob group, six months after phacoemulsification (p < 0.05). That difference was even higher one year after the cataract surgery (p < 0.01) and remained at that level until the end of the study. During the whole follow-up period, no statistically significant difference was recorded among SPHphob and TPHphob groups (p > 0.05). Conclusion. The presence of glistening was recorded in all groups. Our results strongly suggest that the progression of glistening was the most pronounced in the first postoperative year. However, a very low glistening incidence associated with SPHphil IOL could be particularly beneficial in patients expected to develop increased postoperative inflammation.

BACKGROUND: The biological properties of silicone elastomers such as polydimethylsiloxane (PDMS) have widespread use in biomedicine for soft tissue implants, contact lenses, soft robots, and many other small medical devices, due to its exceptional biocompatibility. Additive manufacturing of soft materials still has significant challenges even with major advancements that have occurred in development of these technologies for customized medical devices and tissue engineering. OBJECTIVE: The aim of this study was to develop a mathematical model of tangential stress in relation to shear stress, shear rate, 3D printing pressure and velocity, for non-Newtonian gels and fluids that are used as materials for 3D printing. METHOD: This study used FENE (finitely extensible nonlinear elastic model) model, for non-Newtonian gels and fluids to define the dependences between tangential stress, velocity, and pressure, considering viscosity, shear stress and shear rates as governing factors in soft materials friction and adhesion. Experimental samples were fabricated as showcases, by SLA and FDM 3D printing technologies: elastic polymer samples with properties resembling elastic properties of PDMS and thermoplastic polyurethane (TPU) samples. Experimental 3D printing parameters were used in the developed analytical solution to analyse the relationships between governing influential factors (tangential stress, printing pressure, printing speed, shear rate and friction coefficient). Maple software was used for numerical modelling. RESULTS: Analytical model applied on a printed elastic polymer, at low shear rates, exhibited numerical values of tangential stress of 0.208–0.216 N m - 2 at printing velocities of 0.9 to 1.2 mm s - 1, while the coefficient of friction was as low as 0.09–0.16. These values were in accordance with experimental data in literature. Printing pressure did not significantly influence tangential stress, whereas it was slightly influenced by shear rate changes. Friction coefficient linearly increased with tangential stress. CONCLUSION: Simple analytical model of friction for elastic polymer in SLA 3D printing showed good correspondence with experimental literature data for low shear rates, thus indicating possibility to use it for prediction of printing parameters towards desired dimensional accuracy of printed objects. Further development of this analytical model should enable other shear rate regimes, as well as additional soft materials and printing parameters.

This paper reviews the latest trends and applications of silicone in ophthalmology, especially related to intraocular lenses (IOLs). Silicone, or siloxane elastomer, as a synthetic polymer, has excellent biocompatibility, high chemical inertness, and hydrophobicity, enabling wide biomedical applications. The physicochemical properties of silicone are reviewed. A review of methods for mechanical and in vivo characterization of IOLs is presented as a prospective research area, since there are only a few available technologies, even though these properties are vital to ensure medical safety and suitability for clinical use, especially if long-term function is considered. IOLs represent permanent implants to replace the natural lens or for correcting vision, with the first commercial foldable lens made of silicone. Biological aspects of posterior capsular opacification have been reviewed, including the effects of the implanted silicone IOL. However, certain issues with silicone IOLs are still challenging and some conditions can prevent its application in all patients. The latest trends in nanotechnology solutions have been reviewed. Surface modifications of silicone IOLs are an efficient approach to further improve biocompatibility or to enable drug-eluting function. Different surface modifications, including coatings, can provide long-term treatments for various medical conditions or medical diagnoses through the incorporation of sensory functions. It is essential that IOL optical characteristics remain unchanged in case of drug incorporation and the application of nanoparticles can enable it. However, clinical trials related to these advanced technologies are still missing, thus preventing their clinical applications at this moment.

Introduction/Objective. Pseudoexfoliation (PEX) is an age-related systemic disorder, which can affect the whole body, as well as the eye. It is characterized by abnormal production and accumulation of pseudoexfoliative material. When present in the eye, it can cause different difficulties, but most common are PEX glaucoma (XFG) and intraoperative and postoperative complications of cataract surgeries. The aim of this study was to determine an incidence of patients with PEX in two different regions of Serbia. Methods. The study included 7451 patients scheduled for cataract surgery in two regions of Serbia. It was designed as a multicentric, retrospective study with evaluation of the medical records of all patients who underwent cataract surgery. The study evaluated: incidence of PEX syndrome and PEX glaucoma, age, and sex of patients, as well as preoperative antiglaucomatous therapy and intraoperative and postoperative cataract surgery complications. Results. PEX syndrome (XFS)was recorded in 676 patients (407 females and 269 males), while 243 patients had XFS. It represented 3.26% of patients included in the study. Mean age of XFG patients was 78.1 ?} 2.1 years with a statistically significant difference (p < 0.05) among incidence of XFG in females compared to males. Intraoperative and postoperative complications during cataract surgery were significantly common in patients with PEX (p < 0.05) Conclusion. PEX can complicate cataract surgery, while on the other hand XFG is more difficult to treat and control than most other glaucomas. Therefore, patients with PEX require special treatment during follow-up and treatment.

Background and Objectives: The main cause of the vision loss in diabetics is the development of diabetic macular edema, regardless of the stage of diabetic retinopathy. The paper aimed to examine whether the additional intravitreal application of triamcinolone acetonide to continuous anti-vascular endothelial growth factor therapy could improve therapeutic outcomes for pseudophakic eyes with persistent diabetic macular edema. Materials and Methods: twenty-four pseudophakic eyes with refractory diabetic macular edema, that had appeared despite three previously administered intravitreal injections of aflibercept, were divided into two groups (twelve eyes in each group). The first group continued to have aflibercept administered according to a fixed dosing regimen (once in two months). Triamcinolone acetonide 10 mg/0.1 mL (administered once per four months) was included for the second group, i.e., their treatment continued with a combination of aflibercept + triamcinolone acetonide. Results: The reduction in central macular thickness was higher in the eyes treated with combined therapy (aflibercept + triamcinolone acetonide) compared with the use of aflibercept alone during the entire 12-month follow-up period (3rd month p = 0.019; 6th month p = 0.023; 9th month p = 0.027; 12th month p = 0.031). As was evident from the p-values, the differences were statistically significant. No statistically significant difference was recorded for visual acuity: 3rd month p = 0.423; 6th month p = 0.392; 9th month p = 0.413; 12th month p = 0.418. Conclusions: Combined anti-vascular endothelial growth factor and steroid therapy leads to a better anatomical outcome of persistent diabetic macular edema in pseudophakic eyes, but does not lead to a more significant improvement in visual acuity than continuous anti-VEGF therapy alone.

Introduction/Objective. Diabetic macular oedema is the accumulation of fluid in the macular tissue leading to its thickening. The aim of the study was to evaluate the efficacy of concentrated triamcinolone acetonide 10 mg / 0.1 ml injection into the suprachoroidal space in patients with diabetic macular oedema and decreased visual acuity. Methods. In 12 eyes with diabetic macular oedema, without any prior treatment, using a small-diameter 26G needle, an injection of 10 mg / 0.1 ml triamcinolone acetonide was applied into the suprachoroidal space in the superotemporal quadrant of the eye 4 mm from the limbus. Prior to the injection, as well as one, three, six, nine, and 12 months after the injection, visual acuity and intraocular pressure were measured, and central subfield thickness was recorded using optical coherence tomography. Results. After one, three, six, and nine post-injection months there was a statistically significant reduction in central subfield thickness (315.92 ?m, 257.66 ?m, 281.08 ?m and 295.51 ?m, respectively) compared to the baseline of 447.67 ?m. At the end of the 12th month an increase in central subfield thickness was observed again (392.16 ?m). Visual acuity improved significantly from the baseline (0.32) during the first three months (0.61) and remained stable until the end of the nineth month (0.51), but at the end of 12 months it decreased again (0.39). No significant intraocular pressure elevation and cataract development were observed in either eye during the entire follow-up period. Conclusion. A single dose of 10 mg / 0.1 ml triamcinolone acetonide injected in suprachoroidal space can significantly stabilize diabetic macular oedema and maintain satisfactory visual acuity for up to nine months.

Background/Aim. Since glaucoma has a very high prevalence worldwide, it is important to examine additional treatment modalities, especially the prevention of its progression. The aim of the study was to determine the importance of laser peripheral iridotomy (LPI) in patients with acute primary angle closure (APAC) in preventing primary angle closure glaucoma progression and APAC in the fellow eye. Methods. The research included 40 patients and 80 eyes treated between 2017 and 2021, which was also the follow-up period in the study. In all patients, LPI was performed bilaterally on both the APAC-affected eye and the healthy fellow eye. The patients with an age range from 40 to 79 years who had the pupillary block in one eye were monitored. All patients underwent bilateral LPI, and the changes in angle width were monitored using gonioscopy. Intraocular pressure (IOP) measurements were made with an applanation tonometer and Vertical Cup/Disc ratio (Ver C/D rat) performing biomicroscopic examination with indirect ophthalmoscopy and +90 D lens. Results. All 40 patients underwent bilateral LPI. The angle width of the APAC-affected eye before treatment was 0.15 ? 0.36, and 1.20 ? 0.41 of the fellow eye. After 12 months, the measurements taken were 0.85 ? 0.36 for the affected eye and 1.90 ? 0.36 for the fellow eye (Wilcoxon rank test, p < 0.01 statistically significant difference). The mean value of IOP in the eye without progression of the disease before therapy was 53.6 ? 3.73 mmHg, while in the eye with progression, it was 60.10 ? 4.37 mmHg. After 12 months, it was 14.92 ? 1.22 mmHg in the eye without progression, while in the eye with disease progression, it was 23.40 ? 2.53 mmHg (independent samples t-test, p < 0.01). The change in the Ver C/D rat in the eye without progression was 0.40 ? 0.10, while in the eye with progression, it was 0.45 ? 0.05. After 12 months, it remained unchanged in the eye without progression, while in the eye with progression, it was 0.65 ? 0.06 (independent samples t-test, p < 0.01). Conclusion. Simultaneous LPI has been proven efficient in patients with APAC in both affected and fellow eyes.