Cataract Surgery in nAMD Patients Receiving Intravitreal Aflibercept Injections.

Background: To evaluate functional and anatomical outcomesof cataract surgery in neovascular age-related macular neovascularization (nAMD) eyes receiving anti-vascular endothelial growth factor (anti-VEGF) intravitreal injections in modified pro re nata (PRN) regimen. Materials and Methods: Sixty eyes of 60 nAMD patients, including 41 women (68.3%) and 19 men (31.7%) in an average age of 77.35 ± 6.41 years, under treatment with intravitreal aflibercept injections in modified PRN regimen with no signs of macular neovascularization (MNV) activity during two consecutive visits were included in this prospective, observational study. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), as well as the number of anti-VEGF injections were monitored six months before and after phacoemulsification with intraocular lens (IOL) implantation. Further, the change of the abovementioned parameters was assessed during the six-month follow-up period for CRT and the number of injections, while the BCVA was monitored for 54 months. Results: BCVA measured on the first day after surgery (0.17 ± 0.19 logMAR) as well as in the six-month post-surgery (0.13 ± 0.16 logMAR) significantly improved compared to preop values (0.42 ± 0.20 logMAR). BCVA remains stable during the observational period. We found that both differences were statistically significant (p < 0.01). The mean CRT and the mean number of injections did not differ between the six-month pre- and post-surgical periods. Conclusions: We showed the beneficial effect of phacoemulsification in nAMD patients treated with anti-VEGF agents on visual outcomes in the short and long term. Cataract surgery in nAMD eyes treated with anti-VEGF injections does not increase the frequency of anti-VEGF injections and does not cause deterioration of the macular status.

Ocular Changes in Cystic Fibrosis: A Review.

Cystic fibrosis (CF), also known as mucoviscidosis, is the most common autosomal recessive genetic disease in the Caucasian population, with an estimated frequency of 1:2000-3000 live births. CF results from the mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene localized in the long arm of chromosome 7. The product of CFTR gene expression is CFTR protein, an adenosine triphosphate (ATP)-binding cassette (ABC) transporter that regulates the transport of chloride ions (Cl-) across the apical cell membrane. Primary manifestations of CF include chronic lung and pancreas function impairment secondary to the production of thick, sticky mucus resulting from dehydrated secretions. It is well known that CF can cause both anterior and posterior ocular abnormalities. Conjunctival and corneal xerosis and dry eye disease symptoms are the most characteristic manifestations in the anterior segment. In contrast, the most typical anatomical and functional changes relating to the posterior segment of the eye include defects in the retinal nerve fiber layer (RNFL), vascular abnormalities, and visual disturbances, such as reduced contrast sensitivity and abnormal dark adaptation. However, the complete background of ophthalmic manifestations in the course of CF has yet to be discovered. This review summarizes the current knowledge regarding ocular changes in cystic fibrosis.

Swept-source OCT for corneal graft quantitative evaluation in the eye bank and the correlation of the measurements to pre-excision values.

Quantitative evaluation of the human corneal grafts stored in the tissue banks is usually limited to endothelial cell density and central thickness. Swept-source OCT (SS-OCT) is capable of measuring the central curvatures of the corneal tissue prepared for transplantation without loss of sterileness, providing insights on its refractive state. The aim of the paper is to compare in vitro SS-OCT measurements with pre-excision values. Hand-held keratometry and ultrasound pachymetry was performed on 22 corneas before excision of corneoscleral button and insertion in the vial with Eusol-C solution (AlchimiaS.r.l, Nicolò, Italy). After 12 to 36 h of hypothermic storage the corneas were examined within the vials with custom built SS-OCT system maintaining a sterile environment. The anterior and posterior central curvatures, and central corneal thickness (CCT) were measured. Rotation of the corneoscleral button was controlled by making a 6-o'clock mark during excision. Mean pre-excision CCT was 626.45 ± 28.71 µm and 468.05 ± 52.96 µm when measured with SS OCT (r = 0.55; p < 0.001). Respective values for average keratometry were 7.74 ± 0.39 mm and 7.92 ± 0.57 mm (r = 0.6; p = 0.22). Although high differences were observed in corneal thickness, keratometric radius of curvature at the flat (r = 0.42; p < 0.001) and steep (r = 0.62; p = 0.014) meridian of the anterior corneal surface, as well as corneal anterior astigmatism (r = 0.3; p < 0.001), showed good correlation with pre-excision values. SS-OCT is capable of providing quantitative evaluation of the human corneal grafts in hypothermic storage. Good correlation between curvature measurements before excision and during banking in the vial indicates its clinical utility.

Aflibercept versus Faricimab in the Treatment of Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema: A Review.

Diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD) are common retinal vascular diseases responsible for most blindness in the working-age and older population in developed countries. Currently, anti-VEGF agents that block VEGF family ligands, including ranibizumab, bevacizumab (off-label use), brolucizumab, and aflibercept, are the first-line treatment for nAMD and DME. However, due to the complex pathophysiological background of nAMD and DME, non-response, resistance during anti-VEGF therapy, and relapses of the disease are still observed. Moreover, frequent injections are a psychological and economic burden for patients, leading to inadequate adhesion to therapy and a higher risk of complications. Therefore, therapeutic methods are strongly needed to develop and improve, allowing for more satisfactory disease management and lower treatment burden. Currently, the Ang/Tie-2 pathway is a promising therapeutic target for retinal vascular diseases. Faricimab is the first bispecific monoclonal antibody for intravitreal use that can neutralize VEGF and Ang-2. Due to the prolonged activity, faricimab allows extending the interval between successive injections up to three or four months in nAMD and DME patients, which can be a significant benefit for patients and an alternative to implanted drug delivery systems.

Methanol-induced optic neuropathy: a still-present problem.

Methanol-induced optic neuropathy (Me-ION) is a serious condition that may result in long-term or irreversible visual impairment or even blindness secondary to damage and loss of function of the optic nerve and retina. Me-ION shows a tendency to occur as mass poisonings around the world with a clear predilection for poor societies in developing countries. The main mechanism underlying the molecular basis of Me-ION is the inhibition of the mitochondrial oxidative phosphorylation process through the binding of the toxic metabolite of methanol-formic acid-with the key enzyme of this process-cytochrome c oxidase. However, other mechanisms, including damage to the eye tissues by oxidative stress causing the intensification of the oxidative peroxidation process with the formation of cytotoxic compounds, as well as an increase in the synthesis of pro-inflammatory cytokines and influence on the expression of key proteins responsible for maintaining cell homeostasis, also play an important role in the pathogenesis of Me-ION. Histopathological changes in the eye tissues are mainly manifested as the degeneration of axons and glial cells of the optic nerve, often with accompanying damage of the retina that may involve all its layers. Despite the development of therapeutic approaches, persistent visual sequelae are seen in 30-40% of survivors. Thus, Me-ION continues to be an important problem for healthcare systems worldwide.

Examination of Inner Retinal Layers in Unilateral Wet Age-Related Macular Degeneration Treated with Anti-VEGF, Compared to Fellow Untreated Eyes.

The main aim of this study was to characterize the retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) thickness in the macular area eyes affected by wet age-related macular degeneration (wAMD) treated with anti-VEGF and compare the results with the control of fellow untreated eyes affected by early stages of dry age-related macular degeneration (dAMD). Additionally, we aimed to estimate if the number of injections received and other factors, including age, best-corrected visual acuity (BCVA), or sex, may affect the differences in the obtained measurements of retinal nerve fiber layer thickness. We prospectively included 106 eyes of 53 patients with unilateral wet age-related macular degeneration. The fellow eyes with non-advanced dry age-related macular degeneration served as a control group in a cross-sectional study. RNFL and GCL in the macular region were evaluated using optical coherence tomography, with outcomes expressed as differences in the thickness of both examined layers between the study and control groups. We found thinner GCL in wAMD vs. dAMD (p < 0.001). In turn, the RNFL layer did not show any statistically significant differences between the two groups (p = 0.409). Similarly, we found a statistically significant correlation between the number of injections and the layer thickness (p = 0.106). Among all assessed parameters, age over 73 was the only factor significantly affecting the thickness of the retinal nerve fiber layer in both groups (p = 0.042). The morphology of the inner layers of the retina in dry and wet AMD seems to differ, possibly due to differences in the etiopathogenesis of these two forms of the disease. In our study, the retinal ganglion cell layer was thinner in the treated vs. fellow eye (with dry AMD), while the nerve fiber layer was not significantly different between the groups. The number of anti-VEGF injections had no effect on the thickness of the macular nerve fiber layer.

Evaluation of Blood Coagulation Parameters and ADMA, NO, IL-6, and IL-18 Serum Levels in Patients with Neovascular AMD before, during, and after the Initial Loading Phase of Intravitreal Aflibercept.

We evaluated the effect of intravitreal injections of aflibercept (IVA) on blood coagulation parameters including prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT), as well as asymmetric dimethylarginine (ADMA), nitric oxide (NO), interleukin 6 (IL-6), and interleukin 18 (IL-18) serum levels in patients with neovascular AMD (nAMD). Twenty-two eyes of 22 patients with nAMD were included. Parameters were evaluated before and 2-3 days after the first IVA injection, and then immediately before and 2-3 days after the third IVA injection. We revealed prolongation of the TT after the initial loading phase of IVA (p = 0.041) and a significant increase in IL-18 serum concentration immediately before the third IVA administration compared to baseline (p = 0.037). There were no statistically significant differences of other parameters and PT, APTT, ADMA, NO, and IL-6 values remained within the normal range at each of the time points of the study. Our results suggest that repeated IVA administration may affect the common blood coagulation pathway, which manifests as a prolongation of the TT value. Furthermore, we showed a significant increase in serum concentration of the pro-inflammatory cytokineIL-18during the initial loading phase of IVA.

Association between serotonin-norepinephrine reuptake inhibitors and acute angle closure: What is known?

Serotonin-norepinephrine reuptake inhibitors are widely used antidepressants with a relatively safe profile. One of the complications associated with this group of drugs is acute angle closure. The mechanisms linking serotonin-norepinephrine reuptake inhibitors and acute angle closure are complex and may be interlinked with the effects of the drug on the inhibition of serotonin and noradrenaline reuptake, as well as pseudo-anticholinergic effects, dopaminergic effects, and idiosyncratic reactions with the drug molecule in the eye. Individual characteristics, such as polymorphisms of the gene encoding the 2D6 subunit of cytochrome P450, may affect the metabolism of the serotonin-norepinephrine reuptake inhibitor, whereas the combination with other drugs may lead to an increased risk of iridocorneal angle closure and may further exacerbate other mechanisms. Improved knowledge of the mechanisms linking serotonin-norepinephrine reuptake inhibitors and acute angle closure and of the risk factors predisposing to patients to acute angle closure will reduce the number of patients affected by this dangerous complication.

Systemic lupus erythematosus of the urinary tract: focus on lupus cystitis.

Systemic lupus erythematosus (SLE) frequently manifests as urinary tract disease, most commonly in the form of lupus nephritis. Bladder involvement in the disease course takes a subclinical form and may affect both children and adults. Lupus cystitis can precede SLE diagnosis and may present with very unspecific urinary and digestive tract symptoms or no symptoms at all. The exact mechanism of bladder inflammation in lupus is not fully understood; however, histopathological studies suggest a possible role of immune complex-mediated small vessel vasculitis. Lupus cystitis is a rare SLE manifestation, but poses a challenge for physicians, due to its complex diagnostics and treatment.