Local Energy Decomposition Analysis of London Dispersion Effects: From Simple Model Dimers to Complex Biomolecular Assemblies.

ConspectusLondon dispersion (LD) forces are ubiquitous in chemistry, playing a pivotal role in a wide range of chemical processes. For example, they influence the structure of molecular crystals, the selectivity of organocatalytic transformations, and the formation of biomolecular assemblies. Harnessing these forces for chemical applications requires consistent quantification of the LD energy across a broad and diverse spectrum of chemical scenarios. Despite the great progress made in recent years in the development of experimental strategies for LD quantification, quantum chemical methods remain one of the most useful tools in the hand of chemists for the study of these weak interactions. Unfortunately, the accurate quantification of LD effects in complex systems poses many challenges for electronic structure theories. One of the problems stems from the fact that LD forces originate from long-range electronic dynamic correlation, and hence, their rigorous description requires the use of complex, highly correlated wave function-based methods. These methods typically feature a steep scaling with the system size, limiting their applicability to small model systems. Another core challenge lies in disentangling short-range from long-range dynamic correlation, which from a rigorous quantum mechanical perspective is not possible.In this Account, we describe our research endeavors in the development of broadly applicable computational methods for LD quantification in molecular chemistry as well as challenging applications of these schemes in various domains of chemical research. Our strategy lies in the use of local correlation theories to reduce the computational cost associated with complex electronic structure methods while providing at the same time a simple means of decomposition of dynamic correlation into its long-range and short-range components. In particular, the local energy decomposition (LED) scheme at the domain-based local pair natural orbital coupled cluster (DLPNO-CCSD(T)) level has emerged as a powerful tool in our research, offering a clear-cut quantitative definition of the LD energy that remains valid across a plethora of different chemical scenarios. Typical applications of this scheme are examined, encompassing protein-ligand interactions and reactivity studies involving many fragments and complex electronic structures. In addition, our research also involves the development of novel cost-effective methodologies, which exploit the LED definition of the LD energy, for LD energy quantification that are, in principle, applicable to systems with thousands of atoms. The Hartree-Fock plus London Dispersion (HFLD) scheme, correcting the HF interaction energy using an approximate CCSD(T)-based LD energy, is a useful, parameter-free electronic structure method for the study of LD effects in systems with hundreds of molecular fragments. However, the usefulness of the LED scheme reaches beyond providing an interpretation of the calculated DLPNO-CCSD(T) or DLPNO-MP2 interaction energies. For example, the dispersion energies obtained from the LED can be fruitfully used in order to parametrize semiempirical dispersion models. We will demonstrate this in the context of an emerging semiempirical method, namely, the Natural Orbital Tied Constructed Hamiltonian (NOTCH) method. NOTCH incorporates LED-derived LD energies and shows promising accuracy at a minimum amount of empiricism. Thus, it holds substantial promise for large and complex systems.

Exploring the Limits of Intramolecular London Dispersion Stabilization with Bulky Dispersion Energy Donors in Alkane Solution.

We present an experimental study of a cyclooctatetraene-based molecular balance disubstituted with increasingly bulky tert-butyl (tBu), adamantyl (Ad), and diamantyl (Dia) substituents in the 1,4-/1,6-positions for which we determined the valence-bond shift equilibrium in n-hexane (hex), n-octane (oct), and n-dodecane (dod). Computations including implicit and explicit solvation support our temperature-dependent NMR equilibrium measurements indicating that the more sterically crowded 1,6-isomer is always favored, irrespective of solvent, and that the free energy is quite insensitive to substituent size.

GLP-1 agonist liraglutide improves ouabain-induced mania and depressive state via GSK-3ß pathway.

Bipolar disorder (BD) is a severe mental illness characterized by aberrant mood changes between hypomania and mania or mixed states and depression. Metabolic changes also accompany disease progression and cause significant morbidity. Symptomatic treatment options are available, but asymptomatic patients and poor drug responders are significant problems. Based on the most common pharmacological agent that is used in the treatment, lithium and its main mechanisms of action, oxidative stress, and glycogen synthase kinase-3ß (GSK-3ß) signaling are extensively investigated. However, knowledge about the effects of compounds that positively affect oxidative stress and GSK-3ß signaling, such as glucagon-like peptide-1 (GLP-1) mimetics, liraglutide, is still missing. Therefore, in this study, we aimed to investigate the effects of liraglutide on the ouabain-induced bipolar disease model in rats. After intracerebroventricular single dose ouabain administration, animals were treated with 100, 200, and 400 µg/kg liraglutide (s.c.) and valproic acid (200 mg/kg, i.p.) for 10 d. The locomotion and depressive states of animals were assessed by an open field, forced swimming test, and sucrose preference tests. Serum total antioxidant (TAS) and oxidant states (TOS) and glutathione, malonyl dialdehyde (MDA) levels in the brain tissue were determined. GSK-3ß phosphorylation was evaluated by western blotting. Our results demonstrated that liraglutide attenuated ouabain-induced hyperlocomotion and depressive state. Additionally, liraglutide prevented oxidative stress after ouabain administration. Decreased GSK-3ß phosphorylation due to the ouabain insult was alleviated by liraglutide treatment. These findings indicate that the manic and depressive-like behaviors are ameliorated by liraglutide, which exerted antioxidant action, possibly improving GSK-3ß phosphorylation.

Effects of acupuncture on pain and levels of IL-17 and IL-23 in the treatment of non-thermal endovenous ablation: A randomized clinical trial.

OBJECTIVES: Acupuncture is one of the oldest therapeutic interventions in the world for the treatment of pain, musculoskeletal diseases, and inflammation. This study aimed to investigate the effect of acupuncture on pain and IL-17 and IL-23 levels in the treatment of endovenous ablation. METHODS: The study was a randomized controlled trial. Patients were divided into group C (Control, n = 35) and group A (Acupuncture, n = 35). Group A patients were treated with acupuncture 24 h preoperatively. Follow-up checkups were conducted intraoperatively, postoperatively, and on the third day. RESULTS: There was no difference between men; there was a difference between women. Visual analog scale score was lower in group A at the intraoperative third and fifth minutes (0.00 vs. 1 and 0.00 vs. 0.5). Analgesic consumption was lower in group A at the end of third day (p = 0.024). Postoperative IL-17 levels were higher than preoperative levels in group A (23.58 vs. 19.33). Postoperative IL-23 levels were lower than preoperative levels in group A (13.66 vs. 29.51). Group C showed increased postoperative IL-23 levels (28.81 vs. 33.51). Preoperative IL-17 and postoperative IL-23 levels were lower in group A than in group C (19.33 vs. 27.69 and 13.66 vs. 33.51). Although no difference was observed between group A and group C in preoperative saphenous vein diameter, postoperative saphenous vein diameter was smaller in group A (p = 0.008). Saphenous vein diameter was smaller on day 3 in group A than in group C (p = 0.043). CONCLUSION: Acupuncture is effective on acute pain and level of IL-23 in the treatment of endovenous ablation using cyanoacrylate.

Long-term results of micropulse laser trabeculoplasty with 577-nm yellow wavelength in patients with uncontrolled primary open-angle glaucoma and pseudoexfoliation glaucoma.

Our aim was to evaluate the long-term results of micropulse laser trabeculoplasty (MLT) with 577-nm yellow wavelength in the treatment of glaucoma. We reviewed the medical records of 51 patients (51 eyes) with uncontrolled primary open-angle glaucoma or pseudoexfoliation glaucoma who underwent 180° MLT for the first time. The success of MLT was defined as an IOP reduction of ≥ 20% and IOP < 21 mmHg after treatment. If the number of medications was increased or further laser trabeculoplasty or glaucoma surgery was required after treatment, the case was considered unsuccessful. The mean duration of patient follow-up was 18.39 ± 12.17 months (range 3-52 months). Patients included in the study used 2-4 types of antiglaucoma eye drops (mean 3.43 ± 0.7). The mean number of MLT spots was 65.54 ± 6.19, and the mean energy level was 750.98 ± 101.73 mJ. The decrease in intraocular pressure compared to baseline measurements was: 16.72 ± 11.87%, 15.07 ± 13.76%, 12.63 ± 14.29%, 16.66 ± 19.32%, and 16.75 ± 19.78% during follow-up at 3, 6, 12, 24, and 36-48 months. Successful response was achieved in 35.41%, 36.95%, 34.21%, 40%, 41.17%, and 42.85% of patients during 3, 6, 12, 18, 24, and 36-48 months of follow-ups, respectively. Of the 51 eyes studied, 12 patients (23.5%) underwent post-MLT glaucoma surgery, and 7 patients (13.7%) had cataract surgery, whose follow-up data were subsequently censored. The reduction of intraocular pressure showed a significant correlation with baseline intraocular pressure, while age and laser power showed no correlation (p > 0.05). MLT is a novel treatment option for patients with glaucoma with favorable long-term outcomes and a good safety profile.

Death receptor-dependent apoptosis and cell cycle delay induced by bioymifi in human cervical cancer cells.

In chemotherapy applied against cervical cancer, non-specific cytotoxicity and drug resistance that develops over time are trying to be overcome. Therefore, the development of effective and innovative chemotherapeutic drugs for the treatment is among the priority issues in the medical field. The anticancer activity of the Bioymifi, which can activate apoptosis by inducing DR-5 clustering and aggregation against the human cervical cancer cell line, was investigated in the current study. The cytotoxic activity of Bioymifi on the HeLa cell line was identified using XTT assay. The pathway of the cell death mechanism was analyzed through the cell cycle and Annexin V assays by the flow cytometry. DAPI staining assay was applied under fluorescence microscopy to examine the nuclear morphology. Bioymifi appeared to have a remarkable IC50 value (11.75µM) against HeLa cells. The cell cycle analysis demonstrated the increase of Bioymifi cured HeLa cells in the S phase. And also, 11.75µM of Bioymifi caused a significantly higher apoptotic effect compared to control. In addition, in vitro immunofluorescence experiments of this study represented that Bioymifi reduced Ki-67 localization in HeLa cells. Bioymifi has significantly anticancer actions in Human cervix cancer in vitro and can be combined with standard treatment.

Addressing the System-Size Dependence of the Local Approximation Error in Coupled-Cluster Calculations.

Over the last two decades, the local approximation has been successfully used to extend the range of applicability of the "gold standard" singles and doubles coupled-cluster method with perturbative triples CCSD(T) to systems with hundreds of atoms. The local approximation error grows in absolute value with the increasing system size, i.e., by increasing the number of electron pairs in the system. In this study, we demonstrate that the recently introduced two-point extrapolation scheme for approaching the complete pair natural orbital (PNOs) space limit in domain-based pair natural orbital CCSD(T) calculations drastically reduces the dependence of the error on the system size, thus opening up unprecedented opportunities for the calculation of benchmark quality relative energies for large systems.

Design, synthesis, and anticancer activity of novel 4-thiazolidinone-phenylaminopyrimidine hybrids.

4-Thiazolidinones and phenylaminopyrimidines are known as anticancer agents. Imatinib is the pioneer phenylaminopyrimidine derivative kinase inhibitor, which is used for the treatment of chronic myeloid leukemia. With a hybrid approach, a novel series of 5-benzylidene-2-arylimino-4-thiazolidinone derivatives containing phenylaminopyrimidine core were designed, synthesized, and tested for their anticancer activity on K562 (chronic myeloid leukemia), PC3 (prostat cancer), and SHSY-5Y (neuroblastoma) cells. Since superior anticancer activity was observed on K562 cells, further biological studies of selected compounds (8, 15, and 34) were performed on K562 cells. For the synthesis of designed compounds, thiourea compounds were converted to 2-imino-1,3-thiazolidin-4-ones with α-chloroacetic acid in the presence of sodium acetate. 5-Benzylidene-2-imino-1,3-thiazolidin-4-one derivatives were obtained by Knoevenagel condensation of 2-imino-1,3-thiazolidin-4-ones with related aldehydes. Compounds 8, 15, and 34 were evaluated for cell viability, apoptosis studies, cell cycle experiments, and DNA damage assays. IC50 values of compounds 8, 15, and 34 were found as 5.26 ± 1.03, 3.52 ± 0.91, and 8.16 ± 1.27 µM, respectively, in K562 cells. Preferably, these compounds showed less toxicity towards L929 cells compared to imatinib. Furthermore, compounds 8 and 15 significantly induced early and late apoptosis in a time-dependent manner. Compounds 15 and 34 induced cell cycle arrest at G0/G1 phase and compound 8 caused cell cycle arrest at G2/M phase. Based on DNA damage assay, compounds 8 and 15 were found to be more genotoxic than imatinib towards K562 cells. To put more molecular insight, possible Abl inhibition mechanisms of most active compounds were predicted by molecular docking studies. In conclusion, a novel series of 5-benzylidene-2-arylimino-4-thiazolidinone derivatives and their promising anticancer activities were reported herein.

The Impact of Everolimus and Radiation Therapy on Pulmonary Fibrosis.

Background and objectives: Everolimus (EVE) is a mammalian target of the rapamycin (mTOR) inhibitor that is widely used in cancer patients. Pulmonary toxicity, usually manifesting as interstitial pneumonitis, is a serious adverse effect of this drug. Radiation therapy, which is often administered in conjunction with chemotherapy for synergistic effects, also causes pulmonary fibrosis. In view of pulmonary damage development in these two forms of cancer treatment, we have examined the effect of EVE administration individually, in combination with radiation given in varying sequences, and its relation to the extent of pulmonary damage. Materials and Methods: We performed an experimental study in albino rats, which were randomized into five groups: (1) control group, (2) EVE alone, (3) EVE 22 h after radiation, (4) EVE 2 h after irradiation, and (5) only radiation. Sixteen weeks after thoracic irradiation, rat lung tissue samples were examined under light microscopy, and the extent of pulmonary damage was estimated. After this, we calculated median fibrosis scores in each group. Results: The highest fibrosis score was noted in Group 4. Among the five groups, the control group had a significantly lower median fibrosis score compared to the others. When the median fibrosis score of the group that received concurrent EVE with radiation therapy (RT) (Group 4) was compared with that of the control group, the difference was statistically significant (p = 0.0022). However, no significant differences were achieved among the study groups that received EVE only or RT only, whether concurrently or sequentially (p > 0.05). Conclusion: EVE is an effective treatment option for the management of several malignancies and is often combined with other therapies, such as radiation, for a more efficient response. However, an increased risk of pulmonary fibrosis should also be anticipated when these two modalities are combined, as they both can cause pulmonary damage, especially when administered concurrently.

In vitro comparison of the cytotoxic effects of statins on U266 myeloma cell line.

Background & objectives: Statins are one of the most widely used drugs and have antilipidemic effects as well as antioxidant, anti-inflammatory, anti-angiogenic and anti-tumorigenic effects. It has been shown that the synergistic combinations of statins which can provide better clinical benefit in the treatment of cancer and if administered with other anticancer agents, may be an alternative treatment modality. The aim of this study was to assess the efficacy of administrating statin in multiple myeloma (MM) cell line on cell proliferation. Methods: U266 myeloma cells were cultured in 25 or 75 cm[2] flasks by using cell culture medium mixtures obtained with the supplementation of 10 per cent foetal bovine serum and one per cent of penicillin-streptomycin into RPMI 1640 medium. When the cells reached confluence (reached to the density of 70%), they were reproduced by passaging. Cytotoxicity was evaluated by using the XTT test. Results: Statins (atorvastatin and simvastatin), were administered to the U266 myeloma cell line at 100, 50, 25, 12.5, 6.25 and 3.12 µM concentrations. Inhibitor concentration 50 (IC50) values calculated for atorvastatin and simvastatin were determined as 94 and 38 µM, respectively. While 100, 50, 25, 12.5, 6.25 and 3.12 µM concentrations were used for bortezomib, the IC50value calculated for this agent was 18.2 nM. When six concentrations of bortezomib used in the study were combined with 12.5 µM inactive concentrations of statins that did not cause inhibition in cell proliferation, both atorvastatin and simvastatin increased the effect of bortezomib at all the concentrations used, and simvastatin showed a stronger efficacy than atorvastatin. Interpretation & conclusions: Our in vitro results indicated that atorvastatin and simvastatin when used along with the conventional treatment in myeloma patients, may improve the effectiveness of the standard therapy and prevent the bortezomib-induced cytotoxic and neurotoxic side effects when used at a low dose. Further studies need to be done in MM patints to confirm these findings.

London Dispersion Interactions in Pnictogen Cations [ECl2 ]+ and [E=E]2+ (E=P, As, Sb) Supported by Anionic N-Heterocyclic Carbenes.

Several pnictogen dihalide complexes of the type (WCA-IDipp)EX2 (E=P, As, Sb; X=Cl, Br) that bear an anionic N-heterocyclic carbene ligand with a weakly coordinating borate moiety (WCA-IDipp, WCA=B(C6 F5 )3 , IDipp=1,3-bis(2,6-diisopropylphenyl)imidazolin-2-ylidene) were prepared by salt metathesis reactions between the respective pnictogen trihalides EX3 and the lithium salt (WCA-IDipp)Li⋅toluene. Two-electron reduction of the dihalides (WCA-IDipp)EX2 with 1,3-bis(trimethylsilyl)-1,4-dihydropyrazine or elemental magnesium afforded the dipnictenes (WCA-IDipp)2 E2 , which display typical element-element double bonds as observed in diaryldiphosphenes, -arsenes and -stibenes. To provide an insight into the factors contributing to the structural stability of the pnictogen dihalide and dipnictene compounds, quantum chemical calculations were performed at the domain-based local pair natural orbital coupled-cluster (DLPNO-CCSD(T)) level. A local energy decomposition (LED) analysis of the interaction between the carbene and the pnictogen dihalide or dipnictene moiety demonstrates that London dispersion is an essential factor for the stabilization of these compounds.

Local energy decomposition analysis of hydrogen-bonded dimers within a domain-based pair natural orbital coupled cluster study.

The local energy decomposition (LED) analysis allows for a decomposition of the accurate domain-based local pair natural orbital CCSD(T) [DLPNO-CCSD(T)] energy into physically meaningful contributions including geometric and electronic preparation, electrostatic interaction, interfragment exchange, dynamic charge polarization, and London dispersion terms. Herein, this technique is employed in the study of hydrogen-bonding interactions in a series of conformers of water and hydrogen fluoride dimers. Initially, DLPNO-CCSD(T) dissociation energies for the most stable conformers are computed and compared with available experimental data. Afterwards, the decay of the LED terms with the intermolecular distance (r) is discussed and results are compared with the ones obtained from the popular symmetry adapted perturbation theory (SAPT). It is found that, as expected, electrostatic contributions slowly decay for increasing r and dominate the interaction energies in the long range. London dispersion contributions decay as expected, as r-6. They significantly affect the depths of the potential wells. The interfragment exchange provides a further stabilizing contribution that decays exponentially with the intermolecular distance. This information is used to rationalize the trend of stability of various conformers of the water and hydrogen fluoride dimers.

Epistatic adaptive evolution of human color vision.

Establishing genotype-phenotype relationship is the key to understand the molecular mechanism of phenotypic adaptation. This initial step may be untangled by analyzing appropriate ancestral molecules, but it is a daunting task to recapitulate the evolution of non-additive (epistatic) interactions of amino acids and function of a protein separately. To adapt to the ultraviolet (UV)-free retinal environment, the short wavelength-sensitive (SWS1) visual pigment in human (human S1) switched from detecting UV to absorbing blue light during the last 90 million years. Mutagenesis experiments of the UV-sensitive pigment in the Boreoeutherian ancestor show that the blue-sensitivity was achieved by seven mutations. The experimental and quantum chemical analyses show that 4,008 of all 5,040 possible evolutionary trajectories are terminated prematurely by containing a dehydrated nonfunctional pigment. Phylogenetic analysis further suggests that human ancestors achieved the blue-sensitivity gradually and almost exclusively by epistasis. When the final stage of spectral tuning of human S1 was underway 45-30 million years ago, the middle and long wavelength-sensitive (MWS/LWS) pigments appeared and so-called trichromatic color vision was established by interprotein epistasis. The adaptive evolution of human S1 differs dramatically from orthologous pigments with a major mutational effect used in achieving blue-sensitivity in a fish and several mammalian species and in regaining UV vision in birds. These observations imply that the mechanisms of epistatic interactions must be understood by studying various orthologues in different species that have adapted to various ecological and physiological environments.

Dacryoadenitis and extraocular muscle inflammation associated with contact lens-related Acanthamoeba keratitis: A case report and review of the literature.

The present report discusses a new case of dacryoadenitis with extraocular muscle inflammation associated with Acanthamoeba keratitis (AK) in a contact lens wearer. A 41-year-old male, who has worn silicone hydrogel contact lenses on an extended basis for about 10 years, attended with the complaints of vision disturbance, hyperemia, and pain in his right eye. His history revealed that 1.5 month ago, he had been diagnosed with allergic conjunctivitis and had used steroid eye drops. Biomicroscopic examination revealed eyelid edema, chemosis, and ring infiltration, radial keratoneuritis and an epithelial defect in the cornea. Magnetic resonance imaging demonstrated enlarged lacrimal gland with edematous changes consistent with inflammation due to dacryoadenitis. There were also thickening and edema of the right superior oblique and lateral rectus muscle. The treatment protocol for AK was applied with no specific treatment for dacryoadenitis. After 4 months of the treatment, dacryoadenitis and keratitis regressed. Dacryoadenitis and extraocular muscle inflammation may accompany AK more frequently than expected and previously known. The evaluation of the lacrimal gland and extraocular muscles in presence of AK might be beneficial for understanding better the exact clinical picture and course of the keratitis.

A simple method for studying the molecular mechanisms of ultraviolet and violet reception in vertebrates.

BACKGROUND: Many vertebrate species use ultraviolet (UV) reception for such basic behaviors as foraging and mating, but many others switched to violet reception and improved their visual resolution. The respective phenotypes are regulated by the short wavelength-sensitive (SWS1) pigments that absorb light maximally (λmax) at ~360 and 395-440 nm. Because of strong epistatic interactions, the biological significance of the extensive mutagenesis results on the molecular basis of spectral tuning in SWS1 pigments and the mechanisms of their phenotypic adaptations remains uncertain. RESULTS: The magnitudes of the λmax-shifts caused by mutations in a present-day SWS1 pigment and by the corresponding forward mutations in its ancestral pigment are often dramatically different. To resolve these mutagenesis results, the A/B ratio, in which A and B are the areas formed by amino acids at sites 90, 113 and 118 and by those at sites 86, 90 and 118 and 295, respectively, becomes indispensable. Then, all critical mutations that generated the λmax of a SWS1 pigment can be identified by establishing that 1) the difference between the λmax of the ancestral pigment with these mutations and that of the present-day pigment is small (3 ~ 5 nm, depending on the entire λmax-shift) and 2) the difference between the corresponding A/B ratios is < 0.002. CONCLUSION: Molecular adaptation has been studied mostly by using comparative sequence analyses. These statistical results provide biological hypotheses and need to be tested using experimental means. This is an opportune time to explore the currently available and new genetic systems and test these statistical hypotheses. Evaluating the λmaxs and A/B ratios of mutagenized present-day and their ancestral pigments, we now have a method to identify all critical mutations that are responsible for phenotypic adaptation of SWS1 pigments. The result also explains spectral tuning of the same pigments, a central unanswered question in phototransduction.

The effects of endocannabinoid receptor agonist anandamide and antagonist rimonabant on opioid analgesia and tolerance in rats.

The role of the cannabinoid (CB) system in the tolerance to analgesic effect of opioid remains obscure. The aim of the present study was to evaluate the effects of the endocannabinoid nonselective receptor agonist anandamide (AEA) and CB1 receptor antagonist rimonabant (SR141716) on morphine analgesia and tolerance in rats. Male Wistar albino rats weighing 215-230 g were used in these experiments. To constitute morphine analgesic tolerance, a 3-day cumulative dosing regimen was used. The analgesic effects of AEA (10 mg/kg), SR141716 (10 mg/kg), and morphine (5 mg/kg) were considered at 30-min intervals by tail flick (TF) and hot plate (HP) analgesia tests. The analgesic effects of the drugs were measured as TF and HP latencies in all groups for each rat and converted to %MPE. The data were analysed by analysis of variance followed by Tukey test. The findings suggested that AEA in combination with morphine produced a significant increase in expression of analgesic tolerance to morphine. Conversely, cannabinoid receptor antagonist SR141716 attenuated morphine analgesic tolerance. In addition, administration of AEA with morphine increased morphine analgesia. In conclusion, we observed that the cannabinoid receptor agonist anandamide and CB1 receptor antagonist SR141716 plays a significant role in the opioid analgesia and tolerance.

Contact Lens-Related Acanthamoeba Keratitis and Accompanying Dacryoadenitis.

OBJECTIVES: In this study, by presenting four cases, we aimed to discuss the clinical presentation, diagnosis, therapy, and methods for prevention of Acanthamoeba keratitis (AK) and to emphasize that inflammatory dacryoadenitis can be seen together with it. METHODS: This is a retrospective case series of four eyes of four wearers of hydrophilic soft contact lenses who developed AK. The diagnosis was based on clinical signs, disease course, and confocal microscopy results. In cases with dacryoadenitis, in addition to clinical findings, magnetic resonance imaging was used to establish the diagnosis. RESULTS: All of the cases were using their contact lenses without supervision of an ophthalmologist under inappropriate conditions such as swimming in a pool and during steam bath. The diagnosis was established, and the treatment was performed within the standard protocol for AK. Two of the patients had low visual acuity at the level of counting fingers with corneal scar, cataract, and glaucoma, whereas the other two healed with fewer complications and achieved better vision. Two of the 4 cases (50%) presented with dacryoadenitis accompanying the AK. Lacrimal gland swelling improved in conjunction with symptoms of keratitis without specific treatment for dacryoadenitis in these two cases. CONCLUSIONS: Despite the improvements in diagnostic tests and treatment strategies for AK, the role of prevention becomes apparent because of the bad prognosis of this serious complication; thus, contact lens wearers should be aware of the importance of using lenses under ophthalmologist's supervision. In addition, we would like to emphasize that AK may be frequently associated with lacrimal gland inflammation.

Success of hydrocone (TORIS-K) soft contact lens for keratoconus and traumatic keratopathy.

OBJECTIVE: To present success of Toris-K contact lenses in keratoconus and traumatic keratopathy with irregular corneal surface. METHODS: Toris-K contact lenses were used to treat 7 eyes of 4 patients with traumatic keratopathy (Case 1) or keratoconus (Case 2, Case 3, and Case 4). All cases had a complete eye examination before the contact lens application. The case with traumatic keratopathy was a 32-year-old male who had corneal penetrating injury due to hobnail strike 23 months ago. The other 3 keratoconus cases were females at the age of 14, 16 and 22 years old. They had high myopia and irregular astigmatism due to keratoconus. All patients refused using rigid gas permeable contact lens because of intolerance. Toris-K contact lenses were fitted on all eyes. All patients were followed-up for 28 months with a complete ophthalmic examination and corneal topography every two months. RESULTS: Improvement of BCVA of the cases was remarkable. All cases were comfortable with their Toris-K contact lenses for 28 months. There was no significant distortion on the lenses during follow-up period. CONCLUSION: Toris-K lenses may be an effective alternative treatment option for the patients with keratoconus and traumatic keratopathy, especially who cannot tolerate rigid gas permeable contact lenses.

Unilateral morning glory optic disc anomaly in a case with Down syndrome.

BACKGROUND: This case is unique because it is the first reported case of Down syndrome with morning glory optic disc anomaly in literature. CASE PRESENTATION: A 15-year-old girl with features of Down syndrome presented to the Clinic of Ophthalmology for a regular ophthalmologic examination. Her best corrected visual acuity was 20/50 in the right eye and 20/20 in the left eye. The fundus examination revealed findings compatible with unilateral morning glory optic disc anomaly in the right eye. The patient underwent a complete ophthalmologic and systemic evaluation to explore possible associated findings. CONCLUSION: This case report emphasizes the importance of ophthalmic screening-examinations in Down children to rule out any vision relevant pathology.

Confocal scanning laser tomography of the optic nerve head on the patients with Alzheimer's disease compared to glaucoma and control.

The purpose of this study was to evaluate optic nerve head (ONH) differences of the patients with Alzheimer's disease (AD) measured by confocal scanning laser tomography [Heidelberg Retina Tomograph (HRT) III] and compare with glaucoma and control subjects. Eighty-four patients were enrolled into the study: 44 eyes of 24 patients with mild to moderate AD (Group 1), 68 eyes of 35 patients with glaucoma (Group 2), and 49 eyes of 25 heathy volunteers as a control (Group 3). A complete ophthalmologic examination as well as a confocal scanning laser ophthalmoscopic assessment with HRT III were performed on all patients. Mean values of the ONH topographic parameters such as rim area (RA), rim volume (RV), height variation contour, linear cup/disc ratio, cup shape measure, and retinal nerve fiber layer (RNFL) were recorded. Mean values of RNFL thickness was 0.23 ± 0.07 in AD, 0.22 ± 0.09 in glaucoma and 0.24 ± 0.07 in the control group (p = 0.323). RA and RV were significantly lower, and linear C/D ratio was significantly higher in the glaucoma group when compared to AD and control (p < 0.05). There was no statistically significant difference between AD and control for the optic disc parameters tested (p > 0.05). We observed a negative correlation of the age with RNFL in all of the groups (p < 0.005). Age was the most important parameter affecting RNFL. Our results suggest that HRT does not demonstrate ONH differences between AD and control group, while it successfully differentiates glaucoma from AD and control cases of older age.