Dry eye syndrome symptoms in patients with psoriasis.

BACKGROUND: Psoriasis is one of the most common dermatoses associated with a variety of comorbidities. There have been some reports on its possible association with ocular disorders however dry eye syndrome (DES) in such patients has been poorly investigated. OBJECTIVES: To investigate the frequency of DES symptoms in psoriatic patients, also regarding psoriasis severity in PASI, manifestation and therapy. METHODS: 40 patients with psoriasis and 40 volunteers without dermatoses were enrolled in the study. They completed Ocular Surface Disease Index (OSDI) questionnaire and were objectively examined by IDRA® device to perform automatic interferometry, automatic meibography of lower eyelid glands, non-invasive break-up time (NIBUT), blink quality and tear meniscus height. RESULTS: Patients with psoriasis had statistically significantly thicker lipid layer (p = 0.0042 left eye, p = 0.0313 right eye) and greater loss of Meibomian glands compared to controls (p = 0.0128 left eye, p = 0.048 right eye). The patients had lower, although insignificantly, eye blink quality and tear meniscus height than the control group, as well as shorter NIBUT and higher score in OSDI. After the division of patients into two groups-with or without nails involvement/psoriatic arthritis/systemic treatment- we did not observe any significant differences between the groups. PASI did not correlate with any DES parameter. CONCLUSIONS: This is the first study of DES symptoms with an objective IDRA® analyzer. We managed to observe that patients with psoriasis have thicker lipid layer and higher Meibomian glands' loss in lower eyelids. Based on all assessed objective and subjective parameters psoriatics do not seem to have an increased risk of DES. The presence of psoriatic arthritis or nail involvement does not seem to be a predisposing factor for DES development. PASI probably cannot be a prognostic factor for any of the DES-associated parameters. Nevertheless, DES in psoriasis requires further research on bigger samples to establish reliable recommendations.

The immunology of corneal limbal stem cells: the up-to-date approach to stem cell transplantation.

Limbal epithelial stem cells (LSC, LESC) are multipotent cells used as regenerative treatment of the cornea in patients with limbal epithelial stem cell deficiency (LSCD, LESCD). There are different types of stem cell grafting including cultivated limbal epithelial transplantation (CET) and simple limbal epithelial transplantation (SLET). The outcomes of the techniques have been assessed as similar, with differences in the sample size required during the procedures. The most important culture components for stem cell cultivation include 3T3 murine fibroblasts, human amniotic membrane (HAM), fibrin gel, and culture medium. The culture medium may be enriched with serum or not; however, xenobiotic-free materials are preferred because of the low risk of pathogen transmission. Multiple studies have defined molecules important for maintaining the function of LSC including C/EBP δ, Bmi-1, p63 α, interleukins (IL-6), epithelial structural proteins - keratins, and antibodies against epidermal growth factor receptor (EGFR). The cell phenotype of LSC has been described with factors of transplantation success rate such as a high percentage of p63 positive cells. The article emphasizes the role of recipient tissue preparation, modern cultivation techniques and pathophysiological processes in LSC transplantation effectiveness.

Novel approach to antiangiogenic factors in age-related macular degeneration therapy.

Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss among the population above 85 worldwide. There are two main types of AMD: neovascular and dry AMD. Neovascular AMD leads to macular changes resulting from abnormal choroidal neovascularization. Untreated neovascular AMD leads to scar formation and irreversible sight deterioration. Dry AMD in consequence leads to atrophic changes of the macula. The last decades brought a breakthrough in the therapy of neovascular age-related macular degeneration by introduction of, firstly, photodynamic therapy and, later, anti-VEGF agents administered intravitreally in order to stop neoangiogenesis. However, the treatment of dry AMD is still challenging. Among the directions in dry AMD treatment, the most promising are complement cascade inhibitors and complement cascade targeted gene therapy. In the article we outline the main directions in up-to-date experimental and practical approaches to wet and dry AMD therapy with the emphasis on antiangiogenic factors and gene therapy focused on the inhibition of pathological angiogenesis.

New perspectives of immunomodulation and neuroprotection in glaucoma.

Glaucoma is the neurodegenerative disease of retinal ganglion cells. The main risk factor for glaucoma is increased intraocular pressure. The processes leading to cell death due to presence of the injury factor comprise multiple molecular mechanisms, as well as the immunological response. The knowledge of immunological mechanisms occurring in glaucomatous degeneration makes it possible to introduce glaucoma treatment modulating the cellular degradation. The glaucoma treatment of the future will make it possible not only to lower the intraocular pressure, but also to moderate the intracellular mechanisms in order to prevent retinal cell degeneration. Citicoline is a drug modulating glutamate excitotoxicity that is already in use. Rho kinase inhibitors were found to stimulate neurite growth and axon regeneration apart from lowering intraocular pressure. The complementary action of brimonidine is to increase neurotrophic factor (NTF) concentrations and inhibit glutamate toxicity. Immunomodulatory therapies with antibodies and gene therapies show promising effects in the current studies. The supplementation of NTFs prevents glaucomatous damage. Resveratrol and other antioxidants inhibit reactive oxygen species formation. Cell transplantation of stem cells, Schwann cells and nerve extracts was reported to be successful so far. Our review presents the most promising new strategies of neuroprotection and immunomodulation in glaucoma.

Systemic immunosuppression with mycophenolate mofetil to prevent corneal graft rejection after high-risk penetrating keratoplasty: a 2-year follow-up study.

PURPOSE: In this study, we aimed to evaluate the efficacy and safety of systemic immunosuppression with mycophenolate mofetil (MMF) to prevent corneal graft rejection after high-risk penetrating keratoplasty. METHODS: One hundred and ninety-six consecutive patients who underwent high-risk penetrating keratoplasty defined as the presence of deep vascularization in more than two quadrants, keratouveitis, emergency keratoplasties, and retransplantations were enrolled in the study. Ninety-eight prospectively followed up patients were treated with MMF [with dose adjustment based on mycophenolic acid (MPA) serum concentration], and 98 patients were in the non-MMF-treated retrospectively assessed control group. RESULTS: During a mean of 24 months of observation, immune reactions occurred in eight cases (8 %) and graft rejection with subsequent graft failure occurred in three cases (3 %) in the MMF group. In the control group, graft rejection occurred in 76 cases (78 %) and failure due to graft rejection occurred in 30 cases (31 %). Kaplan-Meier analysis demonstrated that 93 % of the grafts in the MMF-treated group and 47 % in the control group showed no immune rejection (p < 0.01, log-rank test) after a year. Cox regression analysis proved that MMF treatment decreased the risk of graft rejection 11 times (RR = 11, 95.0 % CI 4.8-25, p < 0.0001). Among 98 MMF-treated patients, 13 had gastric discomfort, three developed leucopenia, and two had anemia that resolved after MMF dose reduction. CONCLUSIONS: MMF treatment after high risk penetrating keratoplasty is safe and reduces the incidence of immune graft rejection and graft failure. Side effects were rare and reversible in all but one case.

Polymorphism of the APEX nuclease 1 gene in keratoconus and Fuchs endothelial corneal dystrophy.

Human APEX nuclease 1 (APEX1) plays an important role in the repair of oxidative DNA lesions through base excision repair. It may influence the development of oxidative stress-related diseases. The aim of this study was to determine the relationship between the genotypes of the c.444 T>G (rs1130409) and c.-468 T>G (rs1760944) polymorphisms in the APEX1 gene and the occurrence of two oxidative stress-related eye diseases: keratoconus (KC) and Fuchs endothelial corneal dystrophy (FECD). The study involved 250 patients with KC, 209 patients with FECD, and 350 control subjects. All of the patients and control subjects underwent a detailed ophthalmic examination. The polymorphisms were genotyped by mismatch polymerase chain reaction restriction fragment length polymorphism (mismatch PCR-RFLP). We observed that the G/T and T/T genotypes of the c.-468 T>G polymorphism were respectively associated with a decreased occurrence of KC (OR 0.54, 95% CI 0.37-0.95; p = 0.030) and an increased occurrence of KC (OR 1.87, 95% CI 1.06-3.32; p = 0.032). None of these polymorphisms showed any association with FECD. Furthermore, no other association was observed, including haplotypes of the two polymorphisms. Our findings suggest that the c.-468 T>G polymorphism of the APEX1 gene may play a role in the pathogenesis of KC.

Polymorphisms of the apoptosis-related FAS and FAS ligand genes in keratoconus and Fuchs endothelial corneal dystrophy.

Keratoconus (KC) is a non-inflammatory eye disease characterized by progressive corneal thinning and asymmetrical conical protrusion of the cornea. Fuchs endothelial corneal dystrophy (FECD) is a degenerative, slowly progressive disease of the corneal endothelium that is characterized by alteration in corneal endothelial cell morphology and progressive loss of these cells. They are unrelated eye diseases that may ultimately lead to vision loss. Their pathogenesis is largely unknown, although impaired apoptosis has been suggested to be responsible for both diseases. Therefore, we studied the frequency of the c.-671A>G polymorphism of the apoptosis-related FAS gene and the c.-844T>C polymorphism of the FAS ligand (FASLG) gene in patients with FECD (221 individuals) or KC (264) and controls (300). Each polymorphism is located within the putative cis-acting element of the respective promoter. Risk of KC or FECD was estimated with unconditional multiple logistic regression with adjustment for various factors, including age, sex, allergies, and family history. The T/T genotype and the T allele of the c.-844T>C polymorphism were associated with increased occurrence of KC, while the C allele was associated with decreased KC occurrence. The G allele of the c.-671A>G polymorphism was associated with increased occurrence of FECD, while the A allele was associated with decreased FECD occurrence. The C/C-A/A combined genotype was associated with reduced risk of FECD, whereas the T/T-G/A combined genotype increased risk of KC. In conclusion, variability in the expression of the FAS and FASLG genes may be involved in the pathogenesis of KC and FECD.

Polymorphism of the DNA base excision repair genes in keratoconus.

Keratoconus (KC) is a degenerative corneal disorder for which the exact pathogenesis is not yet known. Oxidative stress is reported to be associated with this disease. The stress may damage corneal biomolecules, including DNA, and such damage is primarily removed by base excision repair (BER). Variation in genes encoding BER components may influence the effectiveness of corneal cells to cope with oxidative stress. In the present work we genotyped 5 polymorphisms of 4 BER genes in 284 patients and 353 controls. The A/A genotype of the c.-1370T>A polymorphism of the DNA polymerase γ (POLG) gene was associated with increased occurrence of KC, while the A/T genotype was associated with decreased occurrence of KC. The A/G genotype and the A allele of the c.1196A>G polymorphism of the X-ray repair cross-complementing group 1 (XRCC1) were associated with increased, and the G/G genotype and the G allele, with decreased KC occurrence. Also, the C/T and T as well as C/C genotypes and alleles of the c.580C>T polymorphism of the same gene displayed relationship with KC occurrence. Neither the g.46438521G>C polymorphism of the Nei endonuclease VIII-like 1 (NEIL1) nor the c.2285T>C polymorphism of the poly(ADP-ribose) polymerase-1 (PARP-1) was associated with KC. In conclusion, the variability of the XRCC1 and POLG genes may play a role in KC pathogenesis and determine the risk of this disease.

Polymorphism of the flap endonuclease 1 gene in keratoconus and Fuchs endothelial corneal dystrophy.

Oxidative stress is implicated in the pathogenesis of many diseases, including serious ocular diseases, keratoconus (KC) and Fuchs endothelial corneal dystrophy (FECD). Flap endonuclease 1 (FEN1) plays an important role in the repair of oxidative DNA damage in the base excision repair pathway. We determined the association between two single nucleotide polymorphisms (SNPs), c.-441G>A (rs174538) and g.61564299G>T (rs4246215), in the FEN1 gene and the occurrence of KC and FECD. This study involved 279 patients with KC, 225 patients with FECD and 322 control individuals. Polymerase chain reaction (PCR) and length polymorphism restriction fragment analysis (RFLP) were applied. The T/T genotype of the g.61564299G>T polymorphism was associated with an increased occurrence of KC and FECD. There was no association between the c.-441G>A polymorphism and either disease. However, the GG haplotype of both polymorphisms was observed more frequently and the GT haplotype less frequently in the KC group than the control. The AG haplotype was associated with increased FECD occurrence. Our findings suggest that the g.61564299G>T and c.-441G>A polymorphisms in the FEN1 gene may modulate the risk of keratoconus and Fuchs endothelial corneal dystrophy.

[Contemporary views on perioperative prophylaxis of postoperative endophthalmitis]. / Wspólczesne poglady na profilaktyke okolooperacyjna pooperacyjnego zapalenia wnetrza galki ocznej.

INTRODUCTION: Post-operative endophthalmitis, although infrequent, leads to severe, often irreversible consequences. For many years in the medical literature there have been reports on the effectiveness of various forms of prevention including antibiotics used. AIM: The aim of this study was to systematize the principles of prevention on the basis of the literature. MATERIAL: Medical reports published in recent years were compared to the conclusions of the European Society of Cataract and Refractive Surgeons (ESCRS) conducted in 16 European countries between 2003 and 2005. RESULTS: The results indicate the lack of a uniform pattern of conduct not only in a global context, but even within European countries. Povidone iodine remains the basis of prophylaxis used before surgery to decontaminate the skin of eyelids and conjunctival sac. Topical antibiotics, mainly the new generation fluoroquinolones, are also commonly used perioperatively. Intracameral injections of cefuroxime at the end of surgery are increasingly used in endophthalmitis prophylaxis. Although their high efficacy and safety have been confirmed a few years ago, the drug formulation intended and registered for use in ophthalmology has been available in most countries since 2013. CONCLUSIONS: Contemporary post-operative endophthalmitis prophylaxis, although varied in different countries, allowed for a significant reduction in the incidence of this complication in recent years. Most ophthalmologists in European countries declare to follow the ESCRS recommendations.

Utilization of the Reinstein ICL Sizing Formula With Hand-held Ultrasound Biomicroscopy Measurements.

PURPOSE: To evaluate the accuracy of the Reinstein formula with hand-held ultrasound biomicroscopy (UBM) measurements for sizing of the Implantable Collamer Lens (ICL). METHODS: A total of 107 myopic eyes of 57 patients implanted with the ICL were included in the study. The size of the ICL was selected based on the manufacturer's recommendations. Agreement between the vault predicted by the Reinstein formula and the vault measured postoperatively was analyzed with Bland-Altman plots. RESULTS: A total of 95% and 81% of patients had a postoperative vault ranging from 150 to 1,000 and 250 to 750 µm, respectively. The mean vault predicted by the Reinstein formula and the postoperative vault in the current study were 580 ± 181 and 547 ± 200 µm, respectively. The size recommendations of the Reinstein formula and the formula provided by the manufacturer, the Kojima formula, and the Dougherty formula overlapped in 50%, 57%, and 49% of eyes, respectively. CONCLUSIONS: The results show that the Reinstein formula combined with a hand-held UBM provides reliable sizing predictions of the ICL. However, considering that robotic UBM measurements have demonstrated a narrower range of deviation in predicting vault depth in previous studies, a direct comparison study between robotic UBM and hand-held UBM measurements is necessary to fully assess the limitations of combining hand-held UBM with the Reinstein formula. [J Refract Surg. 2024;40(3):e142-e147.].

Post-Keratoplasty Microbial Keratitis in the Era of Lamellar Transplants-A Comprehensive Review.

Microbial keratitis in a post-transplant cornea should be considered a distinct entity from microbial keratitis in a non-transplant cornea. Firstly, the use of immunosuppressive treatments and sutures in corneal transplants changes the etiology of keratitis. Secondly, corneal transplant has an impact on corneal biomechanics and structure, which facilitates the spread of infection. Finally, the emergence of lamellar transplants has introduced a new form of keratitis known as interface keratitis. Given these factors, there is a clear need to update our understanding of and management strategies for microbial keratitis following corneal transplantation, especially in the era of lamellar transplants. To address this, a comprehensive review is provided, covering the incidence, risk factors, causes, and timing of microbial keratitis, as well as both clinical and surgical management approaches for its treatment in cases of penetrating and lamellar corneal transplants.

Night-time blood pressure dipping, but not 24-h blood pressure level, is linked to increased 24-h ocular volume slope.

PURPOSE: This study investigated the relationship between blood pressure and intraocular pressure in treatmentnaive, non-glaucoma patients with different blood pressure statuses, focusing on the 24-h ocular volume and nocturnal blood pressure decline. METHODS: Treatment-naive, non-glaucoma patients undergoing hypertension evaluation were enrolled as study participants. Simultaneous 24-h ambulatory blood pressure measurement and 24-h ocular volume recording with a contact lens sensor. We also compared ocular volume curve parameters between normotensive and hypertensive patients, as well as between those with and without nocturnal blood pressure decline. RESULTS: A total of 21 patients, including 7 normotensive and 14 treatment-naive hypertensive individuals, were included in the study. of them, 11 were dippers and 10 were non-dippers. No significant difference in the 24-h ocular volume slope was observed between the hypertensive and normotensive patients (p=0.284). However, dippers had a significantly higher 24-h ocular volume slope (p=0.004) and nocturnal contact lens sensor output (p=0.041) than non-dippers. CONCLUSION: Nocturnal blood pressure decline, rather than the blood pressure level, is associated with the increased 24-h ocular volume slope and nocturnal ocular volume. Further studies are required to determine whether the acceleration of glaucoma progression in dippers is primarily due to low blood pressure, high intraocular pressure, or a combination of both.

Spherical aberrations and their role in modern ophthalmology.

Spherical aberration is an imperfection of the optical system of the human eye. The role of spherical aberration of the human eye in the quality of vision and pseudoaccommodation is reviewed. Spherical aberration is an imperfection of the optical system of the human eye. In most cases, due to well-developed neuroadaptation, it is insignificant for the perception of the image. Nevertheless, its role in modern ophthalmology is far from straightforward. On the one hand, there are clinical scenarios in which an excess of spherical aberration degrades the retinal image and leads to a high dissatisfaction rate among patients.©Recently, there is a growing interest in the modulation of spherical aberration in the clinical setting. Modern intraocular lenses as well as laser refractive procedures are aimed at interfering with spherical aberrations of the optical system in order to increase range of pseudoaccommodation. Here, we review the role of spherical aberration of the human eye in the quality of vision and pseudoaccommodation.

Successive Acanthamoeba Corneal Isolates Identified in Poland Monitored in Terms of In Vitro Dynamics.

BACKGROUND: Amoebae of the genus Acanthamoeba cause a sight-threatening infection called Acanthamoeba keratitis. It is considered a rare disease in humans but poses an increasing threat to public health worldwide, including in Poland. We present successive isolates from serious keratitis preliminary examined in terms of the identification and monitoring of, among others, the in vitro dynamics of the detected strains. METHODS: Clinical and combined laboratory methods were applied; causative agents of the keratitis were identified at the cellular and molecular levels; isolates were cultivated in an axenic liquid medium and regularly monitored. RESULTS: In a phase-contrast microscope, Acanthamoeba sp. cysts and live trophozoites from corneal samples and in vitro cultures were assessed on the cellular level. Some isolates that were tested at the molecular level were found to correspond to A. mauritanensis, A. culbertsoni, A. castellanii, genotype T4. There was variability in the amoebic strain dynamics; high viability was expressed as trofozoites' long duration ability to intense multiply. CONCLUSIONS: Some strains from keratitis under diagnosis verification and dynamics assessment showed enough adaptive capability to grow in an axenic medium, allowing them to exhibit significant thermal tolerance. In vitro monitoring that was suitable for verifying in vivo examinations, in particular, was useful to detect the strong viability and pathogenic potential of successive Acanthamoeba strains with a long duration of high dynamics.

First Report of a Case of Ocular Infection Caused by Purpureocillium lilacinum in Poland.

This report describes the first case of an ocular infection induced by Purpureocillium lilacinum in Poland. The patient was a 51-year-old immunocompetent contact lens user who suffered from subacute keratitis and progressive granulomatous uveitis. He underwent penetrating keratoplasty for corneal perforation, followed by cataract surgery due to rapid uveitic cataract. A few weeks later, intraocular lens removal and pars plana vitrectomy were necessary due to endophthalmitis. The patient was treated with topical, systemic, and intravitreal voriconazole with improvement; however, the visual outcome was poor. The pathogen was identified by MALDI-TOF MS.

Cowpox: How dangerous could it be for humans? Case report.

Cowpox is a rare zoonosis transmitted to humans mainly from cats. The disease usually causes skin lesions; however, the ocular form may lead to other serious complications. We describe a case of cowpox in a rare location of the upper eyelid of an immunocompetent male, which lead to necrosis of the upper eyelid, keratitis and leucomatous opacity, and the neovascularization of the cornea. The patient underwent several surgeries, including reconstruction surgery of the eyelids, correction of the medial canthus, and corneal neurotization with supraorbicular nerve transplantation. Suspicion of cowpox should be made in patients where there are poorly healing skin lesions accompanied by a painful black eschar with erythema and local lymphadenopathy. Ocular cowpox may lead to serious complications and possibly mimic anthrax. Diagnosis of cowpox can be confirmed by detection of cowpox virus DNA by polymerase chain reaction. Patients should be advised to protect themselves while handling sick animals.

Immersion Biometry for Intraocular Lens Power Calculation with Fourth-Generation Formulas.

BACKGROUND: Fourth-generation formulas for intraocular lens power calculations, including the Barrett Universal II formula, the Olsen formula or the Holladay 2 formula, were thoroughly validated with optical biometry measurements. They precisely predict the effective lens position not only in normal eyes but also in eyes with unusual anatomy. However, in the setting of dense nuclear or posterior subcapsular cataracts, optical biometers fail to obtain accurate measurements and third-generation formulas, i.e. the Hoffer Q or the SRK/T, combined with ultrasound measurements are a method of choice. Considering that optical biometry was fine-tuned to immersion ultrasound, we hypothesize that fourth-generation formulas will yield precise intraocular lens power calculations with immersion ultrasound measurements. METHODS: We retrospectively analyzed 50 eyes of 50 patients who underwent uneventful cataract surgery. All patients had intraocular lens power calculated based on immersion ultrasound measurements. Refractive error predictions were compared between third-generation formulas and fourth-generation formulas. RESULTS: There were no statistically significant differences in the median absolute error between formulas. In the study, 86%, 88%, 86%, 84%, 88% and 80% of eyes were within 1 D of target refraction for the SRK/T, the Barrett II, the Hoffer Q, the Holladay 1, the Holladay 2 and the Olsen formula respectively. CONCLUSION: Fourth-generation formulas combined with immersion ultrasound produced similar results to third-generation formulas. However, the percentage of eyes within 1 D of target refraction remains inferior to previously reported results for optical biometry measurements.

[Pseudoexfoliation syndrome (PEX)--a systemic disorder]. / Zespól pseudoeksfoliacji (PEX)-schorzenie ogólnoustrojowe.

Pseudoexfoliation syndrome is an age-related elastosis. The current pathogenetic concept describes PEX as an elastic microfibrillopathy involving TGF-betal, oxidative stress and impaired cellular protection mechanisms as a key pathogenetic factors. Extracellular PEX material is produced, aggregated and accumulated in the anterior segment of the eye. It is also present in the skin, lungs, liver and other visceral organs. These findings suggest that pseudoexfoliation syndrome is a systemic disorder. It is also associated with coronary artery disease, hypertension, Alzheimer's disease and other cardio-vascular problems. The pseudoexfoliation syndrome has been found to be associated with higher mean intraocular pressure, secondary open-angle glaucoma, mature and nuclear cataract. Ocular depositions of pseudoexfoliation material can lead to many intraocular complications. That's why special attention is required before, during and after surgery.

[Levofloxacin (oftaquix) a fluoroquinolone of a new generation in prevention of the postoperative endophthalmitis following uncomplicated cataract surgery--the study of the European Society of Cataract and Refractive Surgeons (ESCRS)]. / Lewofloksacyna (Oftaquix) florochoinolon nowej generacji w zapobieganiu zapalenia wnetrza galki ocznej po niepowiklanych operacjach zacmy--badanie Europejskiego Towarzystwo Chirurgów Zacmy i Chirurgii Refrakcyjnej (European Society of Cataract and Refractive Surgeons--ESCRS).

Randomised multi-centre european clinical trial of antibiotic prophylaxis for endophthalmitis following cataract surgery - study has just begun in Poland. Poland is joining one of the largest prospective european clinical study of antibiotic prophylaxis and the largest in ophthalmology - the ESCRS endophthalmitis prophylaxis clinical trial. Up to 35 000 cataract patients are going to be recruited for this randomized, controlled, multi-centre study in 16 centres from 10 european countries. The goal is to reduce the incidence of endophthalmitis after cataract phacoemusification in Europe to less than 0.05% (less than 1 per 2 000 surgeries). The patients will be divided into four groups; different regimes of two antibiotics: cefuroxime injected intra-camerally and levofloxacine eye drops topically will be compared.