Impact of Systemic Comorbidities on Ocular Hypertension and Open-Angle Glaucoma, in a Population from Spain and Portugal.

Open-angle glaucoma (OAG), the most prevalent clinical type of glaucoma, is still the main cause of irreversible blindness worldwide. OAG is a neurodegenerative illness for which the most important risk factor is elevated intraocular pressure (IOP). Many questions remain unanswered about OAG, such as whether nutritional or toxic habits, other personal characteristics, and/or systemic diseases influence the course of glaucoma. As such, in this study, we performed a multicenter analytical, observational, case-control study of 412 participants of both sexes, aged 40-80 years, that were classified as having ocular hypertension (OHT) or OAG. Our primary endpoint was to investigate the relationship between specific lifestyle habits; anthropometric and endocrine-metabolic, cardiovascular, and respiratory events; and commonly used psychochemicals, with the presence of OHT or OAG in an ophthalmologic population from Spain and Portugal. Demographic, epidemiological, and ocular/systemic clinical data were recorded from all participants. Data were analyzed using the R Statistics v4.1.2 and RStudio v2021.09.1 programs. The mean age was 62 ± 15 years, with 67-80 years old comprising the largest subgroup sample of participants in both study groups. The central corneal thickness (ultrasound pachymetry)-adjusted IOP (Goldman tonometry) in each eye was 20.46 ± 2.35 and 20.1 ± 2.73 mmHg for the OHT individuals, and 15.8 ± 3.83 and 16.94 ± 3.86 mmHg for the OAG patients, with significant differences between groups (both p = 0.001). The highest prevalence of the surveyed characteristics in both groups was for overweight/obesity and daily coffee consumption, followed by psychochemical drug intake, migraine, and peripheral vasospasm. Our data show that overweight/obesity, migraine, asthma, and smoking are major risk factors for conversion from OHT to OAG in this Spanish and Portuguese population.

Treatment of Open-Angle Glaucoma and Ocular Hypertension with Preservative-Free Tafluprost/Timolol Fixed-Dose Combination Therapy: Results from the VISIONARY Study Population in Spain.

Purpose: Data are presented from ophthalmology clinics in Spain participating in the VISIONARY study, examining the effectiveness, tolerability, and safety of the preservative-free tafluprost (0.0015%) and timolol (0.5%) fixed-dose combination (PF tafluprost/timolol FC) in the treatment of OAG and OHT. Methods: An observational, multicenter prospective study examined treatment outcomes following a switch to PF tafluprost/timolol FC in adult OAG/OHT patients demonstrating insufficient response to beta-blocker or prostaglandin analog (PGA) monotherapy. Primary end point was mean change in intraocular pressure (IOP) from baseline at month 6. Changes in the severity of ocular signs and symptoms were also assessed. Results: Overall, 92 patients (51.1% female) were included. Mean (standard deviation) age was 68.3 (12.1) years. Mean IOP was reduced from 21.9 mmHg at baseline to 16.7 mmHg at month 6 (22.3% decrease; P < 0.0001). Significant IOP reductions were observed at weeks 4 and 12 (P < 0.0001). Baseline PGA and beta-blocker users demonstrated mean month 6 IOP reductions of 5.5 mmHg (23.5%; P < 0.001) and 3.5 mmHg (14.6%; P = 0.029), respectively. Severity of conjunctival hyperemia, dry eye, irritation, itching, foreign body sensation, and eye pain was significantly reduced. Three treatment-related adverse events were reported, all were nonserious and mild/moderate in severity. Conclusion: In real-world clinical practice, PF tafluprost/timolol FC treatment provided significant IOP reductions over 6 months and was well tolerated among OAG/OHT patients showing poor response to PGA or beta-blocker monotherapy. IOP-lowering efficacy and improvements in ocular signs and symptoms were evident from week 4 and maintained over the 6-month study period. Trial Registration: European Union electronic Register of Post-Authorisation Studies (EU PAS) register number EUPAS22204.

Detection of occludable angle with anterior segment optical coherence tomography and Pentacam as non-contact screening methods.

PURPOSE: To evaluate diagnostic capacity for occludable anterior chamber angle detection with anterior segment optical coherence tomography (AS-OCT) and Pentacam. METHODS: Observational cross-sectional study with AS-OCT and Pentacam. AS-OCT measures: angle opening distance from Schwalbe line (SL) perpendicular (AOD-SL-Perp) and vertical to iris (AOD-SL-Vert), and iridotrabecular angle (ITA). Pentacam measures: anterior chamber depth (ACD), anterior chamber volume (ACV), and anterior chamber angle (ACA). We analysed Spearman's correlation with gonioscopic classification. Area under receiver operating characteristic curves (AUCs) for occludable angle detection were compared. Agreement between iridocorneal values of methods was evaluated. RESULTS: Seventy-four left eyes of 74 patients. Correlation between temporal AS-OCT and gonioscopy: 0.83 (p < 0.0001) AOD-SL-Perp temporal, 0.82 (p < 0.0001) AOD-SL-Vert temporal, and 0.69 (p < 0.0001) ITA temporal. Correlation between AS-OCT nasal and gonioscopy: 0.74 (p < 0.0001) AOD-SL-Perp nasal, 0.74 (p < 0.0001) AOD-SL-Vert nasal, and 0.70 (p < 0.0001) ITA nasal. Correlation of Pentacam with temporal gonioscopy: 0.57 (p < 0.0001) ACD, 0.56 (p < 0.0001) ACV, and 0.63 (p < 0.0001) ACA. Correlation of Pentacam with nasal gonioscopy: 0.47 (IC 0.27-0.73, p < 0.0001) ACD, 0.49 (p < 0.0001) ACV, and 0.56 (CI 0.38-0.7, p < 0.0001) ACA. AS-OCT AUCs: AOD-SL-Perp temporal 0.89 (CI 0.80-0.95), AOD-SL-Vert 0.87 (CI 0.77-0.94), ITA temporal 0.88 (CI 0.78-0.94), AOD-SL-Perp nasal 0.83 (CI 0.72-0.91), AOD-SL-Vert nasal 0.87 (CI 0.77-0.94), and ITA nasal 0.91 (IC 0.81-0.96). Pentacam AUCs: ACD 0.76 (CI 0.64-0.85), ACV 0.75 (CI 0.63-0.84), and ACA 0.84 (CI 0.74-0.92). No statistical differences between different AUCs. Intraclass correlation coefficient (ICC) of ACA (Pentacam) with ITA temporal (AS-OCT) 0.59 and with nasal ITA nasal (AS-OCT) 0.65. CONCLUSION: Both systems show high capacity for non-contact occludable angle detection. But agreement between methods is moderate or low.

Central retinal vein occlusion in a patient using the antipsychotic drug olanzapine: a case report.

BACKGROUND: We report our findings in a patient who developed central retinal vein occlusion (CRVO) and was a chronic user of olanzapine, an antipsychotic medication. CASE PRESENTATION: A 50-year-old Caucasian man, non-smoker, was referred to our clinic with the chief complaint of floater appearance in his left eye for the past 3 days. His past medical history indicated that he had been taking antipsychotic drugs (olanzapine) for about 3 years, with no other systemic disease or risk factors for CRVO. In the examination, his best-corrected visual acuity (BCVA) was 0.7 in the left eye. The fundus showed signs of nonischemic CRVO with subhyaloid hemorrhage and intraretinal hemorrhage in the posterior pole and superior and inferior retina, without macular edema, confirmed by optical coherence tomography (OCT). We ruled out other probable differential diagnoses and risk factors which lead to CRVO through a complete physical exam and blood analysis (complete blood count, glucose, urea, creatinine, lipid profile, erythrocyte sedimentation rate, C-reactive protein, prothrombin time, partial thromboplastin time, Bleeding time (BT), fibrinogen level, proteins, antiphospholipid antibodies, homocysteine blood level, antithrombin III, protein C and S, factor V Leiden, prothrombin mutation, angiotensin-converting enzyme level, other autoantibodies, and human leukocyte antigen [HLA]-B51). Finally, we confirmed the probable side effect of olanzapine in CRVO, which has not been previously reported. A possible pro-thrombogenic mechanism of olanzapine at the molecular level is an affinity for 5-HT2Aserotonin receptors. Blocking these receptors results in increased platelet aggregation and increased blood coagulability. CONCLUSIONS: These results indicate that CRVO can be a complication of chronic use of antipsychotic medications such as olanzapine, as shown for the first time in our case report. Clinicians should question patients who develop a sudden CRVO whether they are using antipsychotic medications such as olanzapine.

Efficacy and safety study of an eyelid gel after repeated nocturnal application in healthy contact lens users and non-users

PURPOSE: To evaluate skin biocompatibility of a nighttime hydrating eyelid gel and possible ocular surface effects in contact lens users (CLU) and non-contact lens users (NCLU). The formulation is registered as a medical device as Tridocosahexaenoine-AOX(R) (TDHA-AOX) (a concentrated DHA triglyceride), containing also hyaluronic acid (HA). METHODS: A prospective, randomized, masked clinical trial was performed with 62 participants of both sexes, aged 20-70 years, split into: (1) CLU (n = 30) and (2) NCLU (n = 32). All participants were instructed to apply a single dose of the moisturizing gel (containing TDHA-AOX and HA) nightly to the upper and inner eyelids of their right eye (RE) only, and during 2 consecutive weeks. Personal interviews, questionnaires, ophthalmic examinations and reflex tear collection were performed. Ophthalmological parameters included ocular surface response and contact lens status. Levels of satisfaction/adverse events were also recorded. Biochemical parameters included basal and final determination of pro-inflammatory mediator molecules in tear samples by multiplex analyses. Statistics were done by the SPSS 24.0 program. RESULTS: The CLU group had higher OS dysfunction than NCLU, but overall clinical parameters (corneal staining, and Schirmer/FBUT tests) and OSDI scores showed significant improvement in CLU individuals as compared to the NCLU participants, at the end of study. CLDEQ-8 scores pinpointed significant amelioration in initial risk of developing DEs by applying eyelid gel. Multiplex analyses demonstrated significantly lower VEGF expression levels (p < 0,05) in tears among the CLU compared to NCLU after nightly application of eyelid gel. CONCLUSIONS: Eyelid gel appeared to safely and efficiently provide hydration and decongestion of the skin and amelioration of the ocular surface during sleep

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Peripheral vascular disease - a new vascular disease associated with normal tension glaucoma: a case report.

INTRODUCTION: Normal-tension glaucoma is known as a multifactorial optic neuropathy. A number of lines of evidence suggested that vascular factors played a significant role in the development of normal-tension glaucoma. The mechanisms underlying the abnormal ocular blood flow in normal-tension glaucoma are still not clear. Peripheral vascular disease seems to be associated with glaucoma populations independent of other cardiovascular risk factors. We found this presentation, for the first time, to our knowledge, as another probable vascular abnormality related to our patient with normal-tension glaucoma, although it is necessary to confirm its pathological effect in future studies. CASE PRESENTATION: Our patient was a 48-year-old Spanish man without any personal and family history of interest except for circulatory problems of the lower limbs with repetitive ulcers at the frontal and lateral aspects of his legs. His chief complaint was vision loss when he came to consult us. In exploration, his best corrected visual acuity was 20/20 in both eyes; initial intraocular pressure in the right eye was 14-16 mmHg and in the left eye was 16-18 mmHg, with a mild sclerosis of the lens in slit-lamp examination. No inflammation or pigmented lesion was detected in the anterior chamber. Open angle confirmed by Goldman four quadrants gonioscopy. Funduscopic examination revealed a vertical cup disc ratio of 0.6 in the right eye and 0.8 in the left eye. The patient's neuroretinal rim was normal in the right eye, and superior thinning in the left eye was determined. Examination of the patient's visual field showed inferior mild probable nasal scotoma in the right eye and an inferior deep arcuate scotoma defect in the left eye. His optical coherence tomography examination revealed thinning of the peripapillary nerve fiber layer thickness in the left eye and superior loss of macular retinal ganglion cells in the left eye. Normal intraocular pressure values were measured on the intraocular pressure curve without treatment (maximum value, 18-20 mmHg), discarding higher intraocular pressures measured out of office. Ultrasonic pachymetry measured 515/520 µm, and normal intraocular pressure measured with a PASCAL tonometer ruled out probable corneal biomechanical underestimations. The patient's polysomnography study was normal and excluded sleep apnea syndrome. The patient's serial mean blood pressure was normal, especially in the lower limbs (mean value, 125/70 mmHg), ruling out the possibility of systemic hypotension. Thyroidal and coagulation abnormalities, autoimmune disease, and inflammatory disease were excluded. Normal immunologic study and normal vascular biopsy were observed, as well as normal brain magnetic resonance imaging and a normal carotid vascular study. The primary diagnosis was moderate medium peripheral arterial disease in the lower limbs, which was confirmed by echography after ruling out other probable vascular abnormalities related to normal-tension glaucoma. CONCLUSION: After ruling out other systemic diseases and vascular abnormalities related to normal-tension glaucoma, we found peripheral arterial disease as a probable vascular abnormality related to normal-tension glaucoma in our patient. To our knowledge, this is the first time such a case has been reported. Thus, further research is needed to determine the relevance of these results to the general population.

The role of neuroinflammation in the pathogenesis of glaucoma neurodegeneration.

The chapter is a review enclosed in the volume "Glaucoma: A pancitopatia of the retina and beyond." No cure exists for glaucoma. Knowledge on the molecular and cellular alterations underlying glaucoma neurodegeneration (GL-ND) includes innovative and path-breaking research on neuroinflammation and neuroprotection. A series of events involving immune response (IR), oxidative stress and gene expression are occurring during the glaucoma course. Uveitic glaucoma (UG) is a prevalent acute/chronic complication, in the setting of chronic anterior chamber inflammation. Managing the disease requires a team approach to guarantee better results for eyes and vision. Advances in biomedicine/biotechnology are driving a tremendous revolution in ophthalmology and ophthalmic research. New diagnostic and imaging modalities, constantly refined, enable outstanding criteria for delimiting glaucomatous neurodegeneration. Moreover, biotherapies that may modulate or inhibit the IR must be considered among the first-line for glaucoma neuroprotection. This review offers the readers useful and practical information on the latest updates in this regard.

Cytokine expression in tears of patients with glaucoma or dry eye disease: A prospective, observational cohort study.

BACKGROUND: The aim of this study was to assess the expression of cytokines/chemokines in tears from patients with non-advanced primary open-angle glaucoma and patients with non-severe dry eye disease versus healthy controls. METHODS: This prospective, observational cohort study enrolled patients with confirmed or suspected non-advanced primary open-angle glaucoma who received any prostaglandin analogue monotherapy for longer than 6 months, patients with non-severe dry eye disease, and healthy controls. Expression of interleukin-1ß, interleukin-2, interleukin-4, interleukin-5, interleukin-6, interleukin-8, interleukin-10, and interleukin-12; tumor necrosis factor α; vascular endothelial growth factor; granulocyte-macrophage colony-stimulating factor; and interferon γ was assessed. RESULTS: 107 participants were enrolled (primary open-angle glaucoma, n = 41; dry eye disease, n = 30; and healthy controls, n = 36). Compared with healthy controls, interleukin-6 was significantly higher (p = 0.0001) in patients with primary open-angle glaucoma and interleukin-1ß (p = 0.0144), interleukin-6 (p < 0.0001), and interleukin-10 (p = 0.0392) were higher in patients with dry eye disease. Compared with patients with dry eye disease, patients with primary open-angle glaucoma had significantly lower levels of interleukin-4 (21.79 vs 20.18 pg/mL; p = 0.0012) and significantly higher levels of vascular endothelial growth factor (367.75 vs 609.28 pg/mL; p = 0.0058), tumor necrosis factor α (14.27 vs 17.93 pg/mL; p = 0.0048), and interleukin-6 (17.95 vs 27.48 pg/mL; p = 0.0145). In patients with primary open-angle glaucoma, interleukin-1ß expression (p = 0.0011) was lower than in those who received intraocular pressure-lowering eye drops without preservatives compared with those who received eye drops with preservatives. CONCLUSION: Different cytokine/chemokine expression profiles in tears of patients with primary open-angle glaucoma and dry eye disease strongly suggest the involvement of a variety of signaling pathways in the pathogenesis of these ophthalmic processes.

Current status of visual field examination in Andalusia, Spain: the SICVA Study.

PURPOSE: To ascertain the frequency of visual field examination (VFE) in patients attending public Andalusian hospitals (the SICVA study). METHODS: This was a multicenter, observational, retrospective study of patients with documented and/or suspected glaucoma subject to campimetric monitoring for longer than 2 years. The numbers of VFEs performed in the first 2 years and in the complete follow-up period were analyzed. Data on VFE reliability were studied and VFE change was collected based on the Glaucoma Staging System 2. RESULTS: A total of 722 eyes (from 467 consecutive patients), 349 with suspected and 373 with documented glaucoma, were included. Mean patient age was 65.9 years (SD = 11.3), and median follow-up time was 56 months (P25 = 36, P75 = 84). Three (P25 = 2, P75 = 4) VFEs were performed in the first 2 years of follow-up in the overall sample, as compared to 2 VFEs (P25 = 2, P75 = 4) in patients with suspected glaucoma, and 3 VFEs (P25 = 2, P75 = 4) in those with documented glaucoma (p<0.001). CONCLUSIONS: Based on these results, frequency of VFE in Andalusia differs from the standards recommended by the European Glaucoma Society to assess progression in the first 2 years of patient follow-up.

Patients undergoing long-term treatment with antihypertensive eye drops responded positively with respect to their ocular surface disorder to oral supplementation with antioxidants and essential fatty acids.

BACKGROUND: Glaucoma and dry eye disorders (DEDs) are frequent comorbidities. The antioxidant and anti-inflammatory properties of essential polyunsaturated fatty acids have been extensively studied in relation to eye diseases. OBJECTIVE: Our objective was to determine the effects of oral supplementation with a combined formulation of antioxidants and essential polyunsaturated fatty acids on expression of cytokines and chemokines in tears from patients with DEDs or primary open-angle glaucoma (POAG). METHODS: Participants (n = 97) were distributed into three groups: (1) individuals with nonsevere DEDs (DEDG), (2) individuals with nonadvanced POAG (POAGG), and (3) healthy controls. These groups were randomized into two subgroups: one received a daily antioxidant and essential polyunsaturated fatty acid supplement (two pills) for 3 months (+S), and the other did not (-NS). Participants were interviewed and ophthalmologically examined. Concentrations of specific cytokines and chemokines in reflex tears were determined by multiplexed particle-based flow cytometry. The data were analyzed statistically (SPSS version 15.0). RESULTS: Comparison of the results from the DEDG and POAGG patients showed significant differences in tear expression of granulocyte-macrophage colony-stimulating factor (P = 0.008), tumor necrosis factor α (P = 0.005), vascular endothelial growth factor (P = 0.038), interleukin-4 (P = 0.030), and interleukin-6 (P = 0.044). The main signs and symptoms of dry eyes such as dryness, burning, photophobia, eye heaviness, and blurred vision, as well as positive changes in eyelashes, hair, nails and skin, were significantly improved in DEDG +S and POAGG +S patients relative to unsupplemented patients. CONCLUSION: Inflammation biomarkers were differentially expressed in glaucomatous tears, but the differences changed upon antioxidant/essential polyunsaturated fatty acid supplementation. Chronic instillation of antihypertensive eye drops must be considered for integrating protocols to glaucoma standards of care.

Effects of a nutraceutical formulation based on the combination of antioxidants and ω-3 essential fatty acids in the expression of inflammation and immune response mediators in tears from patients with dry eye disorders.

BACKGROUND: Women, and those older than 65 years of age, are particularly susceptible to dry eye disorders (DEDs). Inflammation is clearly involved in the pathogenesis of DEDs, and there is mounting evidence on the antioxidant and antiinflammatory properties of essential polyunsaturated fatty acids (EPUFAs). OBJECTIVE: To analyze whether a combined formulation of antioxidants and long-chain EPUFAs may improve the evolution of DEDs. METHODS: We used a prospective study to address the relationship between risk factors, clinical outcomes, and expression levels of inflammation and immune response (IIR) mediators in human reflex tear samples. Participants included: (1) patients diagnosed with nonsevere DEDs (DED group [DEDG]); and (2) healthy controls (control group [CG]). Participants were randomly assigned to homogeneous subgroups according to daily oral intake (+S) or not (-NS) of antioxidants and long-chain EPUFAs for 3 months. After an interview and a systematized ophthalmic examination, reflex tears were collected simultaneously from both eyes; samples were later subjected to a multiplexed particle-based flow cytometry assay. A specific set of IIR mediators was analyzed. All data were statistically processed through the SPSS 15.0 software program. RESULTS: Significantly higher expressions of interleukin (IL)-1ß, IL6, and IL10 and significantly lower vascular endothelial growth factor expressions were found in the DEDG as compared to the CG. In the DEDG, significant negative correlations were detected between the Schirmer test and IL-1ß, IL6, IL8, and vascular endothelial growth factor levels, and between the fluorescein breakup time with IL6 and IL8 levels. However, levels of IL-1ß, IL6, and IL10 in tears were significantly lower in the DEDG+S versus the DEDG-NS and in the CG+S versus the CG-NS. Subjective symptoms of dry eye significantly improved in the DEDG+S versus the DEDG-NS. CONCLUSION: IIR mediators showed different expression patterns in DED patients, and these patterns changed in response to a combined formulation of antioxidant and EPUFAs supplementation. Our findings may be considered for future protocols integrating clinical/biochemical data to help manage DED patients.

Diagnostic capability of scanning laser polarimetry with and without enhanced corneal compensation and optical coherence tomography.

PURPOSE: To compare the abilities of the current commercially available versions of scanning laser polarimetry (SLP) and optical coherence tomography (OCT), SLP-variable corneal compensation (VCC), SLP-enhanced corneal compensation (ECC), and high-definition (HD) OCT, in discriminating between healthy eyes and those with early-to-moderate glaucomatous visual field loss. METHODS: Healthy volunteers and patients with glaucoma who met the eligibility criteria were consecutively enrolled in this prospective, cross-sectional, observational study. Subjects underwent complete eye examination, automated perimetry, SLP-ECC, SLP-VCC, and HD-OCT. Scanning laser polarimetry parameters were recalculated in 90-degree segments (quadrants) in the calculation circle to be compared. Areas under the receiver operating characteristic curve (AUROCs) were calculated for every parameter in order to compare the ability of each imaging modality to differentiate between normal and glaucomatous eyes. RESULTS: Fifty-five normal volunteers (mean age 59.1 years) and 33 patients with glaucoma (mean age 63.8 years) were enrolled. Average visual field mean deviation was -6.69 dB (95% confidence interval -8.07 to -5.31) in the glaucoma group. The largest AUROCs were associated with nerve fiber indicator (0.880 and 0.888) for the SLP-VCC and SLP-ECC, respectively, and with the average thickness in the HD-OCT (0.897). CONCLUSIONS: The best performing indices for the SLP-VCC, SLP-ECC, and HD OCT gave similar AUROCs, showing moderate diagnostic accuracy in patients with early to moderate glaucoma. Further studies are needed to evaluate the ability of these technologies to discriminate between normal and glaucomatous eyes.