[Ophthalmic agents during pregnancy]. / Ophthalmika in der Schwangerschaft.

The use of ophthalmic agents during pregnancy and breastfeeding always represents an off-label use. Therefore, the use of drugs must be particularly carefully assessed with respect to the risk-benefit assessment. In this overview the literature databank of the PubMed library, pharmaceutical lists (Red List, Swiss pharmaceutical compendium), guidelines of the specialist societies the German Society of Ophthalmology (DOG), the Swiss Society of Ophthalmology (SOG), the European Glaucoma Society (EGS), the American Academy of Ophthalmology (AAO) and internet portals (embryotox, reprotox) were inspected and recommendations for the use of ophthalmic agents during pregnancy and breastfeeding were derived. More attention should be dedicated to this topic in the specialist societies.

Cross-sectional study of intraocular cataract lens replacement, circadian rest-activity rhythms, and sleep quality in older adults.

STUDY OBJECTIVES: Age-related cataract decreases light transmission at the most sensitive spectrum for circadian photoentrainment, with negative ramifications for human health. Here, we assessed whether intraocular lens replacement (IOL) in older patients with previous cataract was associated with increased stability and amplitude of circadian rest-activity rhythms, and improved sleep quality. METHODS: Our cross-sectional study included sixteen healthy older individuals without ocular diseases (controls; 55-80 years; 63.6 ± 5.6y; 8 women) and 13 patients with previous cataract and bilateral IOL (eight with blue-blocking [BB] lens and five with ultraviolet-only [UV] blocking lens; 55-80 years; 69.9 ± 5.2y; 9 women). The study comprised three weeks of at home rest-activity assessments using wrist-worn actigraphs, and each week preceded a laboratory protocol. Primary outcomes were actigraphy-derived interdaily stability, intradaily variability, and relative amplitude of circadian rest-activity rhythms. Secondary outcomes were actigraphy-assessed sleep quality (i.e. time in bed, sleep duration, sleep efficiency, mean wake bout time and fragmentation index). RESULTS: Patients with IOL had significantly higher interdaily stability ("Group" effect: pFDR =.001), but not intradaily variability ("Group" effect: pFDR = n.s.), and significantly higher relative amplitude of rest-activity rhythms ("Group" effect: pFDR < .001). Moreover, patients with IOL had significantly higher activity levels during the day and lower levels during the evening, as compared to healthy older controls ("Group" effect: pFDR = .03). Analyses of actigraphy-derived sleep parameters yielded no significant differences across groups ("Group" effect: all pFDR > .1). CONCLUSIONS: Our cross-sectional study suggests that enhancing spectral lens transmission in patients with cataract may benefit their circadian health.

Intraocular cataract lens replacement and light exposure potentially impact procedural learning in older adults.

Procedural learning declines with age and appropriately timed light exposure can improve cognitive performance in older individuals. Because cataract reduces light transmission and is associated with cognitive decline in older adults, we explored whether lens replacement (intraocular blue-blocking [BB] or UV-only blocking) in older patients with cataracts enhances the beneficial effects of light on procedural learning. Healthy older participants (n = 16) and older patients with post-cataract surgery (n = 13 with BB or UV lens replacement) underwent a randomized within-subject crossover laboratory design with three protocols. In each protocol, 3.5 hr dim-dark adaptation was followed by 2 hr evening blue-enriched (6,500K) or non-blue-enriched light exposure (3,000K or 2,500K), 30 min dim post-light, ~8 hr sleep and 2 hr morning dim light. Procedural learning was assessed by the alternating serial reaction time task (ASRT), as part of a larger test battery. Here, ASRT performance was indexed by type of trial (random or sequence) and sequence-specific (high or low probability) measures. During evening light exposure, we observed a significant effect of the interaction of "group" versus "light condition" on the type of trial (p = .04; p = .16; unadjusted and adjusted p-values, respectively) and sequence-specific learning (p = .04; p = .16; unadjusted and adjusted p-values, respectively), whereby patients with UV lens replacement performed better than patients with BB lens or non-cataract controls, during blue-enriched light exposure. Lens replacement in patients with cataracts may potentially be associated with beneficial effects of blue light on procedural learning. Thus, optimizing spectral lens transmission in patients with cataracts may help improve specific aspects of cognitive function, such as procedural learning.

Association of Intraocular Cataract Lens Replacement With Circadian Rhythms, Cognitive Function, and Sleep in Older Adults.

IMPORTANCE: Cataract is associated with a progressive decline in light transmission due to the clouding and yellowing of the natural crystalline lens. While the downstream effects of aging lenses include long-term disruption of circadian rhythms, cognitive function, and sleep regulation, it remains unknown whether there is an association of intraocular cataract lens (IOLs) replacement with circadian rhythms, cognition, and sleep. OBJECTIVE: To test whether IOL replacement (blue blocking [BB] or ultraviolet [UV] only blocking) in older patients with previous cataract is associated with the beneficial light effects on the circadian system, cognition, and sleep regulation. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study at the Centre for Chronobiology, University of Basel in Switzerland from February 2012 to April 2014, analyzed between June 2012 and September 2018. Sixteen healthy older controls and 13 patients with previous cataract and IOL replacement participated without medication and no medical and sleep comorbidities. EXPOSURES: Three and a half hours of prior light control (dim-dark adaptation), followed by 2 hours of evening blue-enriched (6500 K) or non-blue-enriched light exposure (3000 K and 2500 K), 30 minutes in dim post-light exposure, 8 hours of sleep opportunity, and 2 hours of morning dim light following sleep. MAIN OUTCOMES AND MEASURES: Salivary melatonin, cognitive tests, and sleep structure and electroencephalographic activity to test the association of IOLs with markers of circadian rhythmicity, cognitive performance, and sleep regulation, respectively. RESULTS: The participants included 16 healthy older controls with a mean (standard error of the mean [SEM]) of 63.6 (5.6) years; 8 women and 13 patients with previous cataract (mean [SEM] age, 69.9 [5.2] years; 10 women); 5 patients had UV IOLs and 8 had BB IOLs. Patients with previous cataract and IOLs had an attenuated increase in melatonin levels during light exposure (mean [SEM] increase in the BB group: 23.3% [2.6%] and in the UV lens group: 19.1% [2.1%]) than controls (mean [SEM] increase, 48.8% [5.2%]) (difference between means, 27.7; 95% CI, 15.4%-41.7%; P < .001). Cognitive function, indexed by sustained attention performance, was improved in patients with UV lens (mean [SEM], 276.9 [11.1] milliseconds) compared with patients with BB lens (mean [SEM], 348.3 [17.8] milliseconds) (difference between means, 71.4; 95% CI, 29.5%-113.1%; P = .002) during light exposure and in the morning after sleep. Patients with UV lens had increased slow-wave sleep (mean [SEM] increase, 13% [3.4%]) compared with controls (mean [SEM] increase, 5.2% [0.8%]) (percentage of total sleep time; difference between means, 7.9; 95% CI, 2.4%-13.4%; P = .02) and frontal non-rapid eye movement slow-wave activity (0.75-4.5 Hz) during the first sleep cycle (mean [SEM], 79.9 [13.6] µV2/Hz) compared with patients with BB lens (mean [SEM], 53.2 [10.7] µV2/Hz) (difference between means, 26.7; 95% CI, 9.2-48.9; P = .03). CONCLUSIONS AND RELEVANCE: These in-laboratory empirical findings suggest that optimizing the spectral lens transmission in patients with previous cataract may minimize the adverse age-related effects on circadian rhythms, cognition, and sleep.

Evaluation of Visual Comfort and Mental Effort Under Different Light Conditions for Ultraviolet-Absorbing and Additional Blue-Filtering Intraocular Lenses for Cataract Surgery.

PATIENTS AND METHODS: Patients with an ultraviolet blocking lens (UV) (n = 5) or blue filter lens (BB) (n = 8) after intraocular lens (IOL) replacement for cataract and age-adjusted controls (AACs) (n = 16) underwent a balanced crossover within-subject design. After 1.5 h of dark adaptation, they were exposed to polychromatic light at 6500 K (blue-enriched) and 2500 K and 3000 K (non-blue-enriched) for 2 hours in the evening. Visual comfort and mental effort were repeatedly assessed by the Visual Analogue Scale (0 - 100) and the Visual Comfort and Mental Effort Rating Scale (0 - 100) for each light condition. The results were compared using mixed model analysis. RESULTS: The mean (± SD) age for AAC and patients with UV or BB was 69.8 ± 6.2 y, 70.8 ± 4 y, and 63.6 ± 5.6 y, respectively. Irrespective of the light condition, patients with UV and BB felt mentally more tired during the experiments compared to AACs (F = 6.15, p = 0.003). However, patients with BB were mentally more motivated to perform the exercises compared to patients with UV and AACs (F = 8.1, p < 0.001). Patients with BB perceived ambient light as less glary (F = 4.71, p = 0.01) than patients with UV. Blue ambient light was felt less intensely in patients with BB (F = 2.51, p = 0.042) compared to those with UV and the AACs. CONCLUSION: Lens replacement in older cataract patients may increase visual comfort and minimize mental effort. While subtle, the magnitude of these effects may depend on the type of intraocular lens. BB intraocular lenses may have potential benefits, as ambient light is perceived as having less glare and less visual tension.

OCT Angiography of the Central Macular Capillary Network in Glaucoma Patients and Healthy Controls.

PURPOSE: We aimed to investigate central macular microvasculature by optical coherence tomography angiography (OCTA) and to analyse its relation to alterations in classical parameters of optical coherence tomography (OCT) in glaucoma patients. METHODS: Using OCTA (Avanti incl. AngioVue; Optovue, Inc., Fremont, CA), the superficial flow (SF) and the superficial non-flow (SNF) area of the macula, as well as the S-ETDRS (based on Early Treatment Diabetic Retinopathy charts). and S-grid vessel density (zones 1 - 9) of the macula, were evaluated in 27 glaucoma patients (49 eyes) and compared to those of 27 age-matched healthy controls (50 eyes; p = 0.253). The interactions between OCTA parameters representing macular microvasculature and classical OCT measurements of the circumpapillary retinal nerve fibre layer (RNFL) and macular ganglion cells (mGCC) were analysed within groups (linear mixed-effects model). RESULTS: SF, SNF, and S-ETDRS vessel density exhibited no significant difference between the glaucoma and control groups (all p ≥ 0.158). However, within the glaucoma group, decreased RNFL and mGCC thickness correlated significantly with decreased S-ETDRS density (zones 1; 2 - 9, p ≤ 0.033). The same held true for the interactions between the RNFL and mGCC thickness with S-grid density (zones 1 - 3; 6 - 9; p ≤ 0.033). For perimetric glaucoma patients, subgroup analyses demonstrated significantly reduced density maps of superficial foveal flow as well as significant interactions between OCT and OCTA parameters; this was not the case within the preperimetric group. CONCLUSIONS: Even if the central macular microvasculature, as measured by SF and SNF, is found preserved in glaucoma, the strong positive relation between the central microvascular and structural changes in OCTA and OCT indicates that there are alterations in central macular microvasculature in subclinical glaucoma.

[The Impact of Multiple Intravitreal Anti-VEGF Injections on Intraocular Pressure]. / Der Einfluss multipler Anti-VEGF-Injektionen auf den intraokularen Druck.

BACKGROUND: To evaluate the possible effects of multiple intravitreal anti-vascular endothelial growth factor (VEGF) injections on intraocular pressure (IOP). METHODS: This study included 50 eyes of 50 patients who underwent multiple (≥ 10 injections) intravitreal anti-VEGF injections in one eye with age-related macular degeneration, diabetic macular edema or retinal vein occlusion. IOP was recorded after every injection on the first postoperative day. IOP > 21 mmHg was regarded as abnormal. For statistical analysis, the IOP was correlated with the number of injections. RESULTS: A total of 669 IOP-measurements (mean 13.4 treatment/eye) were analyzed. No IOP-elevation was recorded in 43 eyes (86%). Transient elevated IOP > 21 mmHg was measured after 19 intravitreal injections (2.8%, one patients with 8 IOP elevations). In general, there was no increasing risk of IOP elevation with time, no case of sustained IOP elevation and no additional long term glaucoma treatment necessary. Eyes with pre-existing glaucoma were significantly more affected from transient IOP-elevation than non-glaucoma eyes (5.5 vs. 2.2%). CONCLUSIONS: Multiple anti-VEGF injections are not associated with an increased risk of sustained IOP-elevation. On the other hand, individual risk factors exist and predispose to IOP-elevation (e.g., pre-existing glaucoma).

[Status of Selective Laser Trabeculoplasty (SLT)]. / Stellenwert der selektiven Lasertrabekuloplastik (SLT).

Purpose Worldwide, in recent years, selective laser trabeculoplasty (SLT) has developed into a very successful therapy for glaucoma. Material and Methods The article provides a review of the literature from PubMed and clinical experience. Results SLT is equally efficacious to argon laser trabeculoplasty (ALT) and to a first-line glaucoma medication. SLT can be used in most common forms of open-angle glaucoma and ocular hypertension. In contrast to ALT, SLT is repeatable and requires much less energy. SLT has been reported to be also successful in some rare forms of ocular hypertension/glaucoma. There is no negative influence of SLT to other forms of glaucoma treatment. Complications are rare and include intraocular pressure spikes, corneal scarring or corneal decompensation due to endothelial cell damage and cystoid macular edema. The potential of SLT as a first-line treatment of glaucoma is now under investigation. Conclusion SLT is a low-risk procedure to treat glaucoma in a broad range of indications. Advantages of SLT include the potential to use SLT more and more as a primary treatment procedure. Therefore, SLT is now under intensive investigation worldwide.

Multifocal corneal ablation (Supracor) in hyperopic presbyopia: 1-year results in a cross-sectional study.

PURPOSE: To evaluate the efficacy and safety of the multifocal excimer laser corneal ablation profile (the Supracor procedure) in hyperopic presbyopia 1 year after laser treatment. METHODS: This prospective, consecutive, one-center, cross-sectional study included 20 patients with hyperopic presbyopia 1 year after treatment with the Supracor procedure. The main outcome measures were monocular uncorrected distance visual acuity (UDVA) and uncorrected near visual acuity (UNVA), photopic contrast sensitivity (Pelli-Robson charts), patient satisfaction, and functioning at 12 months. RESULTS: Thirty-nine eyes of 20 patients (mean age 59 ± 7.2 years) were treated. Mean UDVA improved from 0.56 ± 0.31 (mean 0.34 logMAR) preoperatively to 0.9 ± 0.15 (mean 0.06 logMAR) 12 months after surgery. Mean UNVA increased from 0.15 ± 0.07 (mean 0.84 logMAR) before surgery to 0.62 ± 0.24 (mean 0.23 logMAR) 12 months after treatment. Four eyes lost 2 lines of corrected distance visual acuity (10.3%). Monocular photopic contrast sensitivity was within age-correlated normal range (Pelli-Robson chart, mean contrast sensitivity 1.83 ± 0.18). A total of 75% of the patients would undergo Supracor again (1 not, 4 perhaps). The most frequently reported side effects were increased glare, reduced distance vision, and fluctuations in vision. Most patients used artificial tears. CONCLUSIONS: One year after Supracor, UDVA and UNVA improved markedly, photopic contrast sensitivity was in normal age-correlated range, and the majority of patients (75%) was satisfied with the results. Side effects like loss of distance vision, fluctuations of vision, and increased glare have a greater influence on patient satisfaction than the improvement of spectacle-free near vision.

Selective laser trabeculoplasty (SLT): 1-year results in early and advanced open angle glaucoma.

The purpose of this study was to examine the efficacy of selective laser trabeculoplasty (SLT) in eyes with early and more advanced stages of open angle glaucoma within 1 year of follow-up. Retrospective chart review in a consecutive series of patients treated by SLT to reduce intraocular pressure (IOP) or decrease number of topical medications in cases of discomfort and allergy. The cup-to-disc ratio of the optic nerve and the GSS 2 (glaucoma staging system 2) was used to differentiate between early (group 1) and more advanced (group 2) stages of glaucoma. At the time of SLT treatment, no new signs of glaucoma progression were seen. Only the first treated eye of every patient was included in the analysis. In group 1 (early glaucoma), 27 eyes were included. IOP reduction <21 mmHg/>20 % of the preoperative IOP-value and reduction of medication were achieved in 17 eyes (62.96 %). Successful re-treatment was necessary in 2 eyes (7.4 %). In group 2 (advanced glaucoma), 44 eyes underwent SLT. In eight eyes (18.18 %), filtrating surgery was necessary after initial SLT. In the remaining 36 eyes, IOP reduction <21 mmHg/>20 % of the baseline IOP was achieved in 26 eyes (59.09 % of 44 eyes) and IOP reduction <18 mmHg/> 30 % of the baseline IOP in 22 eyes (50 % of 44 eyes). SLT was safe and effective in nearly 2/3 of early glaucoma patients and also in 50 % of advanced glaucoma patients using stronger criteria of success. Failure of SLT in advanced glaucoma should lead to immediate filtrating surgery, which seems not to be associated with higher risk of fibrosis.

Association of ocular hypotensive medication types with dynamic contour tonometry and Goldmann applanation tonometry measurements in a glaucoma and ocular hypertensive population.

PURPOSE: The aim of this study was to evaluate the association between different intraocular pressure (IOP)-lowering medications and IOP measurements by dynamic contour tonometry (DCT) and Goldmann applanation tonometry (GAT) in a glaucoma and ocular hypertensive population. METHODS: In a prospective, observational case series study, 410 eyes from 410 consecutive patients with open-angle glaucoma (OAG) or ocular hypertension (OHT), were enrolled. All eyes included in the study received unaltered ocular hypotensive medication for at least 6 months before IOP measurement. All eyes underwent 2 GAT and 3 DCT measurements, and their means were used for the analysis. RESULTS: DCT-GAT IOP difference (ΔIOP) did not differ statistically significantly (P=0.49) between OAG and OHT group yielding a mean±SD of 4.26±2.02 mmHg and 4.41±2.25 mmHg, respectively. The number of IOP-lowering agents did not have any statistically significant influence on ΔIOP (p=0.177), DCT (P=0.28) and GAT (P=0.13) measurements. A statistically higher ΔIOP was revealed in monotherapy patients receiving Carbonic Anhydrase Inhibitors (CAIs) (ΔIOP=5.75 mmHg) in comparison to patients receiving Prostaglandin Analogs (ΔIOP=4.09 mm Hg) or beta Blockers (ΔIOP=3.78 mmHg) as single topical therapy (F=4.373, P=0.005). Eyes treated with CAIs as a part of the ocular hypotensive therapy yielded a significantly greater ΔIOP (P=0.0035) than those without CAIs in the therapeutic schema. CONCLUSIONS: The difference between DCT and GAT IOP measurements is found to be statistically significantly higher in patients receiving CAIs either as monotherapy or as a part of a combined ocular hypotensive treatment, while DCT and GAT readings remain unaffected. The type of diagnosis and the number of ocular hypotensive medications had no statistically significant influence on ΔIOP.

Serotonin (5-HT7) receptor-stimulated activation of cAMP-PKA pathway in bovine corneal epithelial and endothelial cells.

BACKGROUND: 5-Hydroxytryptamine (5-HT; serotonin) is a major neurotransmitter, and its receptors are found throughout the whole body. The 5-HT7 receptor subtype was detected in human corneal epithelial and endothelial cells and found to be functionally active in a corneal epithelial cell line. The aim of the present study was to demonstrate that native bovine corneal epithelial and endothelial cells express a functional 5-HT7 receptor positively coupled to adenylyl cyclase and protein kinase A (PKA) formation. METHODS: 5-HT7 receptors were studied using polyclonal antibodies. cAMP concentration after 5-HT7 receptor stimulation with 5-carboxamidotryptamine (5-CT, a 5-HT7 agonist) was tested by enzyme immunoassay, PKA activity was estimated by kinase consumption of ATP. RESULTS: Immunocytochemistry and immunofluorescence revealed the presence of 5-HT7 receptors in corneal epithelial and endothelial cells. Stimulation of corneal 5-HT7 receptors with 5-CT revealed a dose-dependent increase in intracellular cAMP concentration in corneal epithelium (0.01-0.34 pmol/ml) and endothelium (0.01-0.19 pmol/ml) between 10(-10) and 10(-7) mg/ml 5-CT (p = 0.001) with maximal stimulation from 10(-7) to 10(-3) mg/ml 5-CT (0.30 ± 0.03 and 0.18 ± 0.01 pmol/ml, respectively). Incubation with 10(-6) mg/ml SB269970 (a selective 5-HT7 antagonist) blocked 5-CT-induced cAMP increase in corneal epithelial (0.03 pmol/ml) and endothelial cells (0.02 pmol/ml; p = 0.001). Stimulation of corneal 5-HT7 receptors with 5-CT revealed a dose-dependent increase in PKA activity between 10(-10) and 10(-8) mg/ml 5-CT in corneal epithelium and endothelium (<1 to >99%; p = 0.013 and p = 0.017, respectively) with maximal stimulation from 10(-8) to 10(-4) mg/ml (>99%) 5-CT. CONCLUSIONS: Our data demonstrate that native corneal epithelial and endothelial cells express a functional 5-HT7 receptor positively coupled to adenylyl cyclase and PKA formation. However, at the present time, the physiological role of 5-HT receptors and the cAMP-PKA pathway in the cornea remains a matter of speculation.

Decreased ocular pulse amplitude associated with functional and structural damage in open-angle glaucoma.

PURPOSE: To assess the relationship of ocular pulse amplitude (OPA), as measured by dynamic contour tonometry (DCT), with structural and functional damage in patients with open-angle glaucoma (OAG). METHODS: In this cross-sectional, observational study, 242 eyes of 139 patients with OAG underwent Goldmann applanation tonometry (GAT), DCT, central corneal thickness (CCT) measurement, visual fields examination (Octopus, Haag Streit), and complete ophthalmologic examination. Linear regression analysis was used to analyze the effect of OPA, DCT, GAT, and CCT to the mean defect (MD) of the visual fields and to the vertical cup to disc ratio (CDR). RESULTS: Ocular pulse amplitude was the only variable that showed a significant association with MD (slope=-1.1, p=0.012), in contrast to GAT (p=0.98), DCT (p=0.32), and CCT (p=0.42). Ocular pulse amplitude was also negatively associated with CDR (slope=-0.028, p=0.0001). Additional multiple regression analysis revealed that OPA (R2=0.12, r=-0.25, slope=-0.02, p=0.033), GAT (r=-0.27, slope=-0.01, p=0.027), and CCT (r=-0.18, slope=-0.001, p=0.012) were statistically significantly correlated to CDR, while DCT was not (r=-0.20, slope=0.003, p=0.46). Ocular pulse amplitude did not differ statistically significantly (p=0.93) between eyes with (2.79 ± 1.42) and without (2.77 ± 1.21) prior trabeculectomy. No statistically significant difference of OPA was observed between diagnosis groups (p=0.255). CONCLUSIONS: Decreased OPA seems to be correlated with increased glaucomatous functional and structural damage in OAG. Assessment of OPA by DCT could therefore serve as an important additional parameter in the evaluation of glaucoma patients.