The use of HCT and/or ACE inhibitors significantly increases the risk of non-melanotic skin cancer in the periocular region.

BACKGROUND/AIMS: To investigate a possible association between the use of hydrochlorothiazide (HCT) and/or angiotensin-converting enzyme inhibitors (ACE inhibitors) and the occurrence of periocular non-melanoma skin cancer. METHODS: The files of 929 patients from the University Medical Center Hamburg-Eppendorf who were surgically treated for suspected periocular malignancy were evaluated retrospectively regarding the occurrence of non-melanoma skin cancer and concomitant medication. To be able to put the data in an overall context, we also analyzed age-matched routine data of the DAK-Gesundheit (DAK-G), a nationwide operating German health insurance company. RESULTS: Of the 929 patient records examined, who underwent surgical excision for suspected non-melanotic malignancy, non-melanocytic skin cancer could actually be determined by histology in 199 patients. In total, 176 patients (103 women, 72 men) had a basal cell carcinoma and 23 patients (16 women, 7 men) suffered from squamous cell carcinoma. The rate of intake of HCT or ACE inhibitors in our patient collective with non-melanotic skin cancer is significantly higher than in the general age-matched population (ORACE: 2.51, p < 0.001; ORHCT: 7.24, p < 0.001, ORBOTH: 4.61, p < 0.001). CONCLUSION: The rate of intake of HCT or ACE inhibitors is significantly higher in our patient collective with non-melanotic skin cancer compared to the group from the age-matched general population (DAK insured (p < 0.001)) compared to the routine data of the DAK-G. This leads us to the conclusion that taking the medication is associated with an increased risk for non-melanotic skin cancer. We recommend regular skin cancer screening, moderate ordination of photosensitizing medication, but above all comprehensive clarification of possible risks.

[Comparative analysis of refractive and topographic changes after eyelid surgery]. / Vergleichende Analyse der Refraktions- und Topographieveränderungen nach lidchirurgischen Eingriffen.

BACKGROUND: There is largely a lack of clarity on the question of whether refraction or topography changes are to be expected after blepharoplasty, levator resection, or a lateral tarsal strip procedure. MATERIALS AND METHODS: Therefore, in the present study, objective refraction, anterior eye segment tomography, and visual acuity tests were carried out pre- and postoperatively in 78 patients and then analyzed. The examination was carried out preoperatively, at suture removal after 10 days, and after 3 months. RESULTS: Neither after blepharoplasty nor after a lateral tarsal strip procedure were significant changes in vision or refraction seen in the topography. In contrast, the Wilcoxon sign test 10 days after levator resection showed a significant increase in the cylinder after 10 days compared to the preoperative level (p = 0.042). However, this change was no longer detectable after 3 months. CONCLUSION: The authors postulate that extensive patient education with regard to temporary visual changes, particularly in the case of levator resections, is essential and that additional refraction and topography control can be useful postoperatively.

[Comparison of subjective improvement in quality of life of patients after open and minimally invasive surgical techniques for recanalization of lacrimal duct stenosis in 2015-2018]. / Vergleich der subjektiven Lebensqualitätsverbesserung von Patienten nach eröffnenden und minimal-invasiven Operationstechniken zur Rekanalisierung von Tränenwegsstenosen in den Jahren 2015 bis 2018.

BACKGROUND: Open and minimally invasive tear duct surgery are among the common surgical indications; however, little is known so far about the respective influences on the quality of life. OBJECTIVE: The aim of this study was to compare the subjective influence on the quality of life of patients after open and minimally invasive surgical techniques for recanalization of dacryostenosis. MATERIAL AND METHODS: From the collective of patients who were surgically treated at the University Medical Center Hamburg-Eppendorf from 2015 to 2018, a total of 169 patients (111 dacryocystorhinostomy, DCR, 58 endoscopy) took part in the survey and answered 9 questions about subjective satisfaction, which were evaluated also comparatively. RESULTS: When asked about postoperative satisfaction, the patients were significantly more satisfied after DCR (p = 0.001) than the patients who underwent a lacrimal endoscopy. There was no significant difference in terms of postoperative complications (p = 0.348). The rate of reoperations, however, was significantly higher in the patient group who underwent lacrimal endoscopy (χ2-test, p = 0.004). CONCLUSION: In summary it can be said that DCR is not inferior to lacrimal endoscopy in terms of patient satisfaction.

[Comparative analysis of refractive and topographic changes after eye muscle surgery]. / Vergleichende Analyse der Refraktions- und Topographieveränderungen nach Augenmuskeloperationen.

BACKGROUND: The question of whether refractive or topographic changes are to be expected after eye muscle surgery is largely unanswered. MATERIALS AND METHODS: Results of pre- and postoperative objective refraction, Pentacam (Oculus, Menlo Park, CA, USA), and visual acuity tests of 229 eyes are included in the present analysis. The examinations took place preoperatively, on the first postoperative day, and after 3 months. RESULTS: After surgery on one or two extraocular recti muscle, there are significant changes in the cylinder (p < 0.001) on the first postoperative day, although values returned to normal after 3 months. Similar changes also appeared in combined operations of extraocular and oblique muscles. CONCLUSION: The authors postulate that extensive patient education with regard to temporary changes in the cylinder is necessary, particularly when the extraocular muscles are involved, and that additional refraction and topography control can be useful postoperatively if visual rehabilitation is inadequate.

[Treatment of postoperative endophthalmitis : Operate or only inject?] / Therapie der postoperativen Endophthalmitis : Operieren oder nur injizieren?

BACKGROUND: Postoperative endophthalmitis is among the most feared complications encountered after intraocular surgery. A prompt diagnosis and initiation of treatment are crucial for the visual prognosis, which also depends on the causative microorganism. Despite advances in prevention and the availability of more epidemiological data, most of the evidence for treatment dates back to a single study, the early vitrectomy study (EVS) carried out in the early 1990s. The EVS showed that vitrectomy with intravitreal antibiotics was superior to intravitreal antibiotics alone, only when visual acuity was light perception or below. The addition of systemic antibiotics did not have any benefits. Over the last 30 years, however, surgical techniques have continued to evolve and the medicinal options have also been expanded. Moreover, the EVS examined only endophthalmitis after cataract surgery and strictly speaking the results cannot be transferred to endophthalmitis from other causes. OBJECTIVE: This review discusses the current evidence for the different treatment modalities of the most important types of postoperative endophthalmitis. CONCLUSION: The EVS provided important guidelines for the initial management of endophthalmitis and these guidelines remain relevant to this day; however, in view of the refinement of surgical techniques, novel treatment options, especially the nowadays continuously growing number of intravitreal injections and even some new antibiotics, it would be desirable if new controlled trials addressing the treatment of endophthalmitis would be performed.

[Treatment of retinal detachment during the COVID-19 pandemic : Did patients with retinal detachment seek treatment later during the COVID-19 pandemic? Results from a German university eye hospital]. / Amotio-retinae-Versorgung während der Corona-Pandemie : Suchten Patienten mit Netzhautablösung während der Corona-Pandemie später den Augenarzt auf? Ergebnisse aus einer deutschen Universitätsaugenklinik.

BACKGROUND: Retinal detachment is an ophthalmological emergency. Delayed diagnostics and treatment increase the risk of permanent loss of vision. Current media reports have suggested that patients with medical emergencies delay seeking treatment out of fear of being infected with the corona virus SARS-CoV­2. This study analyzed data from a German university hospital to determine if the coronavirus pandemic had an impact on treatment and visual outcomes of patients with retinal detachment. METHODS: In this study 60 patients treated for rhegmatogenous retinal detachment in the eye hospital of the University Hospital Hamburg-Eppendorf between 15 March and 5 May 2020 were retrospectively analyzed. Patients from the corresponding period of the previous year acted as a control group. Significant differences between the groups were investigated by hypothesis testing. RESULTS: When compared to the period in the previous year there were no significant differences for sex, age, eye, length of symptoms, previous visit to doctor, visual acuity, macula status, degree of retinal detachment, proliferative vitreoretinopathy and type or length of procedure during the coronavirus pandemic. Of the patients with retinal detachment 29% had general health concerns due to the coronavirus pandemic. CONCLUSION: Medical treatment for retinal detachment was not influenced by the coronavirus pandemic. In contrast to other medical emergencies the morbidity of retinal detachment did not increase and admitted cases did not decrease during the pandemic when compared to the same period in the previous year.

Metabolomics as read-across tool: An example with 3-aminopropanol and 2-aminoethanol.

Read-across and grouping is one of the most commonly used alternative approaches for data gap filling in registrations submitted under the REACH Regulation as defined by the European Chemicals Agency (ECHA) in their 'Read-Across Assessment Framework' (RAAF, 2017). At the same time, the application of read-across is rejected by ECHA frequently due to various reasons. As a major reason hereof, applicants fail to reduce the level of 'remaining uncertainty' intrinsical to every read-across approach compared to testing a substance experimentally. Recently, the use of metabolomics to support read-across cases with biological information has been reported in a case study with phenoxy herbicides (Ravenzwaay et al., 2016). In the present case-study a 'weight-of-evidence' read-across approach from 2-aminoethanol (MEA = 'source') to 3-aminopropanol (3AP = 'target') with metabolomics as 'supporting evidence' reducing the remaining uncertainties is reported. We demonstrate the high structural similarity of the two analogous substances based on the available data and we report how metabolome data add confidence concerning mechanistic similarity in this read-across approach. Finally, the herein described read-across case supported by metabolomics is used to cover the data gaps in repeated dose and reproductive toxicity endpoint of 3AP via weight of evidence for the REACH-registration.

[Picosecond infrared laser fiber-assisted sclerostomy (PIRL-FAST) : A first proof of principle analysis]. / Pikosekundenlaser-Faser-assistierte Sklerostomie (PIRL-FAST) : Ein erster Machbarkeitsnachweis.

INTRODUCTION: The aim of this study was an analysis of the feasibility of a picosecond infrared laser fiber-assisted sclerostomy (PIRL-FAST) using a novel sapphire fiber and different energy levels of the picosecond laser. METHOD: The laser-assisted sclerostomy was carried out with a newly generated sapphire fiber of the PIRL-HP2-1064 OPA-3000 (Attodyne, Canada). Immediately after the intervention, the eyes were fixed in phosphate-buffered 3.5% formaldehyde. For subsequent histological analysis the eyes were cut into 4 µm thick sections and stained with hematoxylin and eosin (H&E, Merck, Darmstadt, Germany). All preparations were then scanned and digitalized using the MIRAX SCAN (Carl Zeiss Microimaging GmbH, Jena, Germany). RESULTS: The pulse energies 150 µJ (N = 4), 175 µJ (N = 6), 200 µJ (N = 7) and 250 µJ (N = 6) were selected. Within the framework of this first feasibility analysis 400 µm (10 sequential sections) of the sclerotomies were evaluated. The mean area of PIRL-FAST showed a dependency on the pulse energy applied. The diameter of the collateral damage zone (CDZ) depended on the pulse energy used. The largest CDZ could be measured using the highest pulse energy in this experiment (250 µJ). The environmental scanning electron microscope (ESEM) results revealed circular smooth sclerostomy wall with only minimal change of tissue ultrastructure. CONCLUSION: The PIRL-FAST using sapphire fibers is a new minimally invasive instrument to provide robust stenting from the anterior chamber to the subconjunctival space. Since the PIRL has proven to work efficiently in sectioning several tissues with minimal collateral damage these first proof of principle experiments might pave the way for a new minimally invasive glaucoma surgery strategy. We have already initiated experiments to analyze the wound healing and scar formation in vivo.

[Novel vitreous body replacement with hydrogel?] / Neuer Glaskörperersatz mit Hydrogel?

Although the surgical treatment of rhegmatogenous retinal detachment has advanced, there still is a significant risk of redetachment and a slow visual rehabilitation due to the use of endotamponades. Hydrophobic tamponades act via a buoyancy vector causing an accumulation of proinflammatory cytokines opposite the buoyancy vector. So far, the use of hydrophilic endotamponades is very promising because they represent a possible solution for the abovementioned problems of surgical ablation. This article presents the current developments in this field.

[Nanoparticles as drug delivery systems in ophthalmology]. / Nanopartikel als Drug-Delivery-Systeme für die Ophthalmologie.

Nanoparticles are perfectly suited as drug delivery systems due to their size and the diversity of materials used. They are able to penetrate biological barriers, can directly deliver drugs to the target site and provide a sustained release profile. Having long been established in oncology, in the last decade research has started to take a closer look at the potential of nanoparticles for ocular drug delivery. Obstacles, such as poor delivery of drugs via eye drops and the side effects of invasive methods, such as placing implants as drug depots could be overcome. Among the most relevant investigated structures are polymeric nanoparticles, micelles, liposomes, solid lipid nanoparticles, dendrimers and cyclodextrins. Besides the composition of the nanoparticle itself, its efficacy and stability can be optimized through coatings; however, long-term stability, standardization of production and toxicity remain the major challenges. The preclinical and partly clinical results obtained so far will hopefully give impulse to the idea of applying nanoparticles for optimized ocular drug delivery in the near future.

Establishment of a retinal hypoxia organ culture model.

Hypoxia plays an important role in several retinal diseases, especially in central retinal artery occlusion (CRAO). Although CRAO has been known for over a hundred years, no cure or sufficient treatment is available. Potential therapies are being evaluated in several in vivo models or primary cultures. However, in vivo models or primary cultures are very time-consuming, expensive, and furthermore several therapies or agents cannot be tested. Therefore, we aimed to develop a standardized organotypic ex vivo retinal hypoxia model. A chamber was developed in which rat retinal explants were incubated for different hypoxia durations. Afterwards, the retinas were adjusted to normal air and incubated for 24, 48 or 72 h under standard conditions. To analyze the retinal explants, and in particular the retinal ganglion cells (RGC) immunohistology, western blot and optical coherence tomography (OCT) measurements were performed. To compare our model to a standardized degeneration model, additional retinal explants were treated with 0.5 and 1 mM glutamate. Depending on hypoxia duration and incubation time, the amount of RGCs decreased and accordingly, the amount of TUNEL-positive RGCs increased. Furthermore, ß-III-tubulin expression and retinal thickness significantly decreased with longer-lasting hypoxia. The reduction of RGCs induced by 75 min of hypoxia was comparable to the one of 1 mM glutamate treatment after 24 h (20.27% versus 19.69%) and 48 h (13.41% versus 14.41%) of incubation. We successfully established a cheap, standardized, easy-to-use organotypic culture model for retinal hypoxia. We selected 75 min of hypoxia for further studies, as approximately 50% of the RGC died compared to the control group after 48 h.

Metabolomics as read-across tool: A case study with phenoxy herbicides.

New technologies, such as metabolomics, can address chemical grouping and read across from a biological perspective. In a virtual case study, we selected MCPP as target substance and MCPA and 2,4-DP as source substances with the goal to waive a 90-day study with MCPP. In order to develop a convincing case to show how biological data can substantiate read across, we used metabolomics on blood samples from the 28-day studies to show the qualitative and quantitative similarity of the substances. The 28-day metabolome evaluation of source substances and the target substance indicate liver and kidneys as target organs. 2,4-DP was identified as the best source substance. Using the information of the 90-day 2,4-DP study, we predicted MCPP's toxicity profile at 2500 ppm: reduced food consumption and body weight gain, liver and kidney weight increases with clinical-pathology changes and a moderate red blood cell parameter reduction. NOEL prediction for MCPP was below that of 2,4-DP (<500 ppm), and similar to that of MCPA (≥150 ppm). Qualitatively, these predictions are comparable to the results of the real MCPP 90-day study in rats (reduced food consumption and body weight gain, weight increases and clinical-pathology changes in liver and kidneys, reduced red blood cells values). Quantitatively, the predicted NOAEL (150 ppm) is similar to the actual study (NOEL = 75 ppm, NOAEL ≤ 500 ppm). Thus, the 90-day rat toxicity study of MCPP could have been waived and substituted by the 90-day results of 2,4-DP by using metabolome data of 28 day studies.

Metabolite profiles of rats in repeated dose toxicological studies after oral and inhalative exposure.

The MetaMap(®)-Tox database contains plasma-metabolome and toxicity data of rats obtained from oral administration of 550 reference compounds following a standardized adapted OECD 407 protocol. Here, metabolic profiles for aniline (A), chloroform (CL), ethylbenzene (EB), 2-methoxyethanol (ME), N,N-dimethylformamide (DMF) and tetrahydrofurane (THF), dosed inhalatively for six hours/day, five days a week for 4 weeks were compared to oral dosing performed daily for 4 weeks. To investigate if the oral and inhalative metabolome would be comparable statistical analyses were performed. Best correlations for metabolome changes via both routes of exposure were observed for toxicants that induced profound metabolome changes. e.g. CL and ME. Liver and testes were correctly identified as target organs. In contrast, route of exposure dependent differences in metabolic profiles were noted for low profile strength e.g. female rats dosed inhalatively with A or THF. Taken together, the current investigations demonstrate that plasma metabolome changes are generally comparable for systemic effects after oral and inhalation exposure. Differences may result from kinetics and first pass effects. For compounds inducing only weak changes, the differences between both routes of exposure are visible in the metabolome.

[Aging and age-related changes of the vitreous body]. / Gesunder Glaskörper und seine Alterung.

BACKGROUND AND PURPOSE: The vitreous body is the largest component of the eye. It is a colorless, gelatinous, highly hydrated matrix that fills the posterior segment of the eye between the lens, the ciliary body and the retina. Changes in vitreal structure that occur with aging, such as vitreous liquefaction and fiber aggregation (vitreous syneresis) are important in the pathogenesis of many vitreoretinal diseases. During senescence, the vitreous volume is reduced, the vitreous body collapses and the vitreal fibers are continuously thickened, become more tortuous and surrounded by liquefied vitreous. This sequence of age-related changes results from a progressive reorganization of the hyaluronic acid and collagen molecular networks. RESULTS AND DISCUSSION: Although the vitreous body may at first glance appear to be a redundant tissue than can be removed and almost normal ocular function will still be maintained, the vitreous body and the vitreoretinal interface have a crucial influence on the physiology and pathophysiology of the eye. Age-related liquefaction and vitrous syneresis play an essential pathogenetic role in the development of posterior vitreous detachment, retinal breaks and retinal detachment.

Refractive errors, visual impairment, and the use of low-vision devices in albinism in Malawi.

BACKGROUND: This study focuses on the refractive implications of albinism in Malawi, which is mostly associated with the burden of visual impairment. The main goal was to describe the refractive errors and to analyze whether patients with albinism in Malawi, Sub-Saharan Africa, benefit from refraction. METHODS: Age, sex, refractive data, uncorrected and best-corrected visual acuity (UCVA, BCVA), colour vision, contrast sensitivity, and the prescription of sunglasses and low vision devices were collected for a group of 120 albino individuals with oculocutaneous albinism (OCA). Refractive errors were evaluated objectively and subjectively by retinoscopy, and followed by cycloplegic refraction to reconfirm the results. Best-corrected visual acuity (BCVA) was also assessed binocularly. RESULTS: One hundred and twenty albino subjects were examined, ranging in age from 4 to 25 years (median 12 years), 71 (59 %) boys and 49 (41 %) girls. All exhibited horizontal pendular nystagmus. Mean visual acuity improved from 0.98 (0.33) logMAR to 0.77 (0.15) logMAR after refraction (p < 0.001). The best improvement of VA was achieved in patients with mild to moderate myopia. Patients with albinism who were hyperopic more than +1.5 D hardly improved from refraction. With the rule (WTR) astigmatism was more present (37.5 %) than against the rule (ATR) astigmatism (3.8 %). Patients with astigmatism less than 1.5 D improved in 15/32 of cases (47 %) by 2 lines or more. Patients with astigmatism equal to or more than 1.5 D in any axis improved in 26/54 of cases (48 %) by 2 lines or more. CONCLUSIONS: Refraction improves visual acuity of children with oculocutaneous albinism in a Sub-Saharan African population in Malawi. The mean improvement was 2 logMAR units.

[Retinoblastoma in Malawi: why are admissions too late?]. / Retinoblastom in Malawi : Warum zu späte Einweisung?

BACKGROUND: A total of 82 % of stationary admissions with the diagnosis of retinoblastoma (2009-2011) to the tertiary ophthalmology unit in Blantyre, Malawi (n = 58) presented with advanced stage disease. PATIENTS AND METHODS: In another study in 2012 we sought to identify why children mostly presented in advanced stages of disease and whether the delay was unique to children with cancer. In-depth interviews (IDI) were conducted at the hospital with 40 parents or guardians of children with retinoblastoma, congenital cataract, congenital glaucoma and corneal perforation (10 each). RESULTS: Most delays and delayed admissions occurred at the family (27.5 %, 11 out of 40) and primary health centre levels (30.0 %, 12 out of 40). Lack of money for transport caused delays (15.0 %, 6 out of 40) at all care levels. In contrast, children with painful conditions presented to a health facility within 24 h of onset without any complaints about lack of money for transport. CONCLUSION: Education about retinoblastoma and other non-painful eye diseases could be improved by a poster campaign to both parents and professionals at all medical healthcare levels. Transport for such cases between the various healthcare centers should be provided free of charge. There is room for improvement in initial diagnosis, referral and management within the healthcare service in the tertiary sector.