[Therapeutic management of a kissing nevus of the eyelid]. / Therapeutisches Management eines "kissing nevus" des Augenlids.

Congenital divided melanocytic nevi of the upper and lower eyelid are rare pigmented changes of the eyelids. These processes are also known as "kissing nevi," "panda nevi," and "split ocular nevi," and were first described by Fuchs in 1919. About 120 cases have been described in the literature so far. Congenital melanocytic nevi are either present at birth (small nevi are already found in about 1% of neonates) or manifest predominantly during the first decade of life. These rare melanocytic changes of the eyelids should be controlled regularly, as malignant transformation can occur. The actual incidence of malignant transformation is highly variable in the literature, ranging from 2 to 40% depending on the duration of follow-up, with an average of 14% for the whole lifetime. Moreover, nevi of the eyelids may be considered cosmetically disturbing and cause functional problems. Therapeutic removal (dermabrasion, cryotherapy, laser therapy, and surgical excision with ophthalmoplastic reconstruction) is rarely medically indicated due to the low risk of malignant transformation. Removal can be performed in cases of secondary amblyopia in ptosis, compression of the lacrimal point, epiphora, or cosmetic desire. Treatment becomes necessary not only in case of suspicious manifestation or impairment of eyelid function, but it also helps to avoid possible bullying at school among children and is recommended at age 4 to 6 (before school age).

Surgical excision of eyelid tumors and subsequent ophthalmoplastic reconstruction.

In recent years new modern therapeutic concepts have been developed in the treatment of malignant eyelid tumors; however, surgical restoration remains an important component of the therapeutic options addressed, which include microsurgical tumor excision into healthy tissue and subsequent coverage of the defects. An ophthalmic surgeon experienced in oculoplastic surgery is responsible for the recognition and evaluation of the existing alterations and planning a procedure together with the patient that meets the patient's expectations. The planning of surgery must always be individualized and fit the initial findings. Depending on the defect size and localization, different coverage strategies are available to the surgeon. To ensure successful reconstruction, every surgeon should master a wide range of reconstructive techniques.

[Surgical excision of eyelid tumors and subsequent ophthalmoplastic reconstruction]. / Chirurgische Exzision von Lidtumoren und anschließende ophthalmoplastische Rekonstruktionen.

In recent years new modern therapeutic concepts have been developed in the treatment of malignant eyelid tumors; however, surgical restoration remains an important component of the therapeutic options addressed, which include microsurgical tumor excision into healthy tissue and subsequent coverage of the defects. An ophthalmic surgeon experienced in oculoplastic surgery is responsible for the recognition and evaluation of the existing alterations and planning a procedure together with the patient that meets the patient's expectations. The planning of surgery must always be individualized and fit the initial findings. Depending on the defect size and localization, different coverage strategies are available to the surgeon. To ensure successful reconstruction, every surgeon should master a wide range of reconstructive techniques.

[The role of citicoline in glaucoma]. / Bedeutung von Citicolin bei der Glaukomerkrankung.

BACKGROUND: In recent years, many experimental and clinical studies have shown that in glaucoma, neuronal degeneration occurs not only at the level of the retina and optic nerve, but also along the entire visual pathway and the brain. OBJECTIVE: This article presents the neuroprotective effects of citicoline and their mechanisms in glaucoma disease. MATERIALS AND METHODS: The relevance of citicoline is explained against the background of neuroanatomy, neuroimaging, and the pathogenesis of glaucoma. Data from experimental and clinical studies are presented and a conclusion is drawn for clinical application. RESULTS: Citicoline has a neuroprotective effect via mechanisms relevant to glaucoma. The neuroprotective effect of citicoline in open-angle glaucoma can be demonstrated functionally and morphologically. It is independent of the glaucoma damage and intraocular pressure, and usually occurs only after 1 year. The effects of oral citicoline occur at a daily dose of 500-1000 mg. Citicoline can be taken permanently or in cycles. No side effects occurred in the studies when taking citicoline. Citicoline can improve cognitive performance and thus treatment adherence as well as quality of life in glaucoma patients. CONCLUSION: This relatively old nootropic drug, which is now marketed as a food supplement, seems to be a valuable addition to conventional treatment and also a rational option for prophylaxis of open-angle glaucoma.

[Trabecular micro-invasive glaucoma surgery : Procedures and clinical results]. / Trabekuläre mikroinvasive Glaukomchirurgie : Verfahren und klinische Ergebnisse.

The management of glaucoma therapy to reduce intraocular pressure commonly consists of a gradual approach with local monotherapy, combined therapy, laser surgery and finally filtration surgery. The local side effects of glaucoma medications and the lack of adherence and persistence to the medical therapy as well as the complication profile of the established glaucoma surgical techniques justify the introduction of new surgical procedures. Micro-invasive glaucoma surgery (MIGS) is a promising new surgical approach. Microstents can reduce the medication burden and prolong the need for filtration surgery. This review article presents the different trabecular implants (iStent, iStent inject, HydrusTM Microstent) in detail and discusses the effectiveness and safety of the procedures based on the currently available data.

[Revision after filtration surgery]. / Revision nach Filtrationschirurgie.

BACKGROUND: In contrast to all other glaucoma surgeries, filtration surgery is associated with biomicroscopically visible wound healing, which enables the surgeon to perform revision surgeries if necessary. OBJECTIVES: The aim of this review is to provide general considerations and to give a structured overview about bleb revisions after trabeculectomy. MATERIALS AND METHODS: The different revision techniques are explained in detail and in the context of perioperative management. RESULTS: Preoperative preparation and modifications of the surgical techniques reduce the incidence of postoperative revisions. The site of the fibrosis defines the revision technique (bleb needling, needle revision, bleb revision with reopening). The increased percolation rate of aqueous humor in postoperative hypotony contributes to fibrosis and may lead to maculopathy, choroidal effusion, and suprachoroidal hemorrhage. DISCUSSION: Discontinuing administration of local medication and pretreatment with steroids without preservative for at least one week prior to surgery increase surgical success of trabeculectomy and reduce the incidence of postoperative revisions. Postoperative management after filtration surgery should be performed after consulting the surgeon. The primary endpoint of trabeculectomy is an intraocular pressure between 8 and 12 mm Hg without local antiglaucomatous medication. In postoperative hypotony revisions should be done earlier and based on the pathological findings.

[Dyslipidaemia and glaucoma]. / Fettstoffwechselstörungen und Glaukom.

Endothelial dysfunction and vascular dysregulation play a role in the multifactorial pathogenesis of glaucomatous optic nerve atrophy. Dyslipidaemia as a risk factor for endothelial dysfunction is associated with glaucoma and cardiovascular morbidity and mortality. In additional to a genetic disposition, a potential mechanism for the pathogenesis of endothelial dysfunction could be an additive effect of several risk factors, like dyslipidaemia, smoking, arterial hypertension, diabetes and hyperhomocysteinaemia. This paper reviews the literature concerning the association between dyslipidaemia and glaucomatous disease and explains the possible role of dyslipidaemia for the pathogenesis and progression of glaucoma. The role of exogeneous modifiable risk factors for prevention and therapy of glaucoma and their neutralisation by changing life style like weight reduction, modifications of nutrition and physical activity, are discussed.

Elevated percentage of HLA-DR⁺ and ICAM-1⁺ conjunctival epithelial cells in active Graves' orbitopathy.

BACKGROUND: To evaluate if conjunctival epithelial cells' expression of HLA-DR and ICAM-1 could be helpful as early topical markers of inflammation in Graves' orbitopathy (GO). METHODS: The ocular examination evaluated a clinical activity score (CAS) by assessment of clinical features, (e.g., eyelid or conjunctival inflammation, lid width, lid closure, proptosis, ocular motility). Conjunctival epithelial cell specimens for flow-cytometric evaluations of ICAM-I and HLADR expression were collected by impression cytology from ten eyes with active GO (CAS ≥ 4 and duration ≤ 12 months), from 15 eyes with Graves' disease (GD) without active GO (CAS 0-2) and from 15 normal specimens without any ocular disorders. RESULTS: The percentage of HLA-DR + conjunctival epithelial cells was significantly elevated in patients with active GO comparing to GD without active GO and healthy controls, 10.7 % (8.5-17.7) and 7.78 % (3.92-10.1) (p < 0.05) vs. control 4.89 % (3.5-5.5) (p < 0.005), respectively. The expression of ICAM - 1+ conjunctival epithelial cells was greater only in patients with GO vs. controls, 5.5 % (4.8-7.03) and 1.46 % (0.69-2.51) (p < 0.005), respectively. CONCLUSION: The percentage of HLA-DR⁺ and ICAM-1⁺ conjunctival epithelial cells in patients with the active GO may serve as a topical inflammation marker in Graves' orbitopathy.

Cerebrospinal fluid biomarkers of ß-amyloid metabolism and neuronal damage in epileptic seizures.

BACKGROUND AND PURPOSE: The main objectives of this study were to investigate if epileptic seizures have effects on brain metabolism of ß-amyloid (Aß), as reflected by cerebrospinal fluid (CSF) levels of different isoforms of Aß peptides and soluble amyloid precursor protein (APP), and neuronal degeneration, as reflected by CSF biomarker signs of acute neuronal injury. METHODS: Forty-five patients were included, 21 of whom had single generalized tonic-clonic seizures sGTCS), 11 had repetitive GTCS, 7 had repetitive partial seizures (rPS), 6 had single partial seizure (sPS) and 4 fulfilled the criterion for non-convulsive status epilepticus (nSE). CSF was analyzed for Aßx-38, Aßx-40, Aßx-42, Aß1-42, soluble APP fragments (sAPP-α/ß), total-tau (T-tau) and phosphorylated tau (P-tau), as well as heart-type fatty acid binding protein (H-FABP). RESULTS: Patients with seizures had decreased levels of T-tau (P = 0.0016) and P-tau (P = 0.0028) compared with controls, but no differences in H-FABP (P = 0.67). There were no overall differences in Aß or sAPP peptides between seizure patients and controls. In patients with rPS, the levels of Aßx-38 and Aßx-40 were elevated compared with nSE (P < 0.01), sPS (P < 0.05) and controls (P < 0.05), and Aßx-42 was elevated in rPS relative to nSE (P < 0.05). CONCLUSIONS: The findings of this study argue against acute neuronal injury following medically treated seizures but suggest that seizures may reduce CSF levels of tau. Although seizures generally did not affect CSF levels of Aß or sAPP peptides, our findings suggest that different types of seizures may have different effects on APP metabolism.

[Medicinal glaucoma therapy. What can we learn from large randomized clinical trials?]. / Medikamentöse Glaukomtherapie. Welche Lehren können wir aus den großen klinischen Studien ziehen?

The prospective multicenter randomized controlled clinical trials (RCTs) Ocular Hypertension Glaucoma Treatment Study (OHTS), Early Manifest Glaucoma Trial (EMGT), Advanced Glaucoma Intervention Study (AGIS), Collaborative Initial Glaucoma Treatment Study (CITGS) and Collaborative Normal Tension Glaucoma Study (CNGTS) are often named as landmarks for glaucoma management as the results of these studies provided the evidence for numerous therapeutic decisions in clinical practice. The studies confirmed the consensus that reduction of intraocular pressure reduces the risk of glaucoma progression covering the whole spectrum of glaucoma from ocular hypertension to advanced glaucoma. Furthermore, the identification of new risk factors allows a higher precision of assessment of the risk of progression. The RCTs achieved the main goal of high level of evidence, thus making progress in the understanding of glaucoma and its treatment and bridging consensus-based and evidence-based decisions. However, the implementation of the results into clinical practice needs adequate and accurate interpretation of the results.

Correlation from undiluted vitreous cytokines of untreated central retinal vein occlusion with spectral domain optical coherence tomography.

PURPOSE: To correlate inflammatory and proangiogenic key cytokines from undiluted vitreous of treatment-naïve central retinal vein occlusion (CRVO) patients with SD-OCT parameters. METHODS: Thirty-five patients (age 71.1 years, 24 phakic, 30 nonischemic) underwent intravitreal combination therapy, including a single-site 23-gauge core vitrectomy. Twenty-eight samples from patients with idiopathic, non-uveitis floaterectomy served as controls. Interleukin 6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and vascular endothelial growth factor (VEGF-A) levels were correlated with the visual acuity (logMar), category of CRVO (ischemic or nonischemic) and morphologic parameters, such as central macular thickness-CMT, thickness of neurosensory retina-TNeuro, extent of serous retinal detachment-SRT and disintegrity of the IS/OS and others. RESULTS: The mean IL-6 was 64.7pg/ml (SD ± 115.8), MCP-1 1015.7 ( ± 970.1), and VEGF-A 278.4 ( ± 512.8), which was significantly higher than the control IL-6 6.2 ± 3.4pg/ml (P=0.06), MCP-1 253.2 ± 73.5 (P<0.0000001) and VEGF-A 7.0 ± 4.9 (P<0.0006). All cytokines correlated highly with one another (correlation coefficient r=0.82 for IL-6 and MCP-1; r=0.68 for Il-6 and VEGF-A; r=0.64 for MCP-1 and VEGF-A). IL-6 correlated significantly with CMT, TRT, SRT, dIS/OS, and dELM. MCP-1 correlated significantly with SRT, dIS/OS, and dELM. VEGF-A correlated not with changes in SD-OCT, while it had a trend to be higher in the ischemic versus the nonischemic CRVO group (P=0.09). CONCLUSIONS: The inflammatory cytokines were more often correlated with morphologic changes assessed by SD-OCT, whereas VEGF-A did not correlate with CRVO-associated changes in SD-OCT. VEGF inhibition alone may not be sufficient in decreasing the inflammatory response in CRVO therapy.

[Influence of mode of delivery on pre-existing eye diseases]. / Einfluss des Geburtsmodus auf vorbestehende Augenerkrankungen.

Many ophthalmologists and obstetricians recommend either an assisted vaginal delivery with forceps or vacuum extraction, or a Caesarean section in cases of pre-existing eye diseases, such as myopia, retinal detachment, glaucoma or diabetic retinopathy. This is mainly based on the increase of intraocular pressure during the final stage of labor. These recommendations, however, are not evidence-based. None of the published trials have reported any retinal changes after vaginal delivery. This report provides information on the influence of physiological changes on eye diseases during the final stage of delivery. In general eye disease is not an indication for an instrumental or operative delivery provided regular eye examinations (once each trimester) have been performed.

Vitamin deficiency and hyperhomocysteinemia in pseudoexfoliation glaucoma.

Pseudoexfoliation syndrome (PEX) is a systemic disorder characterized by the deposition of an abnormal fibrillar material in ocular and various extraocular tissues. It represents the most common identifiable cause of glaucoma (PEX glaucoma = PEXG). Due to similar pathogenetic mechanisms, glaucoma has been called "ocular Alzheimer's disease". PEXG and Alzheimer's disease share common associations such as the higher prevalence of hyperhomocysteinemia in both disorders. In order to investigate the cause of hyperhomocysteinemia in PEXG, we evaluated B-vitamin levels (folate, B12, B6) and their associations with homocysteine (Hcy) in plasma of 70 PEXG patients and 70 control subjects. Folate, vitamin B12 and B6 levels were significantly decreased and associated with elevated Hcy levels in PEXG. Low B-vitamin levels in PEX might also help explain, at least in part, the higher prevalence of B-vitamin deficiency in disorders associated with PEX such as Alzhemier's disease.

Homocysteine levels in aqueous humor and plasma of patients with primary open-angle glaucoma.

We determined homocysteine (Hcy) levels in aqueous humor (AH) and plasma and their association with B-vitamin levels in patients with primary open-angle glaucoma (POAG) and controls. Both AH Hcy and plasma Hcy levels were significantly increased in POAG, and elevation of AH Hcy and plasma Hcy was a significant risk factor for POAG. In contrast to controls, neither plasma nor AH Hcy of POAG patients demonstrated a significant association with important non-genetic determinants of elevated Hcy such as low B-vitamin levels, increasing age and caffeine consumption. Considering that Hcy is a neurotoxin that induces apoptotic retinal ganglion cell death via stimulation of the N-methyl-D-asparate (NMDA) receptor, increased Hcy concentrations in AH and plasma might contribute to the optic nerve damage in POAG.

Kynurenic acid synthesis in bovine retinal slices--effect of glutamate agonists.

The purpose of the present study was to investigate the effect of glutamate agonists upon kynurenic acid (KYNA) production in bovine retinal slices. Quantitative analysis of newly synthesized KYNA was carried out using an HPLC system and detected fluorimetrically. Glutamate at the concentration of 0.01, 0.1 and 1 mM reduced KYNA synthesis in the retinal slices to 70% (p < 0.05), 35% (p < 0.01) and 23% (p < 0.001), respectively. The concentration of glutamate reducing production of KYNA by 50% (IC(50)) was 0.035 mM (0.02-0.06). Aspartate at the concentration of 0.01, 0.1 and 1 mM lowered KYNA synthesis in the retinal slices to 80% (p < 0.01), 57% (p < 0.001) and 43% (p < 0.001), respectively. In contrast, kainic acid (up to 5 mM), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) (up to 1 mM) and 1-aminocyclopentane-trans-1,3-dicarboxylic acid (t-ACPD) (up to 3 mM) turned out to be ineffective in diminishing KYNA synthesis. These data demonstrate that glutamate, aspartate and N-methyl-D-aspartate (NMDA) inhibit KYNA synthesis in bovine retinal slices with different potency.

Presence of kynurenic acid and kynurenine aminotransferases in the inner retina.

Kynurenine aminotransferases (KATs I and II) are pivotal to the synthesis of kynurenic acid (KYNA), the only known endogenous glutamate receptor antagonist and neuroprotectant. This study is the first to identify KYNA in the rat retina and to examine immunohistochemically the distribution of KAT isoforms. As determined by HPLC, KYNA concentration in the retina was 99.9 +/- 24.6 pmol/g wet wt. Immunohisto- chemical experiments showed that both KATs were present in the retina. KAT I was preferentially localised on Müller cell endfeet while KAT II was expressed in cells within the ganglion cell layer. In conclusion, KYNA is present and synthesised in the inner retina. This may suggest a modulatory role in glutamate-mediated retinal neurotransmission.

The effects of citicoline and/or MK-801 on survival, neurological and behavioral outcome of mice exposed to transient hyperglycemia and oligemic hypoxia.

UNLABELLED: The effects of citicoline and/or low dose of MK-801 (sufficient to prevent the development of seizures) on survival, neurological and behavioral recovery following transient hyperglycemic-oligemic-hypoxic insult have been evaluated in mice. Neurological recovery was assessed semi-quantitatively on the third and the 10th day after the insult, and behavioral tests evaluating spontaneous locomotor activity, motor coordination and spontaneous alternation performance were performed on day 10. Neither drug given alone did influence survival rate, but the combination of MK-801 and higher citicoline dose decreased mortality on day 10. Behavioral performance was markedly compromised by the insult. Citicoline, but not MK-801, slightly but significantly improved behavioral outcome in all three tests. CONCLUSION: when brain ischemic insult is complicated with acute hyperglycemia, post-treatment with citicoline combined with MK-801 in low anti-convulsive dose improves survival and neurological recovery, and citicoline but not MK-801 enhances behavioral recovery.

2-deoxyglucose enhances epileptic tolerance evoked by transient incomplete brain ischemia in mice.

The aim of the study was to assess the influence of chronic treatment with a non-metabolisable glucose analogue, 2-deoxyglucose (2-DG) at a 150 mg/kg dose on long-term epileptic tolerance (ET) evoked by 30 min bilateral carotid artery clamping (BCCA) in mice. The effects of protein synthesis inhibition with cycloheximide (CHX), given in three daily doses of 2.5 mg/kg starting either 1 day before (peri-insult regimen) or 1 day after the priming insult (post-insult regimen), on ET development was also studied. Seizures were induced 14 days after BCCA with 3.5 mg/kg of bicuculline; this dose (CD97) evokes convulsions in 97% of normal untreated mice. BCCA resulted in decreased mortality, prolonged latency to the onset of generalised convulsions and decreased overall seizure score. CHX given in the post-insult regimen did not influence, while the peri-insult regimen abolished, all signs of BCCA-evoked ET. 2-DG treatment of sham-operated animals resulted in a moderate but significant decrease in mortality rate and a tendency toward a lower seizure score. BCCA combined with 2-DG treatment resulted in a marked decrease in mortality rate, as well as reduction in all indicators of seizure susceptibility. CHX abolished the antiepileptic effects of BCCA alone, as well as BCCA combined with 2-DG, while it did not influence the 2-DG-related decrease in mortality. We conclude that the development of BCCA-induced epileptic tolerance, as well as unmasking antiepileptic effects of 2-DG by BCCA, is dependent on protein synthesis.

Evidence for intraocular synthesis of kynurenic acid, a putative endogenous neuroprotectant.

Kynurenic acid (KYNA), an excitatory amino acid antagonist preferentially active at glycine binding site of the NMDA receptor, has been previously identified in the brain. This study was designed to examine its presence in the rabbit vitreous humor. Mean (+/- SD) level of KYNA in the vitreous was 22.3 +/- 3.9 pmol/ml as determined by HPLC. Intravitreal administration of 10 mmol aminooxyacetic acid (AOAA), a KYNA synthesis inhibitor, diminished its production by 9.6% after 2 h, 47.8% after 24 h and 21.5% after 48 h. It can be concluded that AOAA decreases the intravitreal concentration of KYNA, providing evidence of its intraocular origin.