[Microstructural retinal changes after pharmacological vitreolysis with ocriplasmin-an SD-OCT supported analysis]. / Mikrostrukturelle retinale Veränderungen nach pharmakologischer Vitreolyse mit Ocriplasmin ­ eine SD-OCT-gestützte Analyse.

PURPOSE: Ocriplasmin (Jetrea®) is a therapeutic option for patients with focal vitreomacular traction (VMT) with or without small full thickness macular holes (FTMH) < 400 µm. Retinal alterations after injection with ocriplasmin have been described. The purpose of this essay was to determine Ocriplasmin-associated side-effects and changes in the retinal microstructure. METHODS: We included 70 patients with ocriplasmin treatment in our study. On all patients SD-OCT (spectral-domain optical coherence tomography) scans were performed prior to injection with Ocriplasmin. If present, adverse events were registered. The OCT scans were then evaluated taking the following into account: macular hole (MH) size, macular edema, subretinal fluid (SRF), changes in the ellipsoid zone (EZ) and the external limiting membrane (ELM). RESULTS: Twenty of the 70 examined patients showed a preoperative FTMH. One week after ocriplasmin IVI (intravitreal injection) 8 of the 20 FTMHs were already closed. Overall 12 patients showed a FTMH closure and 4 patients developed a FTMH after ocriplasmin IVI. Twelve of the 24 MH (macular hole) patients still required an operative closure of the FTMH. We noticed a resolution of the VMT on 51 patients. Three patients developed a retinal detachment. Furthermore, after ocriplasmin IVI we detected changes in the EZ and ELM on 8 patients. CONCLUSIONS: Ocriplasmin is a substantial minimal invasive option in the therapy of VMT with or without small FTMH. Nevertheless, there seem to be some specific ocriplasmin-associated risks, although usually transient. Severe complications like retinal detachment are rare but exist. Therefore, every indication of ocriplasmin should be considered carefully.

[Non-Arteritic Ischemic Optic Neuropathy (NAION)]. / Die nicht arteriitische anteriore ischämische Optikusneuropathie (NAION).

Non-arteritic ischemic optic neuropathy (NAION) is virtually unknown outside ophthalmology. It is characterised by acute unilateral visual loss, no pain on eye movements and virtually always optic disc swelling. Optic disc oedema resolves within 1 to 2 months, leaving behind optic atrophy. Vision hardly improves. NAION is the product of local abnormalities of the vascular supply to the optic nerve and general vascular risk factors. Of these, diabetes, hypertension and especially sleep apnoea syndrome are the most important. Recurrences in the involved eye are rare; contralateral recurrence occurs in approximately 15 % of patients. There is no clear scientific evidence for any specific therapy. However, there is general agreement that it is reasonable to control risk factors.

[Current recommendations on optic neuritis]. / Aktuelle Empfehlungen zur Neuritis nervi optici.

BACKGROUND: The diagnostics and therapy of optic neuritis are complex and require interdisciplinary cooperation. AIM: Compact, up-to-date recommendations for the clinician appear to be desirable. MATERIAL AND METHODS: A selective literature search including the authors' professional experience was carried out. An algorithm for the practical approach to optic neuritis was derived from the best available evidence. RESULTS: Our recommendation distinguishes between compulsory and optional investigations. Differential diagnostic cues with regard to atypical optic neuritis and other optic neuropathies are shown. Standard therapy patterns and means of escalation are suggested. Indications for referral are presented. CONCLUSION: The algorithm suggested in this article provides ophthalmologists with an effective orientation aid for the complete treatment procedure of optic neuritis.

[Pseudotumor cerebri syndrome]. / Pseudotumor cerebri.

Pseudotumor cerebri is a non-tumor related idiopathic or secondary intracranial hypertension. It is typically associated with papilledema and headache and patients are typically female, young and obese. Diagnosis is established by neuroimaging by magnetic resonance imaging (MRI), cerebral MR venography (MRV) and lumbar puncture. Papilledema is assessed by ophthalmoscopy, ultrasound and optical coherence tomography. Ophthalmologists monitor visual function by measuring visual acuity and visual field testing. Therapy of patients not facing immediate visual loss encompasses weight reduction and administration of carbonic anhydrase inhibitors. In vision-threatening situations invasive procedures are necessary, such as repeated lumbar puncture, liquor drainage, optic nerve sheath fenestration and endovascular venous stenting.

[Ophthalmologic screening history and vision-targeted health status of patients suffering from chloroquine maculopathy]. / Screeninganamnese und sehkraftbezogene Lebensqualität von Patienten mit Chloroquin-Makulopathie.

BACKGROUND: Maculopathy or retinopathy can develop as a side effect of chloroquine intake. Despite recommendations for ophthalmologic screening by the American Academy of Ophthalmology (AAO) severe toxic retinal damage still occurs. This study aims to clarify how maculopathy affects patient quality of life and whether it arises only due to non-compliance with screening guidelines. METHODS: Patients suffering from chloroquine maculopathy were questioned about the ophthalmologic examinations that took place under therapy and completed a German version of the 25 item visual function questionnaire (VFQ-25). RESULTS: A total of ten female patients were included in the analysis. Weighted visual acuity ranged from 0.09 to 0.8. Median composite score of the VFQ-25 was 33.9. All patients were periodically screened for ocular toxicity with a median trimestrial screening frequency but five patients did not receive all recommended methods of examination. There was suspicion of retinal damage in only one patient even without the patient reporting complaints. Median time span between onset of visual complaints and the cessation of the drug was 12 months. All patients with complaints reported a continuing deterioration of vision even after cessation. CONCLUSIONS: Chloroquine maculopathy has a major impact on the vision-related health status of affected patients, emphasizing the need for its anticipation. Although patients were screened even more frequently than recommended by the AAO only half were examined properly and nine out of ten patients had a delay in diagnosis and in drug cessation. The continuing deterioration of vision even after termination of intake further contributes to the severity of the disease.

[Two-wall decompression without resection of the medial wall. Effect on squint angle]. / Zwei-Wand-Dekompression ohne Resektion der medialen Wand. Einfluss auf den Schielwinkel.

BACKGROUND: Postoperative new onset diplopia can be a disadvantage for surgical orbital decompression in patients with exophthalmos in thyroid eye disease. The various modifications of decompression (number and combination of walls) differ in their influence on the postoperative squint angle. We report on postoperative diplopia in a modified 2 wall decompression strategy (lateral wall and floor). METHODS: This study was a retrospective analysis of 36 consecutive 2-wall decompressions performed between 2006-2010 in 24 patients with 6 months of stable exophthalmos in thyroid eye disease after medical therapy and radiotherapy. The preoperative and postoperative squint angle in prism cover test (PCT), motility, induction of diplopia, reduction of exophthalmos, visual acuity and complications were evaluated. RESULTS: In all 36 decompressions the postoperative squint angle was equal to or less than before surgery. In 8 eyes additional squint surgery was performed. The mean reduction in exopthalmos was 4.3 mm. CONCLUSIONS: An adverse effect of decompression on the postoperative squint angle was not evident in this study. New induction of diplopia was not observed at all. One possible explanation is the preservation of the medial wall.

Evaluation of risk factors for retinal damage due to chloroquine and hydroxychloroquine.

BACKGROUND/AIMS: To evaluate risk factors for retinal damage due to the intake of chloroquine and hydroxychloroquine. METHODS: In a retrospective chart review, patients receiving or having received one of the drugs were classified as affected by maculopathy or retinopathy, or as not affected on the basis of the documented findings. Uncertain cases were excluded. The risk factors as postulated by the American Academy of Ophthalmology (AAO) and additional factors like diagnosis of underlying disease, total dose, nicotine abuse and the sum of the AAO risk factors were compared between both groups. RESULTS: 51 patients with a history of or ongoing treatment with chloroquine (23 individuals) or hydroxychloroquine (28 individuals) were included. Most of the postulated risk factors were expectedly elevated in the affected group. Significant differences applied to age, duration of intake and the sum of AAO risk factors. Surprisingly, positive smoking history was more frequent in the not affected. The toxic threshold of the daily chloroquine dose was exceeded by most of the patients. CONCLUSIONS: Age and the duration of intake are major risk factors. Smoking seems to be negligible. The sum of AAO risk factors can give an estimation of the individual risk profile. Individual and weight-adapted dosing is especially essential for chloroquine.

[NCL in animal models]. / Neuronale Zeroidlipofuszinosen (NCL) im Tiermodell.

Neuronal ceroid lipofuscinoses (NCL) are severe neurodegenerative diseases leading to early death. They belong to the group of lysosomal storage diseases. Epileptic seizures, dementia and motor deficits are frequent symptoms which are to be found prior to a total dismantling of personality and death. At present 10 subtypes of NCL can be distinguished from which the genetic defect is known in eight. The encoded proteins are soluble or membrane proteins whose function is still unclear in most cases. The investigation of the pathology and pathophysiology of NCL is highly dependent on animal models. Mouse models existing for all forms with a known genetic defect play a prominent role. Unfortunately, the retinal phenotype of some mouse models is milder than in humans rendering the appreciation of a positive therapeutic effect more difficult. Because of the severity of NCL, therapy strategies only established in a mouse model will be transferred to humans very quickly.

[Juvenile neuronal ceroid lipofuscinosis. Ophthalmologic findings and differential diagnosis]. / Juvenile neuronale Zeroidlipofuszinose. Ophthalmologische Diagnostik und Differenzialdiagnose.

Neuronal ceroid lipofuscinoses (NCL) are a heterogeneous group of neurodegenerative diseases with mostly autosomal recessive inheritance whose common feature is the intralysosomal accumulation of ceroid lipofuscin. With varying manifestation ages the diseases result in cognitive and motor deterioration, epilepsy, diffuse retinal degeneration, and eventually death. Juvenile ceroid lipofuscinosis (JNCL, CLN3, Batten disease) has the distinctive feature that the ophthalmologic symptoms precede the neurologic symptoms by several years, and thus the ophthalmologist plays a central role in early diagnosis. Important clinical signs of JNCL include bull's eye maculopathy, severely reduced Ganzfeld ERG already at initial presentation, and unusually rapid progression of the functional decline. If JNCL is clinically suspected the diagnosis can be made by means of a standard blood smear and confirmed by genetic detection of the mutation. Although causal therapeutic options are currently only in the developmental stage, early diagnosis by the ophthalmologist is of utmost importance to allow for medical and educational support of the affected child and for adequate counseling of the parents.

[Retinal damage by (hydroxy)chloroquine intake: published evidence for an efficient ophthalmological follow-up]. / Netzhautschädigung bei (Hydroxy-)Chloroquin-Einnahme: Evidenzlage als Basis für eine rationale augenärztliche Untersuchungsstrategie.

BACKGROUND: Irreversible maculopathy and retinopathy are well-known adverse effects of chloroquine and hydroxychloroquine. For this article the literature was screened for relevant risk factors. The results were used for recommendations concerning the extent and frequency of ophthalmological monitoring. METHODS: A systematic literature review was undertaken. RESULTS: Very few studies on a high evidence level could be retrieved for this problem. Most of the risk factors have not been addressed sufficiently. A higher dosage per kg body mass, long therapy duration, presence of keratopathy and renal or hepatic dysfunction are probably associated with an increased risk to develop a maculopathy/retinopathy. Additional factors such as age, genetic disposition, additional retinal disease, sunlight exposition and nature plus duration of the underlying disease have not sufficiently been demonstrated. Gender, body mass and even the accumulated dosage do not contribute as risk factors according to current knowledge. CONCLUSION: Beside patient risk factors, the spectrum of ophthalmological methodology and cost considerations have to be considered when thinking about content and frequency of monitoring for the risk of acquiring a (hydroxy)chloroquine-induced maculopathy or retinopathy. In principle, a baseline examination comprising visual acuity (near and far), 10 degree threshold perimetry, colour vision, slit lamp (cornea) and funduscopy is reasonable. One of the high investment techniques such as multifocal ERG, fundus autofluorescence and high resolution optical coherence tomography should be used depending on the existing equipment and experience but not more often than once a year. In suspicious cases or high risk-patients a flexible approach is mandatory.

[Development of disease-specific patient groups within Pro Retina]. / Entwicklung diagnosespezifischer Gruppen in der Pro Retina.

The formation, development and external impact of the following eight disease-specific patient groups with rare forms of retinal degeneration (RRD) within the patient organization Pro Retina are described: Gyrate Atrophy, Bardet-Biedl Syndrome (BBS), Adult Refsum's Disease, Usher Syndrome, Rod-Cone Dystrophy, Leber's Congenital Amaurosis, Choroideremia and Stargardt Disease/juvenile macular degeneration. Within the project sponsored by the German Ministry of Health (BMG) approaches of patient self-help for an adequate organization and interaction with the professional medical care system were supported, analyzed and documented. In syndromic RRD a relatively high proportion of patients are organized in patient groups (Refsum's disease 25%, BBS 14%, Usher Syndrome 8%). Patients with syndromic RRD are more highly motivated to contribute to self-help work than patients with non-syndromic RRD. At the same time, these patients are more dependent on the support from their relatives and on technical aids. The following tendencies in the development of RRD groups were observed: increasing focus on one patient organization (PRO RETINA Deutschland, Self-Help Organisation of People with Retinal Degenerations) all RRD groups in Pro Retina grew; RRD groups became increasingly independent within Pro Retina; external activities of the groups showed considerable increase. Stable work relationships with scientific and medical care institutions have been established. The example of RRD demonstrates how rare and isolated patients receive basic coping support by self-help groups, how they deal with resources in a collective way and how they can interact with the medical care system.

Protracted course of juvenile ceroid lipofuscinosis associated with a novel CLN3 mutation (p.Y199X).

The juvenile neuronal ceroid lipofuscinosis (JNCL, Batten disease, MIM 204200), is an autosomal recessive lysosomal storage disease, which is characterized by ubiquitous accumulation of the lipopigment material ceroid-lipofuscin. It manifests with loss of vision in childhood due to retinal degeneration, followed by seizures and parkinsonism leading to premature death at around 30 years. Eighty-five percent of JNCL patients carry a disease-causing 1.02 kb deletion in the CLN3 gene on chromosome 16. Here we report on a large consanguineous Lebanese family with five affected siblings. Electron microscopy of lymphocytes revealed the presence of fingerprint profiles suggesting JNCL. However, disease progression, especially of mental and motor function was slower as expected for 'classic' JNCL. We thus confirmed the diagnosis by genetic testing and found a new c.597C>A transversion in exon 8, homozygous in all affected family members and not present in 200 alleles of normal controls. The mutation generates a premature termination codon (p.Y199X) truncating the CLN3 protein by 55%. In heterozygous state mutant mRNA transcripts are expressed at the same levels as the wild-type ones, suggesting the absence of nonsense mediated messenger decay. We discuss a potential residual catalytic function of the truncated protein as a cause for the mild phenotype.

Fourier transformed steady-state flash evoked potentials for continuous monitoring of visual pathway function.

Monitoring of somatosensory, motor and auditory pathway function by evoked potentials is routine in surgery placing these pathways at risk. However, visual pathway function remains yet inaccessible to a reliable monitoring. For this study, a method of continuous recordings was developed and tested. Steady-state visual evoked potentials were elicited by flash stimulation at 16 Hz and analysed using discrete Fourier transform. Amplitude and phase of the fundamental response were dynamically averaged and continuously plotted in a trend graph. The method was applied on awake individuals with normal vision and on patients undergoing neurosurgery. In most individuals it was possible to continuously record significant responses. Surprisingly, characteristic time-courses of amplitude and phase were observed in several subjects. These findings were attributed mainly to flicker-adaptation. During anesthesia, amplitude and signal-to-noise ratio were markedly smaller. Signal recognition was facilitated when potentials were recorded with a subdural electrode placed directly at the occipital pole. The anesthetic agent propofol had a major impact on the recordings.

[Patient participation in medical care, taking rare retinal degenerations as examples]. / Patientenselbsthilfe und seltene Erkrankungen. Mitgestaltung der Versorgungsrealität am Beispiel seltener Netzhautdegenerationen.

Eight rare retinal degenerations were chosen to exemplify self-organisation and involvement of patient self-help groups in medical care. They were studied and supported in their development on the following levels: disease-specific groups (level 1), patient organisations (level 2), umbrella organisation (level 3). Databases of defined needs and concerns ("Themenspeicher") of disease-specific patient groups and of patient organisations with respect to care, research and patient networking were established. Priority concerns were implemented in the following areas: specialised medical care; quality assurance; quality management; expert panel with international dialogue of patients and physicians (including consensus statement on treatment recommendations); glossary internet portal; criteria for patient-oriented disease descriptions; structured documentation of patient experiences; patient management of health care records (paper bound and electronic health records). Apart from disease- specific approaches, interdisciplinary disease approaches were also applied, e.g. by contributing to the establishment of the German Alliance for Rare Diseases (ACHSE). This umbrella organisation has substantially improved chances for cooperation and patient advocacy. Patient participation was promoted by a federal regulation in 2004 ("Patientenbeteiligungsverordnung"). The example of rare retinal degenerations demonstrates the advantage of strong patient and umbrella organisations. Further development of qualified self-help resources is required for patient participation in rare diseases.

[Chloroquine/hydroxychloroquine: variability of retinotoxic cumulative doses]. / Variabilität der retinotoxischen Gesamtdosis Chloroquin/Hydroxychloroquin.

OBJECTIVE: The critical dose of chloroquine/hydroxychloroquine leading to a maculopathy or generalised retinopathy remains undetermined. In the literature, 100 g is considered the dose at which regular vision checks should be performed. Generally, chloroquine is said to be more toxic than hydroxychloroquine. A young patient presenting with toxic maculopathy after 57 g of hydroxychloroquine and a daily dosage of 2 mg/kg body weight prompted us to retrospectively look at our patients examined in this respect over about 1 year. METHODS: The data of patients who were examined because of chloroquine/hydroxychloroquine intake or a respective maculopathy/retinopathy were retrospectively analysed. The time period was January 2005 until March 2006. Retinal damage was defined by fundus changes and alteration of the multifocal electroretinogram (ERG). RESULTS: Twenty-one patients--18 women and three men--were examined. The mean age was 51 years (range 6-71). Five of the nine chloroquine-treated patients developed a maculopathy, and one of them developed an additional generalised retinopathy. Of the patients treated by hydroxychloroquine, three of 12 suffered from a maculopathy and one from an additional generalised retinopathy. The cumulative doses leading to retinal damage ranged from 170 g to 1650 g for chloroquine and from 57 g to 1190 g for hydroxychloroquine. The highest cumulative doses without leading to signs of retinopathy were 790 g for chloroquine and 1200 g for hydroxychloroquine. CONCLUSIONS: There is a high variability of cumulative doses of chloroquine/hydroxychloroquine that lead to a toxic retinopathy. Therefore, early and regular ophthalmologic examinations are recommended. Electrophysiological testing should be performed once a year, corresponding to about 60 g of base with one tablet a day. For electrophysiology, the multifocal ERG has turned out to be the most important test in this regard. However, visual acuity and funduscopy should be performed more frequently.