[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.

[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.

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.

[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.

[The role of the ophthalmologist in the management of juvenile neuronal ceroid lipofuscinosis]. / Relevanz ophthalmologischer Diagnostik für die Betreuung von Patienten mit juveniler neuronaler Ceroid-Lipofuszinose.

BACKGROUND: Neuronal ceroid lipofuscinoses (NCL) are storage diseases leading to severe somatic and mental deterioration with blindness and death. To date, there are no therapeutic options. Juvenile NCL (JNCL), also known as Batten's disease, is one of the most prevalent forms of NCL. MATERIALS AND METHODS: A 6-year-old boy with the primary diagnosis of retinitis pigmentosa was examined. The parents reported a rapid deterioration of vision during the past months. In view of this history, additional, non-ophthalmological diagnostic procedures have been performed (peripheral blood smear, molecular genetics). RESULTS: The eye examination showed a considerable reduction of visual acuity, a concentric visual field constriction, an extinguished electroretinogram and a bull's eye maculopathy. The peripheral blood smear revealed vacuolated lymphocytes. Molecular genetic investigation confirmed the diagnosis of juvenile NCL by detecting a homozygous (1-kb deletion of the CLN3-gene). CONCLUSIONS: The ophthalmologist plays a key role for an early diagnosis of juvenile NCL. An early diagnosis is important for the affected families because only then they can handle this stroke of fate.

Clinical and electrophysiologic results after intracameral lidocaine 1% anesthesia: a prospective randomized study.

OBJECTIVE: To evaluate the efficacy and safety of intracameral lidocaine in cataract surgery compared to peribulbar anesthesia. DESIGN: A prospective, randomized, controlled study. PARTICIPANTS: A total of 200 consecutive cataract patients (200 eyes) participated. INTERVENTION: Eyes were randomly assigned to two groups: one group received 0.15 ml intracameral 1% unpreserved lidocaine combined with topical anesthesia (oxybuprocaine); the other group received 6 ml prilocaine peribulbar before phacoemulsification with sclerocorneal tunnel incision. MAIN OUTCOME MEASURES: Duration of surgery was measured; implicit time and amplitudes of the b-waves of the photopic electroretinogram (ERG) potentials (single-flash ERG and the 30-Hz flicker ERG) were recorded; frequencies of intraoperative problems, complications, intraoperative, and postoperative pain were evaluated. RESULTS: After lidocaine anesthesia combined with topical anesthesia, similar complications were found, longer operation time (P < 0.001), and significantly better visual acuity immediately after surgery (P < 0.001). The ERG amplitudes were not significantly reduced after 0.15-ml intracameral lidocaine half an hour after surgery (P > 0.05). CONCLUSION: Intracameral lidocaine 1% combined with topical anesthesia can be recommended as an alternative procedure to peribulbar anesthesia in cataract surgery with corneoscleral tunnel incision.

Recurrent NF1 gene mutation in a patient with oligosymptomatic neurofibromatosis type 1 (NF1).

We report a 21-year-old male with symptomatic optic glioma who does not fulfill the diagnosis of neurofibromatosis 1 (NF1) according to standard NIH criteria. Analysis of the NF1 gene revealed a recurrent mutation in exon 37 (C6792A or Y2264X). This nonsense mutation causes skipping of exon 37 during the splicing process and is predicted to result in a protein shortened by 34 amino acid residues. The mutation was detected in all tissues examined (blood lymphocytes, oral mucosa, and dermal fibroblasts). The same mutation was previously found in 3 patients with clinically confirmed NF1. To our knowledge, this is the first report of an adult patient carrying a putative (non-mosaic) NF1 gene mutation in multiple tissues but not fulfilling the NIH criteria for the clinical diagnosis of NF1.

Prognostic value of the pattern electroretinogram in cases of tumors affecting the optic pathway.

BACKGROUND: Tumors compressing the optic pathway may lead to irreversible loss of vision which may be detected by the pattern electroretinogram (PERG) because of its relation to ganglion cell function. METHODS: Eyes of 19 patients were tested shortly before and 5-10 days after tumor surgery. Visual acuity, the 30-deg visual field and the transient and steady-state pattern reversal ERG were measured. RESULTS: Using patterns of 1.5 x 1.2 deg there was a good correlation between the change of pre- and post-surgical visual performance and most of the pattern ERG amplitudes. For all variables tested--P50, N95- and steady-state amplitude--there was a critical value beyond which the visual outcome could be bad or favorable, whereas patients showing higher amplitudes always remained stable or improved after surgery. CONCLUSION: The positive correlation between pattern ERG amplitudes and the post-surgical outcome in the case of tumors affecting the optic pathway may be helpful in predicting the outcome for these patients.

[Juvenile neuronal ceroid lipofuscinosis (Batten-Mayou) disease. Ophthalmologic diagnosis and findings]. / Juvenile neuronale Zeroidlipofuszinose (Batten-Mayou). Augenärztliche Diagnostik und Befunde.

BACKGROUND: Juvenile neuronal ceroid lipofuscinosis (JNCL) is important to the ophthalmologist, since eye symptoms are usually the first evidence of the disease and permit establishment of an early diagnosis. The disorder usually begins with a dramatic loss of vision between age 4 and 10 due to bulls-eye maculopathy followed by rapid degeneration of the retina and pigment epithelium. Blindness results within 1 to 3 years after onset of symptoms. The further course of the disease is mainly determined by degradation of the CNS with motor and intellectual deficits. Most patients die before the age of 30. METHODS: A case of two sisters is presented to demonstrate eye findings and diagnostic procedures, emphasizing electrophysiologic and morphologic tests (peripheral blood smear, histology). RESULTS: Both sisters reported the first decrease in vision at the ages of 8 and 6 respectively; visual acuity at time of visit was light projection (20/400). Both had tapetoretinal degeneration with optic disc atrophy, narrowed vessels, pigment epitheliopathy and bullseye maculopathy. The ERG was almost extinguished in the older sister and greatly reduced in the younger one (scotopic more than photopic). Histologically, vacuolated lymphocytes were found in the peripheral blood smear, as were intracellular inclusions of the fingerprint and curvilinear type in the conjunctival biopsy. CONCLUSION: During the course of JNCL, it is very common for the vision to be affected at the age of 6-7. The correct diagnosis, however, is often made years later when massive neurologic symptoms such as seizures appear. When there is sudden loss of vision in a child of this age combined with a tapetoretinal degeneration, a biopsy or at least a peripheral blood smear should be performed.

[Developments in ophthalmologic electrophysiology]. / Entwicklungen in der ophthalmologischen Elektrophysiologie.

During the last years electrophysiology in ophthalmology has been facilitated to a big extent by computerized methods. Thus it has become a suitable method for an increasing number of relevant diagnostic problems. To make comparisons between test results of different diagnostic places easier an international standard concerning the methodology of the electroretinogram (ERG) has been elaborated by the "International Society of Clinical Electrophysiology in Vision" (ISCEV). Aim of the present article is to give a short description of the ERG-standard and to review recent developments in clinical electrophysiology in ophthalmology (ca. since 1989).