Antje Neugebauer

Counterrotation of the globe in macular translocation

Abstract Background: Macular translocation is a new treatment option in age-related maculopathy. The aim of this study was to report experience with the handling of the sensory problems concerning subjective cyclorotation and binocularity that arise with this technique. Methods: The data of 33 patients who had undergone macular translocation and counterrotation of the globe by muscle surgery in a first operation, followed by silicone oil removal and sometimes revision of the eye muscles in a second operation, were evaluated. The counterrotation consisted of a partial transposition of the rectus muscles and extensive surgery on the anterior margins of the oblique eye muscles. Subjective monocular cyclorota- tion, motility and binocularity were tested. Results: In 5 patients after the two operations binocular single vision was proved; in one of these cases there was even stereoscopic function. Seventeen patients excluded one eye: 13 excluded the operated eye, 4 the fellow eye. Eleven patients experienced double vision or tilted images under binocular viewing conditions and thus required further surgery or occlusion of one eye. Conclusion: The majority of patients were not hindered by subjective cyclorotation. Nevertheless, in a large proportion of patients binocularity could not be reestablished because of still reduced visual acuity or cyclotropia. The data show that the aim of restoring binocularity can be achieved but in practice is often not attained.

Mutation of POC1B in a Severe Syndromic Retinal Ciliopathy

We describe a consanguineous Iraqi family with Leber congenital amaurosis (LCA), Joubert syndrome (JBTS), and polycystic kidney disease (PKD). Targeted next‐generation sequencing for excluding mutations in known LCA and JBTS genes, homozygosity mapping, and whole‐exome sequencing identified a homozygous missense variant, c.317G>C (p.Arg106Pro), in POC1B, a gene essential for ciliogenesis, basal body, and centrosome integrity. In silico modeling suggested a requirement of p.Arg106 for the formation of the third WD40 repeat and a protein interaction interface. In human and mouse retina, POC1B localized to the basal body and centriole adjacent to the connecting cilium of photoreceptors and in synapses of the outer plexiform layer. Knockdown of Poc1b in zebrafish caused cystic kidneys and retinal degeneration with shortened and reduced photoreceptor connecting cilia, compatible with the human syndromic ciliopathy. A recent study describes homozygosity for p.Arg106ProPOC1B in a family with nonsyndromic cone‐rod dystrophy. The phenotype associated with homozygous p.Arg106ProPOC1B may thus be highly variable, analogous to homozygous p.Leu710Ser in WDR19 causing either isolated retinitis pigmentosa or Jeune syndrome. Our study indicates that POC1B is required for retinal integrity, and we propose POC1B mutations as a probable cause for JBTS with severe PKD.

Modified transposition procedure of the vertical recti in sixth nerve palsy

PURPOSE To report a modified transposition procedure of the vertical recti for severely limited abduction of the globe caused by sixth nerve palsy and to compare this with the Hummelsheim transposition procedure. METHODS Retrospective study of 13 eyes of 12 patients that had Hummelsheim transposition procedure and 19 eyes of 17 patients that had modified transposition procedure of the vertical recti for severely limited abduction of the globe caused by sixth nerve palsy. The modified transposition procedure joins lateral strips of the vertical recti and sutures this junction to the lateral rectus muscle. Functional results of the Hummelsheim procedure are compared with functional results of the modified transposition procedure. RESULTS Abductive capacity improved by 4.19 +/- 1.67 mm in the Hummelsheim group and 4.08 +/- 1.7 mm in the modification. The angle of squint changed from +22.33 +/- 6.74 degrees to -0.20 +/- 2.61 degrees in the Hummelsheim group and from +25.54 +/- 5.66 degrees to +0.95 +/- 5.26 degrees in the modification group. The functional results as to abductive capacity and postoperative angle of squint showed no significant difference between the two methods (P >.05, t test). The modification was less time consuming. CONCLUSIONS A modification of the transposition techniques of eye muscles in sixth nerve palsy is introduced. Its functional results are comparable to the classic technique of Hummelsheim. Operative risk and trauma are reduced, because the technique avoids scleral stitches and was found to be less time consuming than the Hummelsheim procedure.

Ocular neuromyotonia: a case report.

Ocular neuromyotonia is a rare motility disorder occurring after tumor irradiation near the skull base or as a consequence of vascular abnormalities. Ocular myasthenia, convergence spasm and a cyclic third nerve palsy must be considered as differential diagnoses. The case of a 32-year-old woman suffering from intermittent diplopia six months after radiation therapy of a recurrent pituary gland adenoma is presented.

A cost-effectiveness model of screening strategies for amblyopia and risk factors and its application in a german setting.

Purpose. To develop a general setting–independent decision-analytical model that determines the costs, effectiveness, and cost-effectiveness of four screening strategies to detect amblyopia or amblyogenic factors in pre-school children and to apply the model in a German setting. Methods. The general setting–independent decision–analytical model was developed from the perspective of society and the statutory health insurance was developed. Outcomes were the total number of newly detected true positive cases of amblyopia and the costs per newly detected true positive case of amblyopia. Strategies were screening of high-risk children up to the age of 1 year (ophthalmologists), screening of all children up to the age of 1 year (ophthalmologists), screening of all children aged 3 to 4 years (pediatricians or general practitioners), and screening of children aged 3 to 4 years visiting kindergarten (orthoptists). For the application example in a German setting, data from the published medical literature were used. Results. In the base-case analysis of the application example, screening high-risk children by opthalmologists had the lowest average cost per case detected but became dominated (less effective and more costly than an alternative) if a low (5.3%) probability of familial clustering of strabismus was assumed. Considering the various assumptions tested in the sensitivity analysis, screening of all children up to the age of 1 year by opthalmologists was the only strategy not dominated by others. Detection rates, including cases detected before screening, were between 72% and 78% for the strategies that screen for all children. Conclusions. The model suggests that in Germany, both from a cost-effectiveness and a pure effectiveness point of view, screening all children up to the age of 1 year by opthalmologists is the preferred strategy to detect amblyopia or amblyogenic factors. All strategies left a significant portion of children undetected.

Ophthalmological manifestations of Parry-Romberg syndrome

Parry-Romberg syndrome is a rare disease characterized by slowly progressive atrophy affecting facial subcutaneous tissues, including the underlying muscles and osteocartilaginous structures. Various periocular, ocular, and neuro-ophthalmological manifestations have been described in Parry-Romberg syndrome. The most common periocular disorders include enophthalmos, eyelid, and orbit alterations. The most frequent ocular disorders include corneal and retinal changes, and the most common neuro-ophthalmological disorders involve optic nerve, ocular motor and pupillary dysfunction. Besides the characteristic facial abnormalities, systemic manifestations may occur, including neurologic, dermatologic, cardiac, endocrine, infectious, orthodontic, and maxillofacial disorders. So far, mainly brief case reports describe these ophthalmological findings. Therefore, we summarize the ocular, periocular, and neuro-ophthalmological findings in detail, describe diagnostic modalities, and outline therapeutic options.

A Novel Large In-Frame Deletion within the CACNA1F Gene Associates with a Cone-Rod Dystrophy 3-Like Phenotype

Cone-rod dystrophies (CORDs) represent a heterogeneous group of monogenic diseases leading to early impairment of vision. The majority of CORD entities show autosomal modes of inheritance and X-linked traits are comparably rare. So far, three X-chromosomal entities were reported (CORDX1, -X2 and -X3). In this study, we analysed a large family of German origin with solely affected males over three generations showing a CORDX-like phenotype. Due to the heterogeneity of cone-rod dystrophies, we performed a combined linkage and X-exome sequencing approach and identified a novel large intragenic in-frame deletion encompassing exons 18 to 26 within the CACNA1F gene. CACNA1F is described causative for CORDX3 in a single family originating from Finland and alterations in this gene have not yet been reported in other CORDX pedigrees. Our data independently confirm CACNA1F as the causative gene for CORDX3-like phenotypes and detailed clinical characterization of the family expands the knowledge about the phenotypic spectrum of deleterious CACNA1F alterations.

Congenital Cranial Dysinnervation Disorders: Facts and Perspectives to Understand Ocular Motility Disorders

Congenital cranial dysinnervation disorders (CCDDs) are a group of neurodevelopmental diseases of the brainstem and the cranial nerves. Endogenic or exogenic disturbances lead to a primary dysinnervation of structures supplied by cranial nerves. Motility disturbances and potentially structural changes occur. Secondary dysinnervation occurs if fibers of other cranial nerves innervate the primarily misinner-vated structures. Synkinetic movements or cocontractions of antagonists result and may lead to structural changes in the muscles involved. Neurogenetic studies proved congenital fibrosis of the extraocular muscles (CFEOM), isolated and syndromic forms of Duane syndrome and horizontal gaze palsy with progressive scoliosis (HGPPS) to be related to mutations in genes that play a role in brainstem and cranial nerve development. By clinical features and theoretic considerations some forms of congenital ptosis, congenital fourth nerve palsy, Mobius syndrome and Marcus Gunn jaw winking phenomenon are understood as CCDDs. Other congenital disturbances of ocular motility with fibrotic features such as congenital Brown syndrome, congenital monocular elevation palsy and vertical retraction syndrome may be discussed as CCDDs.

Makulatranslokation mit 360°-Retinotomie zur Behandlung der exsudativen Makuladegeneration: Funktionelle und angiographische Ergebnisse

ZusammenfassungHintergrund. Mit dem Ziel einer Stabilisierung oder Verbesserung der visuellen Funktion von Patienten mit altersabhängiger Makuladegeneration (AMD) wurde die Translokation der Makula auf gesundes Pigmentepithel (RPE) nach Extraktion einer chorioidalen Neovaskularisation (CNV) entwickelt. Methodik. In einer prospektiven Fallserie nach kontrolliertem Operations- und Untersuchungsprotokoll wurden funktionelle und angiographische Veränderungen nach Makulatranslokation bei 100 Patienten im Verlauf eines Jahres untersucht. Das operative Vorgehen umfasst eine Phakoemulsifikation und Implantation einer Hinterkammerlinse, vollständige Vitrektomie, induzierte Netzhautablösung, 360° anteriore Retinotomie, Entfernung des subretinalen Membrankomplexes, Translokation der Fovea aus dem RPE-Defekt, Wiederanlage der Netzhaut unter Verwendung von Perfluorcarbonen, Endolaserkoagulation und temporäre Silikonöltamponade. Überwiegend erfolgte eine Zyklorotation des Bulbus in Kombination mit dem Primäreingriff oder der Silikonölablassung. Patienten. Im Zeitraum Dezember 1997 bis Dezember 1999 wurden 100 Patienten am Zentrum für Augenheilkunde der Universität zu Köln nach dieser Technik operiert. Alle Patienten hatten eine Visusreduktion infolge einer chorioidalen Neovaskularisation bei AMD erlitten. Bei 26 Patienten lag eine nach rtPA- und Gasinjektion persistierende submakuläre Blutung vor, bei 39 Patienten bestand eine okkulte CNV, bei 25 Patienten eine klassische CNV, bei 10 Patienten lagen andere Formen (polypoidale Vaskulopathie, Pigmentepitheleinriss, chorioretinale Anastomosen) vor. Ergebnisse. Es konnten 97 Patienten über 12 Monate postoperativ kontrolliert werden. Die Sehschärfe stieg 12 Monate postoperativ bei 24 Patienten um mindestens 15 ETDRS-Zeichen an, blieb bei 42 Patienten stabil und fiel um mindestens 15 ETDRS-Zeichen bei 34 Patienten ab. Die Silikonöltamponade war bei 97 Patienten entfernt worden. Ein Revisionseingriff wegen schwerer Komplikationen wurde bei 25 Patienten notwendig (primäre PVR n=9, sekundäre PVR n=10, Makulapucker n=5, Makulaforamen n=1). Als weitere Komplikationen traten eine persistierende okuläre Hypotonie, Keratopathie, IOL-Dislokation, Makulaödem, CNV-Rezidiv (n=3) und Zyklodeviation auf. Schlussfolgerung. Das Operationsverfahren stellt einen aufwändigen und technisch anspruchsvollen Eingriff mit langer Lernphase sowie einem hohen intraoperativen und postoperativen Komplikationsprofil dar. Nach unseren Ergebnissen erscheint die Makulatranslokation dennoch eine aussichtsreiche Therapieform für ausgewählte Patienten mit exsudativer AMD zu sein.AbstractBackground. During surgical extraction of choroidal neovascular membranes (CNV) in age-related macular degeneration (AMD), the defective foveal retinal pigment epithelium (RPE) is removed. Subsequent translocation of the foveal neural retina to adjacent healthy RPE should result in stabilization and possibly improvement of visual acuity. Methods. A prospective case series was carried out using controlled surgery and examination protocols with examinations made at fixed intervals. The surgical procedures combine counterrotation of the globe, phacoemulsification and implantation of a posterior chamber lens, complete vitrectomy, induction of a total retinal detachment, 360° anterior retinotomy, removal of the subfoveal neovascular complex, foveal translocation outside the RPE defect, reattachment of the retina using F6H8, peripheral laser retinopexy and temporary silicone oil tamponade. Patients. Macular translocation surgery was performed on 100 patients between December 1997 and December 1999. All patients had experienced recent visual loss due to exudative AMD and of these, 26 patients had major macular subretinal hemorrhage, 39 patients had occult and 25 patients classic subfoveal choroidal neovascularization. The preoperative findings in the remaining patients included tears in the pigment epithelium (n=4), polypoidal choroidal vasculopathy (n=1), recurrent subfoveal CNV following laser therapy (n=2) and deep retinal vascular anomalous complexes (n=3). Results. A total of 97 patients completed the 12-month examination. Visual acuity increased by 15 or more ETDRS chart letters in 24 patients, remained stable in 42 patients and deteriorated by 15 or more EDTRS chart letters in 34 patients 12 months postoperatively. The silicone oil tamponade was removed in 97 patients, in 10 patients, silicone oil had to be reinjected because of severe complications. A secondary procedure was necessary in 25 patients, primary PVR was observed in 9 eyes, secondary PVR deve-loped in 10 eyes, a macular pucker in 5 eyes and a macular hole in 1 patient. Other postoperative complications included persistent hypotonia, macular edema, IOL dislocation, keratopathy and recurrent CNV (n=3). Conclusions. Macular translocation is a technically demanding operation, which requires a considerable learning curve. Although the procedure has a high rate of surgical and postoperative complications, the functional and anatomical results appear to be promising for selected patients with subfoveal CNV secondary to AMD.

The cost-effectiveness of screening strategies for amblyopia: a preliminary report.

Five screening strategies for amblyopia in different age groups were compared according to a decision-analytical model from the perspective of the health insurance funds. Our findings indicate that the costs per detected case of amblyopia range from about 1200 DM to 3000 DM (613 Euro to 1534 Euro). The two most cost-effective screening strategies were to screen high-risk children up to the age of one by ophthalmologists and to screen all children up to the age of one by ophthalmologists. The screening of high-risk children identifies only about a third of all affected children in this age group, when compared with the number of cases detected by screening all children up to the age of one. However, the average cost per detected case of amblyopia among high-risk children is lower than the cost of screening all children in this age range.