Hermann Krastel

Static fundus perimetry using the scanning laser ophthalmoscope with an automated threshold strategy

Abstract• Purpose: The purpose of this study was to develop software that allows the performance of routine static threshold perimetry using the scanning laser ophthalmoscope (SLO) and the comparison of the results with conventional computerized cupola perimetry. The original software does not allow performance of static threshold perimetry within a reasonable examination time. • Methods: Static perimetry was performed in random order on 50 healthy eyes using our SLO staircase threshold perimetry technique and the Octopus 500 (program 38). We compared the relative sensitivities for each of 25 corresponding visual field locations. • Results: Mean sensitivity in the SLO perimetry amounted to 32.7 dB (range 25–37 dB) while it was 28.7 dB in the Octopus. For all test locations the SLO showed higher dB values on average. The mean difference between both methods was 3.7±0.8 dB (range 1.4–5.8 dB) when the test locations at the blind spot were excluded (linear regression between the two methods: r=0.843, P<0.0001). The mean time interval between two stimulus presentations was 2.5 s with the SLO perimetry. • Conclusion: With the Heidelberg software, automated static threshold perimetry using the SLO is possible within reasonably short examination times. The mean time interval between two test point presentations is about one tenth of that necessary using the original Rodenstock software. There is a systematic difference between SLO and Octopus fields of about 4 dB which was not very much influenced by the stimulus locations.

Ophthalmological Aspects of Pierson Syndrome

PURPOSE To study the ocular phenotype of Pierson syndrome and to increase awareness among ophthalmologists of the diagnostic features of this condition. DESIGN Retrospective, observational case series. METHODS A multicenter study of 17 patients with molecularly confirmed Pierson syndrome. The eye findings were reviewed and compared to pertinent findings from the literature. RESULTS The most characteristic ocular anomaly was microcoria. A wide range of additional abnormalities were found, including posterior embryotoxon, megalocornea, iris hypoplasia, cataract, abnormal lens shape, posterior lenticonus, persistent fetal vasculature, retinal detachment, variable axial lengths, and glaucoma. There was high interocular and intrafamilial variability. CONCLUSIONS Loss-of-function mutations in laminin beta2 (LAMB2) cause a broad range of ocular pathology, emphasizing the importance of laminin beta2 in eye development. Patients with Pierson syndrome can initially present with ocular signs alone. In newborns with marked bilateral microcoria, Pierson syndrome should be considered and renal function investigated.

Mutations in CNGA3 impair trafficking or function of cone cyclic nucleotide-gated channels, resulting in achromatopsia

CNGA3 encodes the A‐subunit of the cone photoreceptor cyclic nucleotide‐gated (CNG) channel, which is a crucial component of the phototransduction cascade in cone outer segments. Mutations in the CNGA3 gene have been associated with complete and incomplete forms of achromatopsia (ACHR), a congenital, autosomal recessively inherited retinal disorder characterized by lack of color discrimination, reduced visual acuity, nystagmus, and photophobia. Here we report the identification of three novel CNGA3 missense mutations in ACHR patients: c.682G>A (p.E228 K), c.1315C>T (p.R439W), and c.1405G>A (p.A469 T), and the detailed functional analyses of these new as well as five previously reported mutations (R283Q, T291R, F547L, G557R, and E590 K), in conjunction with clinical data of patients carrying these mutations, to establish genotype–phenotype correlations. The functional characterization of mutant CNGA3 channels was performed with calcium imaging and patch clamp recordings in a heterologous HEK293 cell expression system. Results were corroborated by immunostaining and colocalization experiments of the channel protein with the plasma membrane. Several mutations evoked pronounced alterations of the apparent cGMP sensitivity of mutant channels. These functional defects were fully or partially compensated by coexpressing the mutant CNGA3 subunit with the wild‐type CNGB3 subunit for channels with the mutations R439W, A469 T, F547L, and E590 K. We could show that several mutant channels with agonist dose–response relationships similar to the wild‐type exhibited severely impaired membrane targeting. In addition, this study presents the positive effect of reduced cell culture temperature on surface expression and functional performance of mutant CNG channels with protein folding or trafficking defects. Hum Mutat 0,1–9;, 2008.

Immune-mediated retinopathy in a patient with stiff-man syndrome

Abstract · Background: Stiff-man syndrome is a rare neurological disorder characterised by rigidity and violent spasms of the body musculature. In the majority of patients, presence of antibodies against glutamic acid decarboxylase (GAD), the enzyme synthesizing γ-aminobutyric acid (GABA), suggests an autoimmune attack against GABA-ergic inhibitory neurons. We report a 32-year-old patient with stiff-man syndrome and anti-GAD antibodies who developed subacute progressive loss of vision in the right eye, and in the left eye 18 months thereafter. · Methods: Ophthalmological work-up included electro-retinogram (ERG), visual evoked potentials (VEP) and fluorescein angiography. Antiretinal antibodies were investigated using an indirect immunofluorescence technique on frozen sections of macaque retina with patient´s serum and FITC-conjugated goat antihuman immunoglobulin. Staining with monoclonal anti-GAD65 antibodies and with serum from three healthy normals served as controls. · Results: Visual acuity of both eyes decreased to 0.16 within a span of 6 weeks. Perimetry revealed a central scotoma in the visual field of both eyes. VEP and flash ERG were progressively disturbed on the right eye. On the left eye, initially only pattern ERG and photopic responses were abnormal. Follow-up recordings revealed widespread pathology of photopic single and flicker responses. Immunofluorescence revealed strong reactivity of the inner plexiform layer and to a lesser extent staining of the outer plexiform layer at dilutions of 1:1000 with patients serum. The same retinal staining pattern was obtained with monoclonal anti-GAD65 antibodies. · Conclusions: These findings suggest autoimmune retinopathy, mediated by anti-GAD65 autoantibodies as the underlying cause of visual loss.

Cataracta complicata bei verschiedenen Formen der Retinitis pigmentosa Art und Häufigkeit

Purpose: To study the incidence and types of cataract in retinitis pigmentosa (RP) and their variations among different forms of RP.Patients and methods: This analysis was based on data from 473 patients with RP (autosomal dominant, n=87; autosomal recessive, n=79; x chromosomal recessive, n=23; simplex RP, n=215; Ushers syndrome n=80; M. Refsum and others, n=9) that were retrieved from the literature and patient charts in our clinic.Results: Posterior subcapsular cataract (PSC) developed with the following frequencies for the different genetic types of RP: autosomal dominant, 45.3%; autosomal recessive, 44.0%; x chromosomal recessive, 40.7%; simplex RP, 46.1%; Ushers syndrome, 52.9%. PSC was the only type of lens opacity in patients with Ushers syndrome and autosomal recessive RP. PSC development correlated with early onset of RP symptoms. Nuclear cataracts showed a statistically significant higher frequency in patients with simplex RP (14.8%) than in other genetic types (0–5.9%) (P<0.01). In addition, nuclear cataracts developed in simplex RP at a significantly later age (69.6±12.4 years) than PSC (44.4±12.3 years) (P<0.001). Patients with cataracts showed significantly worse visual fields than patients with clear lenses (P=0.00067).Conclusions: The typical RP cataract (PSC) was found in similar frequencies among all genetic types of RP. PSC was the only type of lens opacity in patients with Ushers syndrome and autosomal recessive RP. Nuclear cataracts developed on average 20 years later than PSC and had their highest incidence in patients with simplex RP. Patients with cataracts showed significantly worse visual field results, indicating a more pronounced retinal pathology.Hintergrund: Ziel dieser Studie war es, die Häufigkeit und die Art der Katarakt bei Retinitis pigmentosa (RP) und deren Ausprägung bei den verschiedenen Vererbungsformen der RP zu untersuchen.Patienten und Methode: Zur Auswertung kamen Daten von insgesamt 473 Patienten mit RP (autosomal-dominant n=87, autosomal-rezessiv n=79, X-chromosomal-rezessiv n=28, Simplex-RP n=215, Usher-Syndrom n=60, Morbus Refsum u.a. n=9), die aus der Literatur und aus dem eigenen Patientenkollektiv zusammengestellt wurden.Ergebnisse: Für die für RP typische Trübungsform der Cataracta subcapsularis posterior (PSC) fand sich folgende Häufigkeitsverteilung: autosomal-dominant 45,3%, autosomal-rezessiv 44,0%, X-chromosomal-rezessiv 40,7%, Simplex-RP 46,1%, Usher-Syndrom 52,9%. Bei den Patienten mit Usher-Syndrom und autosomal-rezessiver RP war die PSC die einzige Trübungsform. Kerntrübungen traten bei Patienten mit Simplex-RP signifikant häufiger auf (14,8%) als bei den anderen Vererbungsformen (0–5,9%, p<0,001). Des weiteren zeigte sich, daß Kerntrübungen bei Simplex-Patienten in einem signifikant höheren Lebensalter (69,6±12,4 Jahre) auftraten als eine PSC (44,4±12,3 Jahre; p<0,001). Patienten mit Katarakt zeigten zudem signifikant schlechtere Gesichtsfeldbefunde als Patienten ohne Katarakt (p=0,00067).Schlußfolgerungen: Die RP-typische Cataracta subcapsularis posterior kommt bei den verschiedenen Vererbungsmodi in ähnlicher Häufigkeit vor. Bei den hier geprüften Patienten mit Usher-Syndrom und autosomal-rezessiver RP war die PSC sogar die einzige erfaßte Trübungsform. Kerntrübungen bei RP traten erst in höherem Alter auf und waren am häufigsten mit der Simplex-Form assoziiert. Patienten mit Kataraktausbildung zeigten zusätzlich deutlich schlechtere Gesichtsfeldbefunde, was ein Hinweis für eine stärker ausgeprägte retinale Pathologie in dieser Gruppe ist.

Posterior capsule opacification and problems of Nd:YAG laser capsulotomy in retinitis pigmentosa

Background: Retinitis pigmentosa (RP) is associated with the development of a posterior subcapsular cataract (PSC). The development of posterior capsule opacification (PCO) after cataract surgery and a decrease of central visual acuity is sometimes misinterpreted by the patients as natural course of RP. Therefore, therapeutic intervention is often delayed. Patients and methods: In a retrospective study (part 1) the incidence of PCO was evaluated in a group of 26 RP patients who underwent cataract surgery and IOL implantation. In a prospective analyse (part 2) PCO was quantified in 13 RP patients using the standardized photographic technique and image analysis system introduced by Tetz et al. Matched pairs were formed with a control group of 13 patients without retinal disease who matched the RP group in terms of age distribution and postoperative follow-up time. In part 3 the parameters of Nd:YAG laser capsulotomy in 12 RP patients and 14 controls were evaluated. Results: Part 1: The cumulative PCO rate in RP at the end of the first postoperative year was 14.6 %, 26.8 % in the second, 53.7 % in the third and 70.7 % after the third year. Nd:YAG laser capsulotomy was performed in 70 % of eyes (after 18.4 ± 14.7 months). In eyes with significant PCO development 70 % had PSC preoperatively, while in eyes without PCO formation only 41.7 % showed PSC. Part 2: The matched pairs analysis showed a significantly higher PCO value for RP patients (2.11 ± 1.42) than for the control group (0.89 ± 0.72) (P = 0.038). Part 3: Average Nd:YAG laser energy levels were 12.8 ± 11.2 MJ (RP) and 7.6 ± 6.7 MJ (control). Some 25 % of RP patients required further laser treatment of regrown secondary cataract. Conclusions: Patients with RP showed a significantly higher incidence and density of PCO. Whether RP-specific pathomechanisms are responsible for this needs further investigation.Hintergrund: Patienten mit Retinitis pigmentosa (RP) entwickeln schon in jungen Jahren eine Cataracta complicata. Nach erfolgter Kataraktoperation wird die Ausbildung einer Cataracta secundaria und ein damit einhergehender Visusabfall von den Patienten häufig dem Verlauf der RP zugeordnet und die Möglichkeit einer therapeutischen Intervention nicht bedacht. Patienten und Methoden: Die Nachstarinzidenz wurde im Teil 1 der Studie retrospektiv bei 41 Augen von 26 RP-Patienten, die eine postoperative Nachbeobachtungszeit von mindestens 3 Monaten aufwiesen, untersucht. Im Teil 2 dieser Studie wurde bei 13 RP-Patienten mit dem Nachstar-Bildanalyse-System nach Tetz die Nachstarausprägung quantifiziert und in einem Paarvergleich mit einer Kontrollgruppe von 13 netzhautgesunden Patienten verglichen. Im Teil 3 wurden die Energiemengen zur Nd:YAG-Laser Kapsulotomie von 12 RP-Patienten und 15 netzhautgesunden Patienten verglichen. Ergebnisse: Teil 1: Die kumulative Nachstarrate der RP-Patienten betrug im ersten postoperativen Jahr 14,6 %, im zweiten 26,8 %, im dritten 53,7 % und erreichte bei den Patienten, mit einem Nachbeobachtungszeitraum > 36 Monaten, 70,7 %. Bei 70 % der Augen mit Nachstar mußte eine Nd: YAG-Laser Kapsulotomie durchgeführt wurde (nach 18,4 ± 14,7 Monaten). 70 % der Augen der Nachstargruppe zeigten als Kataraktform die typische subkapsuläre posteriore Katarakt, während diese in der Gruppe ohne Nachstarbildung nur in 41,7 % vorlag. Teil 2: der gematchte Paarvergleich zeigte für die RP-Patienten mit einem Nachstarwert von 2,11 ± 1,42 einen signifikant höheren Wert als die Kontrollgruppe (0,89 ± 0,72) (p = 0,038). Teil 3: Die durchschnittliche Nd:YAG-Laserenergiemenge betrug für die Gruppe der RP-Patienten 12,8 ± 11,2 mJ, für die Vergleichsgruppe 7,6 ± 6,7 mJ. 25 % der RP-Patienten mußten nachgelasert werden. Schlußfolgerungen: Patienten mit Retinitis pigmentosa weisen eine signifikant höhere Nachstarrate und Nachstarausprägung auf, die sich auch klinisch in einen höheren Energiebedarf bei der Nd:YAG-Laserkapsulotomie ausdrückt. Ob RP-spezifische Pathomechanismen hierfür verantwortlich sind, läßt sich z. Z. noch nicht abschließend beurteilen. Hierfür sind weitere Studien notwendig.

Objektivierung der Sehfunktionen bei Begutachtungen

ZusammenfassungZur Prüfung des Sehvermögens ist eine möglichst objektive Bestimmung der Sehfunktion anzustreben. Ophthalmologische Basisuntersuchungen wie Visusprüfung und Perimetrie sind jedoch von den Angaben des Patienten abhängig. Sofern der Untersuchte keine geeigneten subjektiven Angaben machen kann, wie dies für Kleinkinder oder geistig Behinderte zutrifft, aber auch bei Zweifeln an der Richtigkeit der Angaben und gar dem Verdacht auf Simulation oder Aggravation, ist bei der Beurteilung der Sehleistung grundsätzlich die angegebene Funktion mit verschiedenen Untersuchungsmethoden auf ihre Richtigkeit zu überprüfen und der Befund objektiver Prüfverfahren wie der elektrophysiologischen Zusatzdiagnostik zusammen mit dem morphologischen Befund zu berücksichtigen.AbstractFor the determination of visual function an objective assessment is essential. Basic ophthalmologic examinations such as measurement of visual acuity and perimetry are dependent on patient statements. If the patient is not being able to provide adequate answers, as is the case for small children or mentally retarded patients, or also if the accuracy of the patient’s statements is doubtful or simulation or aggravation is suspected, the denoted function in the evaluation of visual acuity has to be checked on consistency using different examination methods, and the results of objective functional tests, such as electrophysiology and morphological features, have to be taken into account.

Karzinomassoziierte Retinopathie (CAR) bei Mammakarzinom und Karzinoid

Fragestellung: Die Karzinomassoziierte Retinopathie (CAR) stellt ein seltenes paraneoplastisches Syndrom dar, das bislang am häufigsten bei kleinzelligen Bronchialkarzinomen beschrieben wurde. Wir berichten über 3 Patientinnen mit CAR in Gegenwart eines Mammakarzinoms bzw. eines Karzinoids der Cervix uteri.Patienten und Methode: Es wurden biomikroskopische, perimetrische, angiographische und elektrophysiologische Befunde erhoben. Außerdem erfolgte eine Testung der Immunreaktivität der Seren an humaner Retina.Ergebnisse: Die Befunde umfaßten ringförmige Gesichtsfelddefekte mit statokinetischer Dissoziation und eine pathologische Stäbchen- und Zapfenantwort im ERG. Bei 1 Patientin wurde immunhistochemisch eine Reaktion im Bereich der Photorezeptorinnensegmente, der äußeren Körnerschicht sowie der äußeren plexiformen Schicht bei fehlendem Nachweis von Antikörpern gegen Recoverin gefunden.Diskussion: Neben dem kleinzelligen Bronchialkarzinom können auch andere Primärtumoren mit einer CAR vergesellschaftet sein. Der Nachweis von retinalen Autoantikörpern unterstützt die Annahme einer tumorinduzierten Immunantwort aufgrund der Expression identischer Epitope durch die Tumorzellen. Dabei kommen offensichtlich verschiedene retinale Proteine als Autoantigene in Betracht.Background: Carcinoma-associated retinopathy (CAR) is a rare paraneoplastic syndrome characterized by diffuse retinal photoreceptor degeneration in the presence of an epithelial tumor. We report on three patients, who developed paraneoplastic retinopathy in the presence of breast carcinoma and a cervical carcinoid tumor.Materials and methods: In addition to biomicroscopic, psychophysical, electrophysiological and angiographic examinations, serum samples were obtained for immunohistochemical staining of human retina.Results: Ring-shaped visual field defects with statokinetic dissociation and abnormal rod and cone responses were found. Immunohistochemical findings included reactions at the level of the inner segments of the photoreceptors, the outer nuclear layer and the outer plexiform layer in absence of antirecoverin antibodies.Conclusions: CAR should be considered in the differential diagnosis of visual loss in presence of tumors other than small-cell carcinoma of the lung. The presence of antiretinal antibodies is compatible with a tumor-induced immune response to epitopes shared by both the tumor and retinal tissue. Apparently, various retinal proteins may function as autoantigens.

Congenital Glaucoma in Cutis marmorata teleangiectatica congenita

A case of congenital glaucoma in cutis marmorata teleangiectatica congenita (CMTC, van Lohuizen syndrome) is described. The cutaneous anomaly and heterochromia iridium were noticed at birth. Brown discoloration of one iris was due to iris anterior layer dysplasia, resulting in unilateral glaucoma. Two trabeculotomies were performed until persistent normalization of intraocular pressure could be achieved. The possibility of a genetic basis and hereditary condition of CMTC and its association with congenital glaucoma is discussed. Patients with CMTC should regularly undergo ophthalmological follow-up to rule out development of glaucoma.

Comparison of VEP with contrast sensitivity and other measurements of central visual function.

Purpose:  In order to evaluate alternative visual acuity testing techniques, especially to discriminate between small changes and for high visual acuity, we conducted a study covering several state‐of‐the‐art techniques.