Klaus W. Ruprecht

Influence of photodynamic therapy in choroidal neovascularization on focal retinal function assessed with the multifocal electroretinogram and perimetry.

PURPOSE To study the influence of photodynamic therapy (PDT) on retinal function in patients with a predominantly classic choroidal neovascular membrane. DESIGN Comparative observational study. PARTICIPANTS Sixteen eyes with a choroidal neovascular membrane eligible for PDT were included. METHODS Visual acuity, multifocal electroretinogram (MF-ERG, Electrodiagnostic Imaging, San Mateo, CA) recordings and visual fields (Octopus d32) were obtained before PDT with Visudyne, Novartis AG, Basel, Switzerland, and at follow-up 2 weeks to 3 months later. MAIN OUTCOME MEASURES Visual acuity as well as peak-to-peak amplitudes, peak latencies, and focal differences in the scalar product of the two MF-ERG recordings were analyzed. Mean deviation, loss variance, and the absolute difference in sensitivity in the fields obtained were also analyzed. RESULTS After PDT, mean visual acuity stabilized or improved in 13 eyes. Except for two eyes with a predominantly parafoveolar choroidal neovascular membrane, the MF-ERG contribution from the central 4 degrees was reduced below the normal level. Although it improved slightly after PDT, it remained below the normal range. In the central 7.5 degrees, retinal sensitivity increased by up to 80 dB and within the paracentral 7.5 degrees to 15 degrees, it increased by up to 183 dB in 13 eyes. CONCLUSIONS Consistent with the results of the treatment of age-related macular degeneration with photodynamic therapy (TAP) study, PDT can lead to stabilization of visual acuity. Improvement in parafoveal function can be demonstrated in the central visual field, as well as in MF-ERG recordings, even in patients whose visual acuity remains stable. Therefore, the MF-ERG and central perimetry may aid the assessment of retinal function in treatment trials of patients with age-related macular degeneration.

Melanoma-associated retinopathy: high frequency of subclinical findings in patients with melanoma.

Summary Background Melanoma‐associated retinopathy (MAR) is a paraneoplastic syndrome with symptoms of night blindness, light sensations, visual loss, defect in visual fields, and reduced b‐waves in the electroretinogram. Patients with MAR often suffer from a sudden onset of ocular symptoms that are believed to result from antibody production against melanoma‐associated antigens that cross‐react with corresponding epitopes on retinal depolarizing bipolar cells.

Ocular manifestations in a father and son with EEC syndrome

Abstract• Background: The ectrodactyly —ectodermal dysplasia —clefting (EEC) syndrome is a rare disease which follows an autosomal-dominant pattern of inheritance. Due to the ectodermal dysplasia there is atresia of the lacrimal duct system and aplasia of the meibomian glands with a defective tear film. Therefore, vascularized corneal scars often form during early adult life. • Patients: Father aged 41 years, and son aged 23 months.Both patients: stenosis/atresia of lacrimal duct systems (the father had twice undergone dacryocystorhinostomy externally) with epiphora, lip-palate clefting, syndactylies of fingers and toes, lobster deformities of hands.Additional ophthalmological findings in the father: bilaterally extracted juvenile cataracts with implantation of intraocular lenses, bilateral extensive vascularized corneal scars.Additional dermatological findings in the father: malignant melanoma of the calf, now in complete remission following several operations on the melanoma and several cycles of chemotherapy for the metastases. • Discussion and therapeutic conclusions: Father and son show the full clinical picture of the EEC syndrome with clefting, lobster-like deformities of the hands and ectodermal dysplasia with tear duct atresia and aplasia of the meibomian glands with defective tear film. During childhood, the main handicapping features are the clefting and the hand deformities with their respective multiple operative revisions. During early adulthood, however, the ocular problems become the predominantly handicapping aspects of the EEC syndrome; due to the ectodermal dysplasia, vascularized corneal scarring develops. Tearing and secondary inflammation due to lacrimal duct atresia has to be treated by early dacryocystorhinostomy. As secondary infections promote the development of corneal scars, one should not postpone the operation too long. Infections have to be treated promptly by local antibiotics. Because of the aplasia of the meibomian glands, artificial tear substitution should be given on a regular basis to support the defective tear film. Thus, the development of vascularized corneal scars can perhaps be delayed. Once corneal scarring has developed, perforating keratoplasty has a poor prognosis due to the ectodermal dysplasia, the absence of the meibomian glands and the defective tear film. Three factors lead to the formation of vascularized corneal scars: recurrent infections of lid margins and conjunctiva due to obstructed tear ducts; defective tear film with insufficient lipid phase due to the aplasia of the meibomian glands; and primary corneal epithelial defects in the course of the generalized ectodermal dysplasia.

SMCHD1 mutations associated with a rare muscular dystrophy can also cause isolated arhinia and Bosma arhinia microphthalmia syndrome

Arhinia, or absence of the nose, is a rare malformation of unknown etiology that is often accompanied by ocular and reproductive defects. Sequencing of 40 people with arhinia revealed that 84% of probands harbor a missense mutation localized to a constrained region of SMCHD1 encompassing the ATPase domain. SMCHD1 mutations cause facioscapulohumeral muscular dystrophy type 2 (FSHD2) via a trans-acting loss-of-function epigenetic mechanism. We discovered shared mutations and comparable DNA hypomethylation patterning between these distinct disorders. CRISPR/Cas9-mediated alteration of smchd1 in zebrafish yielded arhinia-relevant phenotypes. Transcriptome and protein analyses in arhinia probands and controls showed no differences in SMCHD1 mRNA or protein abundance but revealed regulatory changes in genes and pathways associated with craniofacial patterning. Mutations in SMCHD1 thus contribute to distinct phenotypic spectra, from craniofacial malformation and reproductive disorders to muscular dystrophy, which we speculate to be consistent with oligogenic mechanisms resulting in pleiotropic outcomes.

Vision screening survey of all children starting primary school in 1998 in the Federal State of Saarland, Germany

BACKGROUND. The excellent co-operation with the pediatric public health service of the local health authorities enables us to present the collected results of a vision screening survey of all children starting primary school in 1998 in the Federal State of Saarland. The aim is to analyze the prevalence of amblyopia, strabismus, reduced visual acuity, refractive errors and severe visual impairment in one complete grade of pre-schoolers. METHODS. The examination parameters had been determined in co-operation with the Department of Pediatric Ophthalmology at the University of Saarland and had been fitted to the needs and abilities of lay persons (health workers) doing a vision screening as part of a general health check-up. Parameters were: visual acuity (Rodenstock R21), color vision (Ishihara), stereopsis (Lang), and test for latent hyperopia. Referral to an ophthalmologist if: visual acuity < 0.7; difference in visual acuity in both eyes of more than one line, or any other pathological test result. A total of 12,192 children were screened. RESULTS. The preventive pediatric examinations were complete in 5756 children (56.4%), incomplete in 4449 children (43.6%) and in 1987 children (16.3%) the degree of completion could not be determined. Eyes: pathological findings in 41.7%. Reduced visual acuity in 30.8%, color vision defects in 1.3%, severe visual impairment in 0.3%. Pathological findings in other organ systems: skeleton 33.5%, teeth 32.6%. For the urban confederacy of Saarbr?cken: referrals to ophthalmologists: n=1108. No feedback information: 380; refractive correction: 226; recommendation for regular checks: 346; no pathological findings: 156. CONCLUSION. The high percentage of pathological findings in the vision screening of 12,192 pre-schoolers is an important confirmation that there is a need for a preventive ophthalmologic examination before the age of six. Only an area-wide ophthalmologic vision screening around the second or third year of life can effectively reduce the high prevalence of pathological findings at the time of starting primary school. To improve the present screening situation, networks between ophthalmologists and pediatricians would be beneficial.

Influence of cataract on the multifocal ERG recording: a pre- and postoperative comparison

To study the influence of cataract on the multifocal electroretinogram (mfERG), 18 patients underwent mfERG recordings prior to and following cataract surgery. The central 50° of the retina were stimulated by 103 hexagons alternating independently between white and black according to a binary m-sequence. The frame rate was 75 Hz. The maximum luminance was 200 cd/m2, the minimum luminance <1 cd/m2with a mean luminance of 100 cd/m2. For each retinal location, the latencies of the first negative peak (N1), the first positive peak (P1) and the second negative peak (N2) as well as the amplitude from N1 to P1 and the amplitude from P1 to N2 of the first order response were obtained. Concentric ring averages around the foveal response were analyzed. Following cataract surgery, the mean amplitude of the response in the central four degrees increased from 37.83 to 42.37 for N1P1 (p= 0.019) and from 39.44 to 47.20 for P1N2 (p= 0.001). To reduce the influence of retest variability, each response average was divided by the recordings overall amplitude. For the central 4 degrees this ratio increased by 0.18 (p= 0.002) for N1P1 and by 0.27 (p< 0.001) for P1N2. Clouding of the optic media such as produced by cataracts has a slight but significant influence on the multifocal ERG.

Die Osteo-Odonto-Keratoprothese Ein Resümee nach sechs Jahren operativer Erfahrung

ZusammenfassungEinleitung. Bei Patienten mit stark vaskularisierten Hornhautnarben geht eine Hornhauttransplantation mit einem hohen Abstoßungsrisiko einher. Zur Rehabilitation dieser Patienten kann eine Keratoprothese durchgeführt werden. Methoden. Bei insgesamt 8 Patienten mit okulärem Pemphigoid, nach schwerer Laugenverätzung oder nach Transplantatabstoßung wurde eine Osteo-Odonto-Keratoprothese (OOKP) implantiert. Bei allen Patienten betrug der präoperative Visus am besseren Auge Fingerzählen oder schlechter. Die OOKP wurde jeweils aus einer Zahnwurzel eines Front- oder Eckzahns der Patienten und einem 8 mm langen und zwischen 3 und 4 mm dicken PMMA-Zylinder präpariert und unter eine Mundschleimhautdeckung auf die Hornhaut implantiert. Ergebnisse. Die Nachbeobachtungszeit beträgt im Mittel 3 Jahre Die Implantate sind fest eingeheilt. Das maximale Sehvermögen lag bei 4 Patienten mit intakter Netzhaut zwischen 0,6 und 0,9, bei den übrigen Patienten war es vom Befund der Augenhinterabschnitte abhängig. Das Gesichtsfeld ist bei allen Patienten zentriert. 5 der 8 Patienten hatten postoperativ eine Glaskörperblutung, die sich spontan resorbierte, bei 4 musste eine Korrektur der Schleimhautdeckung der Prothese durchgeführt werden, bei einem führte eine chronische Entzündungsreaktion der Schleimhautdeckung zu einer partiellen Resorption des Zahn-Knochen-Präparats. Ein Patient entwickelte ein sekundäres Winkelblockglaukom, das durch die Implantation einer Ahmed-Valve beherrscht werden konnte. Bei 2 Patienten musste eine retrolentikuläre Membran entfernt werden. Bei keinem der Patienten kam es jedoch zu einem Verlust der Prothese. Schlussfolgerung. Die Ergebnisse zeigen, dass bei einem sonst aussichtslosen kornealen Ausgangsbefund eine Osteo-Odonto-Keratoprothese indiziert sein kann und mittelfristig eine gute optische Rehabilitation ermöglicht.AbstractPurpose. In patients with severe corneal scarring and vascularisation, corneal grafts have a high risk of failure. In those patients an osteo-odonto-keratoprosthesis (OOKP) can be performed. Method. We performed OOKP in eight patients in all with ocular pemphigoid, severe alkali burns, or repulsion of a corneal graft. Each of the patients had finger-counting visual acuity or less. The OOKP consisted of a PMMA cylinder 8 mm long, with a diameter of 3–4 mm, and from a root of the patients tooth. This was implanted in the cornea and covered with buccal mucosa. Results. The medium follow-up was 3 years. The implants are now well incorporated. The best visual acuity was between 0.6 and 0.9 in four patients with intact retinas. In the remaining patients, visual acuity was dependent on the posterior segment findings. The visual field was centred. Five of the eight patients had vitreous bleeding after the operation that was spontaneously absorbed. Revision of the mucous coverage was necessary in four patients, and one of them had a severe inflammation with partial absorption of the bone and tooth implant. One patient developed a secondary angle-closure glaucoma and was treated successfully by implantation of an Ahmed valve. Two patients developed membranes behind the cylinder that were successfully removed. There was no loss of any prosthesis during follow-up. Conclusions. In impasse in severe corneal scars, the osteo-odonto-keratoprosthesis is still indicated and shows good results in visual rehabilitation of patients.

Follow up in open angle glaucoma. A comparison of static perimetry and the fast stimulation mfERG

Purpose:To compare changes in the mfERG to visual field changes observed in OAG. Methods: Twenty-nine eyes with OAG were included. Visual fields (Octopus d32) and mfERGs (VERIS™) were obtained at a mean interval of 9 months (SD 6 months). MfERG recording parameters were as follows: 103 hexagons stimulated the central 50 degrees. M-sequence 25, stimulus base interval 13.33 ms, Lmax 200 cd/m2, contrast 99%. First (KI) and second (KII) order response components were analyzed for the individual quadrants of the visual field and compared to the corresponding mean deviation (MD) of the static perimetry. Results: Changes in visual field parameters and changes in the mfERG did not differ significantly. Overall, as mean deviation increased there was a tendency for implicit times to increase and for amplitudes to decrease. However, over the follow up interval of 9 months only minor changes were observed. The second order response component correlated best with changes in MD (p < 0.05). These were the correlation between MD and KII N1 (r : 0.36) in the upper temporal field, between MD and KII N2 (r : 0.40) in the upper nasal field and between MD and KII P1 (r : 0.38) in the lower temporal field. When a subgroup of 10 eyes that had been tested at least 3 times over 16.8 months (SD 5.5) was examined there were still only minor changes observed in either parameter. Conclusion: While the changes over time in the mfERG and the visual field showed a reasonable correlation, changes observed in either parameter were extremely small over the time period observed, thus requiring a longer follow up and/or a more sensitive stimulation technique.

Antiphospholipid Antibodies in Ocular Arterial and Venous Occlusive Disease

Purpose: It was the aim of this study to evaluate antiphospholipid antibodies (APA), i.e. lupus anticoagulants (LA) and anticardiolipin (ACA) IgG and IgM, in ophthalmic occlusive disease. Methods: Over a 3.5-year period, APA were evaluated in 368 patients. Results: Eighty-six patients (23.4%), compared to 5% in the general population, tested positive for APA. APA did not differ significantly between patients with venous (20.6%) or arterial (25.5%) occlusive disease. This included 93 patients with central retinal vein occlusion (18% APA positive), 67 with retinal branch vein occlusion (24% APA positive), 41 with central retinal artery occlusion (22% APA positive), 53 with retinal branch artery occlusion (32% APA positive), 71 with anterior ischemic optic neuropathy (23% APA positive), 12 with posterior ischemic optic neuropathy (33% APA positive) and 31 patients with amaurosis fugax (23% APA positive). Excluding patients with accepted main risk factors, APA were positive in 15.3% of 85 patients. Conclusion: The high APA prevalence confirms its relevance in ocular occlusive disorders.

Detection of retinal dysfunction in vitelliform macular dystrophy using the multifocal ERG (MF-ERG).

Vitelliform macular dystrophy (VMD) is widely known for an abnormal EOG in the presence of a normal ERG. In this study the multifocal electroretinogram (MF-ERG) is described as an additional tool to detect retinal dysfunction in VMD. Three patients aged 30, 37 and 59 years with VMD and a visual acuity of OD: 0.4; OS 0.05 (patient 1), 1.25 OU (patient 2) and OU: 0.6 (patient 3) underwent additional electrophysiological testing with the MF-ERG. A multifocal-ERG of the central 50 degrees of the retina was obtained using the VERIS ™-system. During recording 103 hexagons flickered according to a binary m-sequence of 215. Mean luminance was 100 cd/m2, contrast was set at 99%. The MF-ERG recordings were compared to age matched control groups. In all three patients the MF-ERG of the central 6 degrees showed reduced amplitudes for N1P1 (first negative peak to first positive peak) and for P1N2 (P1 to the second negative peak). Implicit times were not affected. Therefore the MF-ERG can detect focal retinal dysfunction in VMD which would not be apparent in the summed retinal response recorded with the ganzfeld ERG. In contrast to other diseases, amplitudes rather than implicit times seem to be affected in the MF-ERG of vitelliform macular dystrophy.