Tobias Röck

Transcorneal Electrical Stimulation for Patients with Retinitis Pigmentosa: A Prospective, Randomized, Sham-Controlled Exploratory Study

PURPOSE To assess the safety of transcorneal electrical stimulation (TES) and explore its efficacy in various subjective and objective parameters of visual function in patients with retinitis pigmentosa (RP). METHODS Twenty-four patients in this prospective, randomized, partially blinded, good-clinical-practice study underwent TES (5-ms biphasic pulses; 20 Hz; DTL electrodes) 30 minutes per week for 6 consecutive weeks. The patients were randomly assigned to one of three groups: sham, 66%, or 150% of individual electrical phosphene threshold (EPT). Visual acuity (VA), visual field (VF; kinetic, static), electroretinography (Ganzfeld, multifocal), dark-adaptation (DA), color discrimination, and EPTs were assessed at all visits or four times, according to the study plan. RESULTS TES using DTL electrodes was tolerated well; all patients finished the study. Two adverse (foreign body sensation), but no serious adverse events were encountered. There was a tendency for most functional parameters to improve (8/18) or to remain constant (8/18) in the 150% group. VF area and scotopic b-wave amplitude reached statistical significance (P < 0.027 and P < 0.001, respectively). Only desaturated color discrimination and VF mean sensitivity decreased. There was no obvious trend in the 66% group. CONCLUSIONS TES was found to be safe in RP patients. Positive trends were discovered, but due to the small sample size of this exploratory study, statistical significance was reached only for VF area and scotopic b-wave amplitude. Further studies with larger sample sizes and longer duration are needed to confirm the findings and to define optimal stimulation parameters. (ClinicalTrials.gov number, NCT00804102.).

Gene expression profiling of the retina after transcorneal electrical stimulation in wild-type Brown Norway rats.

PURPOSE Transcorneal electrical stimulation (TES) has been beneficial in several neurodegenerative ocular diseases, but the exact mechanisms remain to be elucidated. This study was conducted to investigate the effects of TES on the retinas of wild-type Brown Norway (BN) rats by gene expression profiling and to assess its effects on retinal function and morphology. METHODS TES was applied to BN wild-type rat retinas in vivo for 1 hour (1-ms biphasic pulses at 20 Hz; 200 μA). RNA was isolated and processed for microarray-based profiling 4 hours after TES; differentially expressed genes from TES compared with those from sham-treated animals were validated by quantitative real-time polymerase chain reaction. Furthermore, the effect of TES was assessed at the structural and functional levels using electroretinography, confocal scanning laser ophthalmoscopy, optical coherence tomography, and immunohistochemistry. RESULTS Transcriptome changes associated with TES versus sham-stimulated BN wild-type retina were identified. Four hundred ninety genes were differentially expressed in TES and included potentially neuroprotective genes such as Bax or members of the tumor necrosis factor family (Tnfrsf11b, Tnrsf12a, Tnfsf13b, Tnfsf13). ERG recordings showed physiological retinal function after TES, and structural in vivo and ex vivo studies revealed intact retinal anatomy. CONCLUSIONS These results demonstrate that TES applied to the retina of the wild-type BN rats induces distinct transcriptome level changes and may help in the understanding of the mechanisms underlying TES. In addition, TES treatment indicates no negative effect on structure and function of the wild-type BN retina up to 35 hours after application.

Transcorneal electrical stimulation shows neuroprotective effects in retinas of light-exposed rats

PURPOSE To examine the effects of transcorneal electrical stimulation (TES) on retinal degeneration of light-exposed rats. METHODS Thirty-three Sprague Dawley albino rats were divided into three groups: STIM (n = 15) received 60 minutes of TES, whereas SHAM (n = 15) received identical sham stimulation 2 hours before exposure to bright light with 16,000 lux; healthy animals (n = 3) served as controls for histology. At baseline and weekly for 3 consecutive weeks, dark- and light-adapted electroretinography was used to assess retinal function. Analysis of the response versus luminance function retrieved the parameters Vmax (saturation amplitude) and k (luminance to reach ½Vmax). Retinal morphology was assessed by histology (hematoxylin-eosin [HE] staining; TUNEL assay) and immunohistochemistry (rhodopsin staining). RESULTS Vmax was higher in the STIM group compared with SHAM 1 week after light damage (mean intra-individual difference between groups 116.06 μV; P = 0.046). The b-wave implicit time for the rod response (0.01 cd.s/m²) was lower in the STIM group compared with the SHAM group 2 weeks after light damage (mean intra-individual difference between groups 5.78 ms; P = 0.023); no other significant differences were found. Histological analyses showed photoreceptor cell death (TUNEL and HE) in SHAM, most pronounced in the superior hemiretina. STIM showed complete outer nuclear layer thickness preservation, reduced photoreceptor cell death, and preserved outer segment length compared with SHAM (HE and rhodopsin). CONCLUSIONS This sham-controlled study shows that TES can protect retinal cells against mild light-induced degeneration in Sprague Dawley rats. These findings could help to establish TES as a treatment in human forms of retinal degenerative disease.

Phosphene thresholds elicited by transcorneal electrical stimulation in healthy subjects and patients with retinal diseases.

PURPOSE To evaluate electrically evoked phosphene thresholds (EPTs) in healthy subjects and in patients with retinal disease and to assess repeatability and possible correlations with common ophthalmologic tests. METHODS In all, 117 individuals participated: healthy subjects (n = 20) and patients with retinitis pigmentosa (RP, n = 30), Stargardts disease (STG, n = 14), retinal artery occlusion (RAO, n = 20), nonarteritic anterior ischemic optic neuropathy (NAION, n = 16), and primary open-angle glaucoma (POAG, n = 17). EPTs were determined at 3, 6, 9, 20, 40, 60, and 80 Hz with 5 + 5-ms biphasic current pulses using DTL electrodes. Subjects were examined twice (test-retest range: 1-6 weeks). An empirical model was developed to describe the current-frequency relationship of EPTs. Visual acuity, visual field (kinetic + static), electrophysiology (RP, RAO, STG: Ganzfeld-electroretinography [ERG]/multifocal-ERG; POAG: pattern-ERG; NAION: VEP), slit-lamp biomicroscopy, fundus examination, and tonometry were assessed. RESULTS EPTS varied between disease groups (20 HZ: healthy subjects: 0.062 ± 0.038 mA; STG: 0.102 ± 0.097 mA; POAG: 0.127 ± 0.09 mA; NAION: 0.244 ± 0.126 mA; RP: 0.371 ± 0.223 mA; RAO: 0.988 ± 1.142 mA). In all groups EPTs were lowest at 20 Hz. In patients with retinal diseases and across all frequencies EPTs were significantly higher than those in healthy subjects, except in STG at 20 Hz (P = 0.09) and 40 Hz (P = 0.17). Test-retest difference at 20 Hz was 0.006 mA in the healthy group and 0.003-0.04 mA in disease groups. CONCLUSIONS Considering the fast, safe, and reliable practicability of EPT testing, this test might be used more often under clinical circumstances. Determination of EPTs could be potentially useful in elucidation of the progress of ophthalmologic diseases, either in addition to standard clinical assessment or under conditions in which these standard tests cannot be used meaningfully. (ClinicalTrials.gov number, NCT00804102.).

Influence of Axial Length on Thickness Measurements Using Spectral-Domain Optical Coherence Tomography

PURPOSE The purpose of this study was to assess the influence of axial length on spectral-domain optical coherence tomography (SD-OCT) thickness measurements in patients with subretinal visual implants. METHODS Data from eight emmetropic pseudophakic eyes of eight patients with subretinal visual implants were analyzed retrospectively. These patients participated in the monocentric part of a multicenter trial. The axial length was measured in three short (<22.5 mm), three medium (22.51-25.50 mm), and two long (>25.52 mm) eyes. Using Heidelberg Spectralis, the known thickness of a subretinal implant microchip (70 μm) was measured on 15 images per eye with SD-OCT, using the software calipers. RESULTS The mean axial length was 20.8 ± 0.8 mm in short eyes, 23.3 ± 0.4 mm in medium eyes, and 26.3 ± 0.5 mm in long eyes. We found in short eyes, in medium eyes, and in long eyes a mean value of microchip thickness measurements from SD-OCT of 82.9 ± 1.4 μm, 70.5 ± 1.3 μm, and 64.2 ± 1.3 μm, respectively. The thickness measurements decreased in SD-OCT measurements with longer axial lengths significantly (P < 0.0001). CONCLUSIONS Axial length influences SD-OCT thickness measurements. Our findings demonstrate accuracy of the scaling in SD-OCT thickness measurements in emmetropic medium eyes. Caution is recommended when comparing the measured values of short and long eyes with the normative database of the instrument. There is a need for larger sample-size studies to confirm our results. (ClinicalTrials.gov number, NCT01024803.).

Evaluation of Factors Limiting Corneal Donation

BACKGROUND This study aimed to investigate factors limiting corneal donation at the University Hospital Tübingen. MATERIAL AND METHODS We retrospectively studied all hospital deaths from January 2012 to December 2015, considering each deceased patient as a potential corneal donor. During this period an ophthalmic resident managed corneal donor procurement on a full-time basis. Various factors limiting corneal donation were examined. RESULTS Among the 3412 deaths, 2937 (86.1%) displayed nonfulfillment of corneal donation. Consent for corneal donation was obtained in 475 cases (13.9%). The mean annual corneal donation rate was 13.9 donors per 100 deaths (range: 11.2-17.8). The leading causes of nonfulfillment of corneal donations were refusal to donate (49.8%, 1698 cases) and medical contraindications (23.6%, 805 cases). After next-of-kin interview of 2173 potential donors (109 potential donors were excluded because of logistical problems), willingness to participate in corneal donation was present in 475 cases (21.9%), whereas in 1698 cases (78.1%) corneal donation was refused. CONCLUSIONS Our study showed refusal to donate is the most important factor limiting corneal donation. It seems that increasing the knowledge of people about corneal donation through public education and media are necessary to address the corneal shortage.

Reduktion der postoperativen Endophthalmitisrate durch intrakamerale Cerfuroximgabe: Ergebnisse aus 5 Jahren Erfahrungen an der Universitäts-Augenklinik Tübingen

BACKGROUND Cataract surgery is the most commonly performed surgical procedure in developed countries. The annual number of cataract surgeries in Germany is about 600,000. Acute postoperative endophthalmitis is a very severe and the most dreaded complication of cataract surgery. Various operative and non-operative measures have been suggested to prevent this serious complication. The European Society of Cataract & Refractive Surgeons (ESCRS) study of intracameral cefuroxime was the first prospective, randomised and partially placebo-controlled clinical trial showing the efficacy of antibiotic prophylaxis to prevent endophthalmitis in 2007. The aim of this retrospective study is to investigate a possible reduction of intracameral cefuroxime to prevent postoperative endophthalmitis at the University Eye Hospital Tübingen. PATIENTS AND METHODS During the period from January 2002 to August 2013, 2 time periods were determined based on the adoption of intracameral cefuroxime injections after cataract surgery. From January 2002 to May 2009 patients received at the end of cataract surgery a subconjunctival administration of 50 mg of mezlocillin and postoperative antibiotic eye drops (gentamicin) without intracameral injection. From June 2009 to August 2013, patients received an intracameral injection of cefuroxime while antibiotic drops (moxifloxacin) were used too. The rates of postoperative infectious endophthalmitis during these 2 periods were calculated. RESULTS 31 cases of endophthalmitis occurred in 31,386 cataract surgeries. The overall cumulative incidence was 0.99 per 1000 patients. The incidence in the first period without intracameral cefuroxime injection was 1.38 (95 % confidence interval [CI]: 1.03-1.72) per 1000 patients and in the second period 0.44 (95 % CI: 0.34-0.54) per 1000 patients (p < 0.001). CONCLUSION Intracameral injection of cefuroxime reduces the rate of postoperative infectious endophthalmitis in cataract surgery significantly.

Descemet membrane endothelial keratoplasty in cases with existing scleral-sutured and iris-sutured intraocular lenses

BackgroundTo report two cases of Descemet Membrane Endothelial Keratoplasty (DMEK) in patients with existing scleral-fixated and iris-fixated intraocular lenses (sf-IOL and if-IOL, respectively).Case presentationDMEK procedures were performed on a 49-year-old woman with a pre-existing sf-IOL (case 1) and a 69-year-old woman with a pre-existing if-IOL (case 2) in order to treat secondary corneal edema due to pseudophakic bullous keratopathy. Visual acuity, refractive error, intraocular pressure, slit lamp examination, pachymetry measurements and endothelial cell density (ECD) were considered and repeated during follow-ups.Both cases had no intraoperative complications. At postoperative day 1 graft centration and complete attachment were noted. The IOL positions were unchanged in comparison to their preoperative positions. In case 1, visual acuity improved from 1/15 at 1 meter preoperative to 20/200 within one week and to 20/63 within 12 weeks of follow up. In case 2, visual acuity improved from counting fingers at 1 meter preoperative to 20/200 within one week and to 20/100 within 12 weeks of follow-up. In case 2 a partial graft dislocation was observed at postoperative day twenty. Complete graft re-apposition was achieved by rebubbling procedure performed with intracameral air injection.ConclusionsDMEK surgery in the treatment of pseudophakic bullous keratopathy in the presence of sf-IOL and if-IOL can successfully be performed. These eyes are at increased risk of IOL dislocation into the vitreous cavity during DMEK surgery.

Rates of and Experiences with Corneal Donation at the University Hospital Tübingen From 2002 To 2015

BACKGROUND This study aimed to report the rates and experiences of corneal donation at the University Hospital Tübingen. MATERIAL AND METHODS Data from all cornea donors from January 2002 to December 2015 were analyzed. The rates of corneal donation were examined. From 2002 to 2008, an ophthalmic resident handled the corneal donor procurement in addition to his ward work. From 2009 to 2015, an ophthalmic resident handled the corneal donor procurement on a full-time basis. RESULTS Among the 10 260 deaths, consent for corneal donation was obtained in 892 cases. The mean annual corneal donation rate was 8.7 donors per 100 deaths (range: 2.0-17.8). The mean corneal donation rate in the first period without a full-time ophthalmic resident in the eye bank team was 4.0 donors per 100 deaths (95 % confidence interval [CI]: 1.0-6.9) and in the second period 12.3 donors per 100 deaths (95 % CI: 3.2-21.5) (P<0.0001). Comparing the periods before and after the modification of the eye bank team, the corneal donation rate was increased by more than 3 times. CONCLUSIONS Our study showed the influence of the eye banking team on the corneal donation rate. Modification of the eye bank team, by recruiting a full-time resident at a University Hospital with 1500 beds, increased the corneal donation rate by more than 3 times. It appears necessary to strengthen this team with sufficient staff levels to improve donor rates.

Transkorneale Elektrostimulation bei Patienten mit Morbus Stargardt

Stargardts disease is an autosomal recessive inherited juvenile macular degeneration and at present no acknowledged science-based therapy is available for these patients. Recently, reports have been published on the effectiveness of electrical stimulation in experimental animal models and in patients with neurodegenerative ocular disease, particularly retinitis pigmentosa. This study included 12 patients with Stargardts disease who were randomized into one of three groups (n = 4) with 0% (sham), 66% or 150% of the individual electrically stimulated phosphene threshold. Outcome measures of the study were safety and efficacy of transcorneal electrical stimulation (TES) with DTL electrodes in subjective and objective parameters of visual function under therapy. In general TES was well tolerated and no adverse or serious events were noted. Neither Ganzfeld, multifocal ERG, OCT nor visual field testing showed statistically significant changes in any group.