[Long-term experiences with corneal crosslinking in patients with progressive keratoconus at the University Eye Hospital in Tübingen, Germany]. / Langzeiterfahrungen des kornealen Crosslinkings bei Patienten mit progredientem Keratokonus an der Universitäts-Augenklinik Tübingen.

BACKGROUND AND PURPOSE: The corneal collagen crosslinking procedure has been clinically performed worldwide for approximately 20 years. The aim of the study was to analyze the long-term outcomes of corneal crosslinking at the University Eye Hospital in Tübingen. METHODS: In this retrospective study 136 consecutive eyes with progressive keratoconus from 107 patients were included. The observational period was from December 2008 to March 2018. The parameters analyzed were best corrected visual acuity (BCVA) and the keratometry values from elevation maps measured using a Scheimpflug camera. RESULTS: The study population of 107 patients included 96 (90%) male and 11 (10%) female subjects and the mean age was 23 ± 8 years. The mean observation time between corneal collagen crosslinking and the last follow-up examination was 42 ± 29 months. The mean postoperative BCVA showed a significant improvement from baseline at each point of postoperative measurement. The mean astigmatism and the mean Kmax showed a statistically significant reduction in the first 6 postoperative months. The mean thinnest point of the cornea showed a significant reduction in the first 6 months, after which the cornea thickness stabilized. No serious adverse events relating to the treatment were registered. CONCLUSION: Long-term outcomes after corneal collagen crosslinking showed a significant reduction of the keratometry values and the BCVA was significantly higher compared to the preoperative value at all times of observation. In conclusion, corneal collagen crosslinking was shown to be an effective and safe treatment for progressive keratoconus.

Risk factors for and management of anterior chamber intravitreal dexamethasone implant migration.

BACKGROUND: This study aimed to investigate the incidence of and risk factors for the anterior chamber migration of an intravitreal dexamethasone implant (Ozurdex®). METHODS: A retrospective review of 640 consecutive intravitreal dexamethasone implant injections was conducted from February 2011 through February 2018 at the University Eye Hospital in Tübingen, Germany. Those patients who experienced anterior chamber dexamethasone implant migrations were identified, as well as the reasons for the anterior chamber migration. The surgical histories were obtained and comprehensive ophthalmic examinations were conducted for all of the eyes. Cross-tabulations, chi-squared tests, and Fisher's exact tests were used to assess the influences of different factors on the anterior chamber implant migrations. RESULTS: Overall, 4 eyes of four patients (0.63%) showed anterior chamber implant migrations. All four of the eyes were pseudophakic, and they had undergone prior vitrectomies. Three eyes had sclerally-fixated intraocular lenses, and one eye had a posterior chamber intraocular lens in the capsular bag, with a capsular tension ring due to partial zonular dehiscence. When comparing the vitrectomized eyes with reduced zonular/capsular bag complex integrity to the vitrectomized pseudophakic eyes with intact zonular/capsular bags, the former were significantly associated with an increased risk of anterior chamber implant migration (P = 0.008). The vitrectomized pseudophakic eyes, in contrast to the nonvitrectomized pseudophakic eyes, were significantly associated with an increased risk of anterior chamber implant migration (P = 0.009). CONCLUSIONS: The anterior chamber migration of an intravitreal dexamethasone implant is a serious complication. To minimize the risk of permanent corneal edema, immediate removal of the implant with a 20-gauge alligator forceps over a 2.75-mm long clear corneal tunnel is important. Those patients with insufficient zonular support, defects, or missing posterior capsular membranes and vitrectomy histories present a high risk of anterior chamber dexamethasone implant migration.

Establishment of a retinal hypoxia organ culture model.

Hypoxia plays an important role in several retinal diseases, especially in central retinal artery occlusion (CRAO). Although CRAO has been known for over a hundred years, no cure or sufficient treatment is available. Potential therapies are being evaluated in several in vivo models or primary cultures. However, in vivo models or primary cultures are very time-consuming, expensive, and furthermore several therapies or agents cannot be tested. Therefore, we aimed to develop a standardized organotypic ex vivo retinal hypoxia model. A chamber was developed in which rat retinal explants were incubated for different hypoxia durations. Afterwards, the retinas were adjusted to normal air and incubated for 24, 48 or 72 h under standard conditions. To analyze the retinal explants, and in particular the retinal ganglion cells (RGC) immunohistology, western blot and optical coherence tomography (OCT) measurements were performed. To compare our model to a standardized degeneration model, additional retinal explants were treated with 0.5 and 1 mM glutamate. Depending on hypoxia duration and incubation time, the amount of RGCs decreased and accordingly, the amount of TUNEL-positive RGCs increased. Furthermore, ß-III-tubulin expression and retinal thickness significantly decreased with longer-lasting hypoxia. The reduction of RGCs induced by 75 min of hypoxia was comparable to the one of 1 mM glutamate treatment after 24 h (20.27% versus 19.69%) and 48 h (13.41% versus 14.41%) of incubation. We successfully established a cheap, standardized, easy-to-use organotypic culture model for retinal hypoxia. We selected 75 min of hypoxia for further studies, as approximately 50% of the RGC died compared to the control group after 48 h.

[Transcorneal electrical stimulation in primary open angle glaucoma]. / Transkorneale Elektrostimulation bei primärem Offenwinkelglaukom.

Recently, reports have been published on the effectiveness of electrical stimulation in patients and experimental animal models with neurodegenerative ocular diseases. Our study included 14 patients with primary open angle glaucoma (POAG), who were randomized into one of three groups with 0% (sham, n = 5), 66% (n = 5) or 150% (n = 4) of their individual electrical phosphene thresholds. Patients were treated with transcorneal electrical stimulation (TES) for 30 min once a week for 6 consecutive weeks. Outcome measures of our study were the detection of possible adverse events and efficacy of TES using DTL electrodes in subjective and objective parameters of visual function under treatment. TES was tolerated well and no serious adverse events were registered relating to the treatment. One single adverse event was registered as appearance of an optic disc hemorrhage of a sham-stimulated eye. In summary, one significant increase of intra-ocular pressure in the 66% group was observed in comparison to the sham group (p = 0.04), without significant differences compared to the 150% group (both sham vs. 150% group and 66% vs. 150% group). This difference (mean difference compared to baseline of -2.33 mm Hg for the sham group and +0.97 mm Hg for the 66% group; REML) was not clinical meaningful. All other findings, including results of the visual field, were not statistically significant different between groups. It was shown that TES using DTL electrodes did not trigger adverse or serious adverse events in the stimulated groups in patients with POAG. Patients with POAG should currently receive TES only under study conditions.

Transfer characteristics of subretinal visual implants: corneally recorded implant responses.

PURPOSE: The subretinal Alpha IMS visual implant is a CE-approved medical device for restoration of visual functions in blind patients with end-stage outer retina degeneration. We present a method to test the function of the implant objectively in vivo using standard electroretinographic equipment and to assess the devices' parameter range for an optimal perception. METHODS: Subretinal implant Alpha IMS (Retina Implant AG, Reutlingen, Germany) consists of 1500 photodiode-amplifier-electrode units and is implanted surgically into the subretinal space in blind retinitis pigmentosa patients. The voltages that regulate the amplifiers' sensitivity (V gl) and gain (V bias), related to the perception of contrast and brightness, respectively, are adjusted manually on a handheld power supply device. Corneally recorded implant responses (CRIR) to full-field illumination with long duration flashes in various implant settings for brightness gain (V bias) and amplifiers' sensitivity (V gl) are measured using electroretinographic setup with a Ganzfeld bowl in a protocol of increasing stimulus luminances up to 1000 cd/m2. RESULTS: CRIRs are a meaningful tool for assessing the transfer characteristic curves of the electronic implant in vivo monitoring the implants' voltage output as a function of log luminance in a sigmoidal shape. Changing the amplifiers' sensitivity (V gl) shifts the curve left or right along the log luminance axis. Adjustment of the gain (V bias) changes the maximal output. Contrast perception is only possible within the luminance range of the increasing slope of the function. CONCLUSIONS: The technical function of subretinal visual implants can be measured objectively using a standard electroretinographic setup. CRIRs help the patient to optimise the perception by adjusting the gain and luminance range of the device and are a useful tool for clinicians to objectively assess the function of subretinal visual implants in vivo.

Factors that influence the suitability of human organ-cultured corneas.

PURPOSE: The purpose was to assess the influence of donor and storage factors on the suitability of organ-cultured corneas for transplantation. METHODS: Data from 1340 donor corneas stored between 2009 and 2015 were analyzed retrospectively. Logistic regression analysis was used to assess the influence of different factors on the suitability of grafts for transplantation. RESULTS: Forty-one percent (553/1340) of corneas were discarded. The leading causes were medical contraindication (20.2 %) and poor endothelial quality (19.3 %). Donor age influenced suitability for transplantation significantly. Corneas from donors aged 80 years and older were more likely to be discarded because of endothelial insufficiency (P < 0.0001). The cause of donor death including infection and multiple organ dsyfunction syndrom (MODS) increased the risk of bacterial or fungal contamination during organ culture (P = 0.007 and P = 0.014, respectively). Prolonged time between death and enucleation was associated with an increased risk of unsuitability for transplantation (P < 0.0001). The amount of time between death and corneoscleral disc excision and duration of storage influenced the suitability for transplantation (P = 0.0007 and P < 0.0001, respectively). CONCLUSION: Donor age, cause of death, storage time, death to enucleation and death to disc excision times influenced transplantation suitability. The percentage of discarded corneas may be reduced by shortening storage time, death to enucleation, and death to corneoscleral disc excision times. Setting a maximum donor age could reduce the percentage of discarded corneas. However, as long as there is a lack of donor corneas, we do not recommend any donor age limit.

[Immunotherapy of uveal melanoma: vaccination against cancer. Multicenter adjuvant phase 3 vaccination study using dendritic cells laden with tumor RNA for large newly diagnosed uveal melanoma]. / Immuntherapie beim Aderhautmelanom: Vakzination gegen Krebs. Multizentrische adjuvante Phase-III-Impfstudie mit Tumor-RNA-beladenen dendritischen Zellen bei neu diagnostizierten, großen Uveamelanomen.

Uveal melanomas are the most common malignant tumors of the eye. With modern molecular biological diagnostic methods, such as chromosome 3 typing and gene expression analysis, these tumors can be categorized into highly aggressive (monosomy 3, class II) and less aggressive forms. This molecular biological stratification is primarily important for determining the risk of these tumors as no therapy is currently available that is able to prevent or delay metastases. A randomized study of patients with a poor prognosis (monosomy 3) is currently being carried out in order to determine whether a cancer vaccine prepared from autologous (patient's own) dendritic cells and uveal melanoma RNA can prevent or delay progression and further metastases of this extremely aggressive form of cancer. Inclusion in the uveal melanoma study, which hopes to provide a potential therapeutic option for patients, is only possible if patients are referred to an institution that is able to manufacture and provide this vaccination before the patient is operated on or treated with radiation. Untreated tumor material is necessary for producing the vaccine on an individualized patient basis.

[Ocular electrical stimulation: Therapeutic application and active retinal implants for hereditary retinal degenerations]. / Okuläre elektrische Stimulation : Therapeutische Anwendung und aktive retinale Implantate bei hereditären Netzhautdegenerationen.

BACKGROUND: Electrical stimulation has a long history in ophthalmology. Subthreshold electrical stimulation can have beneficial therapeutic effects on hereditary degenerative retinal diseases. Suprathreshold stimulation is able to elicit visual perceptions and, if multielectrode fields are arranged as an array, usable pictures can be perceived by blind patients. OBJECTIVES: This is a review article on the current situation and studies on therapeutic transcorneal electrical stimulation. Moreover, the challenges, surgical concepts and visual results of active retinal implants are discussed. MATERIAL AND METHODS: This article gives an overview on transcorneal electrical stimulation and active retinal implants based on published results, with special emphasis on the clinical application. RESULTS: The results of initial controlled studies on therapeutic transcorneal electrical stimulation in hereditary retinal diseases were very promising. The largest controlled study so far in patients with retinitis pigmentosa (RP) has yielded many positive trends and some significant improvements in electrophysiological data. Currently, two retinal implants have regulatory approval, the Argus II retinal prosthesis system® (SecondSight®) and the Alpha-IMS© (Retina Implant AG). Both systems can be used to improve visual perception and under test conditions can achieve visual acuities of 0.02 and 0.04, respectively. CONCLUSION: In-depth analyses and follow-up studies in larger patient groups are currently planned to definitively clarify the potential of therapeutic transcorneal electrical stimulation in RP patients. The challenges of currently available active retinal implants are the technical biostability and the limited spatial resolution.

Causes that influence the detachment rate after Descemet membrane endothelial keratoplasty.

PURPOSE: To investigate Descemet graft (DG) detachment rate after Descemet membrane endothelial keratoplasty (DMEK) in relation to DG position. METHODS: A total of 175 consecutive pseudophakic eyes that underwent DMEK (175 eyes for Fuchs endothelial dystrophy) from September 2009 through February 2014 at the Tübingen Eye Hospital DG position were studied retrospectively by surgical video at the end of an operation. A group of 45 eyes showed a decentration of the DG with a stromal gap of ≥1.5 mm over at least 3 clock hours between the descematorhexis edge and the DG. DG detachment was documented at a mean follow-up of 13.9 ± 3.7 months after surgery. DG detachment was defined as a detachment of 20 % or more of the DG surface area. Various donor characteristics and patient characteristics were analyzed. RESULTS: The best spectacle-corrected visual acuity (BCVA) in the group of eyes with central well-positioned DG differed significantly from those of eyes with decentered DG. The preoperative BCVA in the central well-positioned DG group was 0.63 ± 0.40 logMAR, and in the decentered DG group 0.91 ± 0.51 logMAR (P < 0.001). The postoperative BCVA in the group of eyes with central well-positioned DG was 0.12 ± 0.11 logMAR, and in the group with decentered DG 0.23 ± 0.29 logMAR (P < 0.001). Endothelial cell density and patient characteristics such as age, gender, and intraocular pressure did not differ significantly between the two groups. The group of eyes with central well-positioned DG showed DG detachment in 12 %; the group with decentered DG findings had DG detachment in 87 % (P < 0.001) at the 12 month follow up. CONCLUSION: The present findings demonstrate the importance of central well-positioned DG and the relation of disease severity. Central well-positioned DG may reduce the incidence of DG detachment. Overlapping of the donor DG and the host Descemet membrane seems to be responsible for DG detachment. One possible way to enhance graft adhesion could be a larger descematorhexis, which avoids an overlapping. The second possible way could be not waiting too long for surgery to reduce disease severity.

[Diagnostics and treatment of choroidal lymphoma]. / Diagnostik und Therapie der choroidalen Lymphome.

Choroidal lymphoma is a rare disease and can be classified into primary and secondary choroidal lymphomas. Primary choroidal lymphoma is a low-grade extranodal marginal zone B-cell lymphoma and secondary choroidal lymphomas present ocular manifestations of disseminated systemic lymphomas. Typical clinical features of choroidal lymphoma are multifocal, yellow-whitish choroidal infiltrates. The vitreous body is usually clear and cell-free. Choroidal lymphoma has a tendency to extend through the sclera. In contrast to primary choroidal lymphoma, which is more often unilateral, does not show signs of anterior segment involvement and has a slow progression, secondary choroidal lymphoma is more often bilateral, has a rapidly progressive course with anterior segment and vitreous involvement and belongs to the high-grade lymphomas. The definitive diagnosis of choroidal lymphoma can only be confirmed by histopathological examination of biopsy tissue. The choroidal biopsy is the gold standard in the diagnostics of choroidal lymphoma. To date, no standardized treatment for choroidal lymphoma has been established. The treatment modalities include external beam radiotherapy, immunotherapy with rituximab and chemotherapy. The prognosis for survival of primary choroidal lymphoma is usually good. The prognosis of secondary choroidal lymphoma depends on the malignancy grade of systemic lymphoma.

[Using intracameral cefuroxime reduces postoperative endophthalmitis rate: 5 years experience at the University Eye Hospital Tübingen]. / 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.

The influence of axial length on confocal scanning laser ophthalmoscopy and spectral-domain optical coherence tomography size measurements: a pilot study.

PURPOSE: To investigate the influence of axial length on SD-OCT and cSLO size measurements from the Heidelberg Spectralis. METHODS: In this pilot study, eight emmetropic pseudophakic eyes with subretinal visual implant were selected. 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. The known size of subretinal implant sensor field (2800 × 2800 µm) was measured on 15 images per eye with cSLO and SD-OCT. 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 respectively. We found in short eyes, in medium eyes and in long eyes a mean value of sensor field size measurements from cSLO of 3327 ± 9 µm, 2800 ± 9 µm and 2589 ± 12 µm and from SD-OCT of 3328 ± 9 µm, 2800 ± 12 µm and 2585 ± 19 µm respectively. The size measurements decreased in SD-OCT and cSLO measurements with longer axial lengths significantly (p < 0.0001). CONCLUSION: The present findings demonstrate accuracy of the scaling in cSLO and SD-OCT measurements of the Heidelberg Spectralis for emmetropic medium eyes. The size measurements from SD-OCT to those from cSLO were approximately equal. Caution is recommended when comparing the measured values of short and long eyes with the normative database of the instrument. Further studies with larger sample sizes are needed to confirm findings.