[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.

Acute outcome of chronic total occlusion (CTO) recanalizsation in the elderly.

OBJECTIVES: Percutaneous coronary intervention (PCI) of total chronic total occlusion (CTO) still remains a major challenge in interventional cardiology. There is only insignificant knowledge reported in the literature about age differences in CTO recanalization. We analyzed in this study the issue of the impact of age on procedural characteristics, complications and short-term outcome. METHODS: Between 2012-2016 we included 440 patients. They underwent PCI for at least one CTO. Antegrade and retrograde CTO techniques were applied. The retrograde approach was used only after failed antegrade intervention. Continuous data are presented as the mean ± standard deviation; categorical data are presented as numbers and percentages unless otherwise specified. We used Twosamplet- t-test with equal variance to test the significant differences of the variables between the two cohorts. RESULTS: Procedural success proved independently of age. There was no significant interaction between age and procedural success (p=0.5). Complication rates were low in both groups (2.7% vs. 4%; p=0,4) with no difference in statistical significance. CONCLUSIONS: Our study suggests that in an aging society patients with severe coronary artery disease and chronical total occlusions an interventional therapy should be used more intensively. It can be performed safe and feasible.

Validity of the J-CTO Score and the CL-Score for predicting successful CTO recanalization.

BACKGROUND: Percutaneous coronary intervention (PCI) of total chronic coronary occlusion (CTO) still remains a major challenge in interventional cardiology. To predict the probability of a successful intervention different scoring systems are available. We analyzed in this study the validity of two scoring systems, the Japanese CTO score (J-CTO score) and the newly developed Clinical and Lesion-related score (CL Score). METHODS: Between 2012 and 2015 we included 379 consecutive patients. They underwent PCI for at least one CTO. Antegrade and retrograde CTO techniques were applied. The retrograde approach was used only after failed antegrade intervention. RESULTS: Patients undergoing CTO PCI were mainly men (84%). The overall procedural success rate was 84% (±0.4). The mean J-CTO score was 2.9 (±1.3) and the mean CL score was 4.3 (±1.7). The CL score predicted more precisely the interventional results than the J-CTO score. CONCLUSIONS: Our study suggests that the previously presented CL score is superior to the J-CTO score in identifying CTO lesions with a likelihood for successful recanalization. Generally it appears to be a helpful tool for selecting patients and identifying the appropriate operator.

[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.

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.

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.

[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.

[Refractive changes after Descemet membrane endothelial keratoplasty]. / Refraktionsänderung nach der Descemet-Membran-Endothelkeratoplastik.

Penetrating keratoplasty has different refractive disadvantages in contrast to posterior lamellar keratoplasty. For example, a decentered corneal trephination and a tilted trephination or unevenly tightened corneal sutures can cause an uncontrolled high astigmatism as well as a refractive change. Also the postoperative refraction may change over time as a result of wound healing, suture loosening or suture removal. The aim of this retrospective study was to investigate a possible refractive change after Descemet membrane endothelial keratoplasty (DMEK). A total of 139 pseudophakic eyes from 125 patients with endothelial decompensation had undergone DMEK surgery at the Tübingen Eye Clinic. After a mean postoperative time of 13.15 ± 2.98 months after DMEK discreet mean changes in the spherical equivalent of + 0.37 ± 0.87 diopters and the cylinder to - 0.45 ± 0.57 diopters were observed. The mean central corneal thickness decreased from 670 ± 70 µm to 544 ± 55 µm. In conclusion after DMEK a discreet induced hyperopic refractive shift due to the reversal of stromal swelling was observed.

[Management of corneal endothelial decompensation with Descemet's membrane endothelial keratoplasty in a patient with Ahmed glaucoma valve implant]. / Behandlung einer Endotheldekompensation mit der Descemet-Membran-Endothelkeratoplastik bei einem Patienten mit Ahmed-Implantat.

BACKGROUND: Currently, the main causes for developing bullous keratopathy are from problems related to intraocular surgery, trauma, infection, Fuchs' endothelial dystrophy and chronically elevated intraocular pressure. In the 1990s penetrating keratoplasty was once considered the therapy of choice for treatment of bullous keratopathy but in recent years it has been replaced by posterior lamellar keratoplasty. The Descemet membrane endothelial keratoplasty (DMEK) procedure represents the final development of posterior lamellar keratoplasty. The question now arises whether DMEK can be used in patients with bullous keratopathy and Ahmed glaucoma valve implant. CASE REPORT: A 72-year-old man was referred to our hospital for further evaluation with the diagnosis of bullous keratopathy and pseudoexfoliative glaucoma. The bullous keratopathy was caused by a variety of previous operations as well as decompensation of intraocular pressure. This article describes the therapy of bullous keratopathy by DMEK with existing Ahmed glaucoma valve implant. After surgery the cornea became clear and the best-corrected visual acuity improved from hand movement to 0.2. The intraocular pressure remained normal (10-14 mmHg) without antiglaucoma medication and the endothelial cell count decreased only slightly over a follow-up of 13 months. No complications were encountered. CONCLUSIONS: The DMEK surgical procedure seems to be possible in patients with Ahmed glaucoma valve implant and endothelial decompensation. However, further studies with a larger number of patients should follow to validate the replacement of penetrating keratoplasty and other posterior lamellar procedures by DMEK.

[Effects of transcorneal electrical stimulation in patients with Stargardt's disease]. / Transkorneale Elektrostimulation bei Patienten mit Morbus Stargardt.

Stargardt's 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 Stargardt's 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.

Effect of acute hyperhomocysteinemia on methylation potential of erythrocytes and on DNA methylation of lymphocytes in healthy male volunteers.

Homocysteine is a precursor of S-adenosylmethionine (AdoMet) and a metabolite of S-adenosylhomocysteine (AdoHcy). The ratio of AdoMet to AdoHcy, defined as the methylation potential (MP), indicates the flow of methyl groups within the cells. Chronic elevations of total homocysteine (tHcy) in plasma correlate with increased AdoHcy concentrations, decreased MP, and impaired DNA methylation. However, the influence of acute hyperhomocysteinemia on MP is unknown. We induced acute hyperhomocysteinemia in 14 healthy volunteers by oral administration of l-homocysteine (65.1 micromol/kg body wt) in an open, randomized, placebo-controlled two-period crossover study. The kinetics of tHcy in blood and urine, MP in blood, and global DNA methylation in lymphocytes were studied systematically during 48 h. Plasma tHcy concentrations reached a peak at 34 +/- 11 min after an oral load with l-homocysteine and decreased with a half-life of 257 +/- 41 min (means +/- SD). Only 2.3% of the homocysteine dose were recovered in urine. AdoHcy concentrations and MP in whole blood and erythrocytes were not affected by the oral homocysteine load. Furthermore, global DNA methylation in lymphocytes did not change under these conditions. We found no difference between the genotypes of 5,10-methylenetetrahydrofolate reductase in response to the homocysteine load. However, AdoMet content in erythrocytes was significantly higher in the C677T carriers (CT; n = 7) compared with the CC genotype (n = 7). Although chronic elevation of tHcy has been shown to affect MP and DNA methylation, acute elevation of plasma tHcy above 20 micromol/l for 8 h is not sufficient to change MP and to induce DNA hypomethylation in lymphocytes.

Inadvertent intravitreal gentamicin injection.

PURPOSE: To describe the management and consequences of an accidental injection of gentamicin in the vitreous. METHODS: A retinal detachment developed in a 70-year-old male. During a vitrectomy operation, gentamicin (20mg) was accidentally injected in to the eye. The surgeon immediately began vigorous lavage of the vitreal cavity with balanced salt solution. RESULTS: No toxic signs appeared after the operation, despite the devastating consequences described in previous reports. CONCLUSIONS: The immediate vigorous lavage may have reduced the concentration of the toxic material and its consequences.

Pulsatile ocular blood flow in diabetic retinopathy.

PURPOSE: To assess circulatory properties of eyes with progressive stages of diabetic retinopathy. METHODS: The intraocular pressure, pulse amplitude (PA) and pulsatile ocular blood flow (POBF) were measured with a pneumatonometer (OBF Labs UK Ltd). The eyes were grouped: (a) normal control, n = 26, (b) diabetes with no observable diabetic retinopathy (NDR), n = 18, (c) mild to moderate non-proliferative diabetic retinopathy (NPDR), n = 20, and (d) very severe pre-proliferative and proliferative diabetic retinopathy (PPDR/PDR), n = 12. RESULTS: The PA and POBF values were lower than normal values in the earliest stage (NDR). The POBF increased but was still below normal levels at the NPDR stage, and then increased to an above normal level in the PPDR/PDR stage of diabetic retinopathy. The PA was at normal levels in these later two stages. CONCLUSION: An initial decrease in pulsatile ocular blood flow is present with the onset of diabetes where no diabetic retinopathy has yet occurred. Subsequently, the pulsatile ocular blood flow increases with the severity of the retinopathy.

Total internal reflection of laser light in eyes filled with silicone oil.

BACKGROUND AND OBJECTIVES: This is the first report of clinical settings in which total internal reflection of laser light in eyes filled with silicone oil was observed. The authors analyze this phenomenon and outline the potential hazards it may present to patient, surgeon, and operating room personnel. MATERIALS AND METHODS: The authors observed significant reflection of laser light off the silicone-water interface both intraoperatively and in the clinic. The critical angle according to Snell's law (i.e., the angle at which total internal reflection occurs at the interface between silicone oil and vitreous) was calculated. The critical angle was found to be 71.9691 degrees(72 degrees). RESULTS: An analysis of each of the clinical conditions where this phenomenon was observed is presented. Clinical and surgical implications are discussed. CONCLUSIONS: The hazard of total internal reflection of laser light in eyes filled with silicone oil should be recognized by ophthalmologists to avoid possible complications. Techniques for overcoming and circumventing the difficulties resulting from this phenomenon are proposed.