Christian Ohrloff

High prevalence of resistance to APC in young patients with retinal vein occlusion.

Abstract. Resistance to activated protein C (APC) is among the coagulation disorders that have been implicated in retinal vein occlusion. However, since retinal vascular occlusions may be due to a combination of several mechanisms, the question of whether thrombophilic anomalies are pathogenic for this disorder remains controversial. In the current study, we investigated the prevalence of APC resistance in patients with retinal vein occlusion with reference to age and various cardiovascular risk factors. A cohort of 142 consecutive patients with retinal vein occlusion and a control group of 128 subjects matched for age, sex and several risk factors were screened for resistance to APC. Both cohorts were divided into two subgroups, according to the patients age (≤45 or >45 years) at the time of the retinal vein occlusion or a previous thromboembolic event. The proportion of individuals with resistance to APC was higher in the patient group (13 of 142; 9.1%) when compared to controls (6 of 128; 4.7%). Moreover, patient age ≤45 years by the time of the retinal vein occlusion or a previous thromboembolic event was significantly associated with a high prevalence of APC resistance (17%). By contrast, resistance to APC was present in 5 of 95 cases (5.3%) in the patient group >45 years and in 4 of 83 (4.8%) young controls. Our results indicate that APC resistance is highly prevalent in patients with retinal vein occlusion at age ≤45 years and/or with a history of thrombosis at this age. By contrast, the prevalence of APC resistance in patients who suffered a retinal vein occlusion when they were older than 45 years and had no history of thromboembolism appears to be similar to that seen in healthy control subjects or in the normal population. Selective screening may be helpful in identifying retinal vein occlusion patients with thrombophilic defects.

Fibrinolytic Therapy with Low-Dose Recombinant Tissue Plasminogen Activator in Retinal Vein Occlusion

Fibrinolytic therapy aimed at early restoration of blood flow appears to be a promising therapeutic approach in haemorrhagic retinopathy. The risk of bleeding complications, a major problem with fibrinolysis, can be reduced by the use of low-dose thrombolytic regimens. In our study, 14 patients with ischaemic central (CRVO) or branch (BRVO) retinal vein occlusion who presented with severe visual loss and recent onset of symptoms were treated with a low dose (50 mg) of recombinant tissue plasminogen activator (rt-PA) and intravenous heparin. In 10 of 14 patients (7 CRVO, 3 BRVO), an increase in visual acuity of one line or more on the logarithmic visual acuity chart was noted and in 8 patients (6 CRVO, 2 BRVO) a reduction of areas of capillary non-perfusion was observed, suggesting that a restoration of retinal capillary blood flow can be achieved if fibrinolysis is initiated in the early phase of haemorrhagic retinopathy. In view of the poor prognosis in the natural course of haemorrhagic retinopathy and the potential haemorrhagic risk in fibrinolysis, the use of low-dose rt-PA appears to constitute an encouraging approach in the management of this disease.

Visual Outcome after Treatment with Low-Dose Recombinant Tissue Plasminogen Activator or Hemodilution in Ischemic Central Retinal Vein Occlusion

The ischemic type of central retinal vein occlusion (CRVO) is associated with a poor visual and ocular prognosis. Although several reports have indicated that hemodilution or thrombolytic therapy may be of benefit, there is still no consensus among ophthalmologists about the management of this disorder. In our study, we retrospectively evaluated the visual outcome after medical treatment in 58 patients with ischemic CRVO and severe visual loss (≤20/50). We separately investigated three different groups, depending on the following criteria: onset of symptoms within 11 days prior to admission and thrombolytic treatment with 50 mg of recombinant tissue plasminogen activator (rtPA) and intravenous heparinization (n = 23) or hemodilution therapy (n = 22) or onset of symptoms >11 days before the initial visit and hemodilution (n = 13). An advancement of 2 or more lines on the logarithmic visual acuity chart was noted in 10 cases (44%) in the rtPA group and in 3 subjects (14%) in the early-phase hemodilution group, whereas only 1 patient in the late-phase hemodilution group showed a comparable improvement. Our findings suggest that treatment with low-dose rtPA or hemodilution aimed at early restoration of blood flow has the potential to improve the visual prognosis in ischemic CRVO. The finding that thrombolysis had a favorable outcome supports the hypothesis that specific subgroups of patients may benefit from this therapeutic approach. Further investigation will be required to definitively prove the effectiveness of fibrinolytic agents.

Detection of Inducible Nitric Oxide Synthase and Vascular Endothelial Growth Factor in Choroidal Neovascular Membranes

Vascular endothelial growth factor (VEGF) is among the cytokines which have been implicated in the pathogenesis of choroidal neovascularization secondary to age-related macular degeneration (ARMD). There is, however, evidence that intercellular signaling molecules, such as nitric oxide (NO), are involved in this process. NO is synthesized via the inducible isoform of NO synthase (iNOS), which is expressed after induction by cytokines. In the current study, we investigated whether VEGF and iNOS are coexpressed in choroidal neovascular membranes (n = 7) from patients with ARMD. Immunohistochemistry was performed on cryosections with anti-iNOS and anti-VEGF. Moderate to intense immunostaining for iNOS and VEGF was observed in retinal pigment epithelial cells, macrophages, and in spatial relation to vessel walls. As scored by light microscopy, we found a significant correlation between immunoreactivity for VEGF and iNOS (p < 0.0341) in vascular endothelial cells. Our study supports a significant role for iNOS in the pathogenesis of neovascularization and membrane growth in ARMD. Moreover, our findings suggest a possible relationship between NO and VEGF in the regulation of pathologic angiogenesis in this disease.

Visual improvement during psychophysical training in an adult amblyopic eye following visual loss in the contralateral eye

BackgroundRecent publications have demonstrated neural plasticity in adult amblyopes subjected to psychophysical training based on perceptual learning. The purpose of this case report is to present rarely available prospective data of visual acuity development in a strabismic amblyope undergoing psychophysical training and pleoptic treatment after loss of function of the non-amblyopic eye.MethodsThe design is a prospective, observational and interventional case report. Visual acuity was tested monthly, with constant optical correction. The 60-year-old female patient participated in a psychophysical training implemented in our laboratory, and in pleoptic treatment.ResultsSlow functional improvement of the amblyopic eye was observed during a period of 10 months, both in the tests used for training and in visual acuity: single optotypes increased by 4 chart lines, crowded optotypes by 2–3 lines.ConclusionsTo our knowledge, this is the first report of the new approach of perceptual learning in an adult amblyope after loss of vision in the contralateral eye. Our results represent further evidence that the visual system of adult amblyopes preserves a certain degree of neural plasticity, whether spontaneous or enhanced by training. Furthermore, that plasticity in adults is limited, and early diagnosis and treatment of amblyopia must remain the primary goal.

Retinal vein occlusion and low-dose fibrinolytic therapy (R.O.L.F.): a prospective, randomized, controlled multicenter study of low-dose recombinant tissue plasminogen activator versus hemodilution in retinal vein occlusion.

Purpose: To investigate the efficacy of intravenous thrombolysis with low-dose recombinant tissue plasminogen activator (rt-PA) in recent-onset central retinal vein occlusion (CRVO) or branch retinal vein occlusion. Methods: This was a prospective, randomized, controlled multicenter trial in patients with CRVO or branch retinal vein occlusion, best-corrected visual acuity ≤20/50, and onset of symptoms within 11 days before treatment. In each group, patients were randomized to either hemodilution or thrombolysis with 50 mg of rt-PA with concomitant intravenous heparinization. The primary clinical outcome measure was improvement in best-corrected visual acuity from baseline at 1 year. Results: Fifty-two subjects were enrolled in the study. Patients with CRVO (n = 41) who were treated with rt-PA exhibited a significant improvement in best-corrected visual acuity compared with those who received hemodilution (P < 0.0001). At 1-year follow-up, the proportion of eyes with CRVO achieving an improvement in visual acuity of three or more lines was 45% after treatment with rt-PA and 21% after hemodilution therapy. The median final best-corrected visual acuity among CRVO patients given rt-PA was 20/60 (light perception, 20/15) compared with 20/400 (light perception, 20/20) in the hemodilution group. There were no significant differences among patients with branch retinal vein occlusion (n = 11). We observed no serious adverse events. No significant differences were found regarding the development of ocular neovascularization. Conclusion: Treatment with intravenous low-dose rt-PA improved visual outcome in CRVO. Thrombolysis was not associated with a lower risk of ocular neovascularization, indicating that the mechanisms involved in this process occur at an early stage.

LASIK mit superiorem Hinge und Scanning-Spot-Excimerlaserablation zur Korrektur von Myopie und myopem Astigmatismus: Einjahresergebnisse einer prospektiven klinischen Studie an 100 Augen

ZusammenfassungHintergrund. In den letzten Jahren wird die Laser-in-situ-Keratomileusis (LASIK) vermehrt zur Korrektur von Fehlsichtigkeiten eingesetzt. Ziel der vorliegenden Auswertung war es, Sicherheit, Wirksamkeit, Vorhersagbarkeit, Stabilität sowie die Komplikationen der LASIK mit Scanning-Spot-Excimer-Technologie zu bewerten. Patienten und Methode. Hundert konsekutive LASIK-Operationen im Zeitraum zwischen 2/1998 und 2/1999 [60 Patienten im mittleren Alter von 37 Jahren (Spannbreite: 20–55 Jahre)] wurden ausgewertet. Als Schnittgerät für die Keratomileusis wurde das Hansatome™ Mikrokeratom mit superiorem Hinge eingesetzt (Flapdurchmesser: 9,5 mm), die Laserablation wurde mit einem Scanning-Spot-Excimerlaser (Technolas-C-Lasik-217) durchgeführt. Das sphärische Äquivalent der subjektiven manifesten Refraktion lag im Mittel bei −6,96±2,87 dpt, die mittlere Sphäre bei −6,47±2,71 dpt, der mittlere Astigmatismus bei −0,98±0,94 dpt. Vor der Behandlung erreichten 6% der Augen mit bester Korrektur nur einen Visus von 0,5. Kontrolluntersuchungen fanden präoperativ, nach 1 und 7 Tagen sowie nach 1, 4 und 12 Monaten statt. Sicherheit, Wirksamkeit, Vorhersagbarkeit, Stabilität der refraktiven Werte sowie die Komplikationen wurden mit der Datagraph-Software (Version 1.11) ausgewertet. Ergebnisse. Am ersten postoperativen Tag und nach einer Woche konnten alle 100 Augen nachuntersucht werden, nach einem Monat 96, nach vier Monaten 95 und nach einem Jahr 92 Augen. Nach einem Jahr verlor kein Auge zwei oder mehr Zeilen an Sehvermögen, 99% lagen im Bereich von ±1 Zeile und 1% gewann 2 Zeilen (Sicherheitsindex: 1,03). Es erreichten 92% aller Augen einen unkorrigierten Visus von ≥0,5, 77% ≥0,8 und 51% von ≥1,0 (Wirksamkeitsindex: 0,89); 60 Augen (65,21%) lagen im Bereich von ±0,5 dpt, 82 Augen (89,13%) im Bereich von ±1,0 dpt und 91 Augen (98,91%) im Bereich von ±2,0 dpt. Das mittlere sphärische Äquivalent betrug nach einem Jahr −0,15±1,31 dpt. Zwischen 1 und 12 Monaten zeigte sich eine mittlere Regression von −0,14 dpt. Auf Wunsch der Patienten wurden 5 Augen während der Studienperiode wegen Unter- oder Überkorrektur nachbehandelt. Schnittkomplikationen traten nicht auf. Hornhautinfektionen wurden nicht verzeichnet, eine diffuse lamelläre Keratitis (DLK) wurde 12-mal beobachtet, aber alle Fälle heilten komplikationslos ab. Bei 7 Augen kam es zu einer leichten Dezentrierung (<1 mm) der Ablation, die in einem Fall zu einer erhöhten Blendempfindlichkeit führte. Schlussfolgerung. Die LASIK-Operation mit superiorem Hinge und Scanning-Spot-Excimer-Photoablation ist zur refraktiven Behandlung von Myopie (bis maximal −12 dpt) und myopischem Astigmatismus (bis maximal −5 dpt cyl.) geeignet. Die refraktiven Ergebnisse zeigten über den Verlauf des 12-monatigen Untersuchungszeitraums hohe Stabilität. Die Vorhersagbarkeit der refraktiven Ergebnisse lässt sich weiter verbessern.AbstractPurpose. Recently laser-in-situ-keratomileusis (LASIK) has been increasingly used to correct refractive errors. The purpose of this investigation was to evaluate the safety, efficacy, predictability, stability and complications using the scanning spot excimer LASIK technology. Patients and methods. The results of 100 consecutive LASIK operations carried out between 2/1998 and 2/1999 on 60 patients (mean age 37 years, range 20–55 years) have been evaluated. The Hansatome™ microkeratome with a superior hinge (flap diameter: 9.5 mm) and a scanning spot excimer laser (Technolas C-Lasik 217) were used in all cases. The mean spherical equivalent of the subjective manifest refraction was −6.96±2.87 diopters (D), the mean sphere was −6.47±2.71 D and the mean astigmatism was −0.98±0.94 D. In 6% of the eyes preoperative visual acuity was not better than 20/40. Examinations were performed preoperatively, after 1 and 7 days, after 1, 4 and 12 months. Safety, efficacy, predictability, stability and complications were calculated using the datagraph software (version 1.11). Results. All 100 eyes were examined after 1 day and 1 week, 96 after 1 month, 95 after 4 months and 92 after 1 year. Following 1 year none of the eyes lost 2 or more lines of best corrected visual acuity, 99% were within ±1 line and 1% gained 2 lines (safety index 1.03). In 92% of all eyes an uncorrected visual acuity of ≥0.5 was reached, in 77% ≥0.8 and in 51% ≥1.0 (efficacy index 0.89). For 60 eyes (65.21%) a refractive correction of±0.5 D was necessary, for 82 eyes (89.13%) ±1.0 D and for 91 eyes (98.91%) ±2.0 D. The mean spherical equivalent after 1 year was −0.15±1.31 D. Between 1 and 12 months a mean regression of −0.14 D occurred. On the request of the patients, 5 eyes were retreated during the study period for under- or overcorrection. Complications due to the microkeratome did not occur. Corneal infections were not observed, a diffuse lamellar keratitis (DLK) was seen in 12 cases, but all cases healed with no loss of visual acuity. In 7 eyes a slight decentration of the ablation was observed using corneal topography, which in one case caused an increase in glare sensitivity. Conclusions. LASIK with superior hinge and scanning spot excimer photoablation is suitable for the correction of myopia (up to a maximum of −12 D) and for myopic astigmatism (up to a maximum of −5 D). The refractive results showed a high stability during the 12-month study period but there is still room for improvement of the predictability.

Cataract Surgery With Implantation of an Artificial Lens

BACKGROUND Cataract surgery, the most frequently performed operative procedure worldwide, typically concludes with the implantation of an artificial intraocular lens (IOL) to correct aphakia (absence of the crystalline lens). METHOD Selective literature review including current regulations, guidelines and recommendations for cataract surgery. RESULTS The main symptom of cataract is loss of visual acuity, which usually progresses slowly. It can arise in one eye or both. There is a basic distinction between congenital and acquired cataracts. The probability of developing a cataract rises with age because of biochemical aging processes. The development of a cataract becomes highly likely from the sixth decade of life onward. CONCLUSIONS As no effective medications for cataract are available at present, its current standard treatment is the removal of the clouded lens. In industrialized countries, this is usually done with ultrasound (phacoemulsification), followed by the implantation of an IOL.

Complications after implantation of intraocular devices in patients with cytomegalovirus retinitis

Abstract  · Purpose: The authors report their surgical experience after sustained-release ganciclovir treatment, as well as replacing empty ganciclovir implants in patients with acquired immune deficiency syndrome (AIDS) and cytomegalovirus (CMV) retinitis.  · Methods: Between November 1995 and August 1998, 79 eyes of 49 patients received 99 intravitreal ganciclovir implants. Patients were examined monthly after implant surgery. Follow-up periods ranged from 6 to 128 weeks.  · Results: At the first 3-week postoperative visit, 73 eyes (97.2%) of 46 patients exhibited stable conditions. In 6 eyes (3.8%) of 3 patients, further progression was noted due to resistance to ganciclovir. The most common early complication (within 6 weeks after implantation) was cystoid macular edema, observed in 7 eyes receiving implants. Retinal detachment was the most common late complication (over 6 weeks after implantation) in 11 eyes. In almost all eyes with CMV retinitis and retinal detachment, involvement of more than 25% of the retina was observed. Additional severe complications included extrusion of the first pellet in 2 eyes and cataract as a late complication in 5 eyes. A total of 28 eyes (35.4%) of 16 patients receiving a second implant did not experience significant three-line loss by the end of the follow-up period.  · Conclusion: In the treatment of CMV retinitis, sustained-release ganciclovir implantation seems to be an alternative to intravenous ganciclovir. Early implantation and additional replacement of the device has the potential to decrease the risk of developing retinal detachment. We would recommend additional systemic antiviral CMV therapy to avoid infection of the fellow eye and CMV disease.

Pigment-Epithelium-Derived Factor Is Upregulated in Photocoagulated Human Retinal Pigment Epithelial Cells

There is much evidence that pigment-epithelium-derived factor (PEDF) is a potent antiangiogenic cytokine which inhibits retinal and choroidal neovascularization by inducing apoptosis in activated vascular endothelial cells. Furthermore, the regulation of PEDF appears to be linked to the regulation of vascular endothelial growth factor (VEGF), one of the most potent inducers of intraocular neovascularization. Previous studies have established that thermal photocoagulation, the mainstay in the therapy of various neovascular diseases of the posterior segment, results in a decrease in intraocular concentrations of VEGF and other angiogenic growth factors, thereby inhibiting active retinal neovascularization. In the current study, we sought to determine whether thermal photocoagulation has the potential to regulate the expression of PEDF in human retinal pigment epithelial (RPE) cells. Cultures of RPE cells were photocoagulated with a 532-nm diode laser. Subsequently, RNA was isolated for RT-PCR, and whole-cell extracts and precipitated cell culture supernatant were subjected to Western blot analysis. According to our results, PEDF mRNA and protein are significantly upregulated after photocoagulation. Moreover, PEDF protein was found to be secreted in the cell culture medium.