The role of pigment epithelial detachment in AMD with submacular hemorrhage treated with vitrectomy and subretinal co-application of rtPA and anti-VEGF.

PURPOSE: To assess the incidence of pigment epithelial detachment (PED) in age-related macular degeneration (AMD) with submacular hemorrhage (SMH) and its response to treatment with pars plana vitrectomy (ppV), subretinal co-application of recombinant tissue plasminogen activator (rtPA) and anti-VEGF, and an intravitreal gas tamponade. METHODS: Consecutive interventional case series of 132 eyes of 129 patients with neovascular AMD with SMH. All eyes underwent ppV with subretinal co-application of rtPA and bevacizumab followed by a gas tamponade. Postoperatively, two additional intravitreal anti-VEGF injections were applied monthly, followed by intravitreal anti-VEGF injections applied PRN thereafter. PEDs and SMHs were evaluated with SD-OCT pre- and postoperatively. RESULTS: Preoperatively, 88 of 132 (67%) eyes were examined by OCT, and in 81 of these eyes the RPE could be visualised. A PED was found in 74 (91%) eyes, and no PED was found in five (6%) eyes. Median height of preoperative PED was 503 µm (range 150-1242, n = 65) and reduced to 344 (n = 62) and 306 µm (n = 27) after 3 and 12 months respectively. Two eyes showed a pre-existing rip of the RPE. Postoperatively, a rip was documented in 12 of 128 (9%) eyes. Median height of SMH was 762 µm (range 217-1840), median diameter was 4.3 (1.5-15) disc diameter. A complete displacement of the SMH from the fovea was achieved in 112 of 129 (87%) eyes. Overall, median best-corrected logMAR visual acuity (BCVA) improved significantly from preoperative 1.6 (0.5-2.0, n = 132) to 1.0 (0.2-2.0) 3 (n = 132) and 12 months (n = 74) postoperatively. Excluding eyes with pre-existing macular scars (n = 22), BCVA 3 months postoperatively was 0.8. Height of PED or SMH did not correlate with postoperatively BCVA, while size of SMH showed a mild correlation (rho = 0.25, p = 0.005). CONCLUSION: PpV with subretinal co-application of rtPA and bevacizumab and an intravitreal gas tamponade effectively displaces SMH and improves BCVA. Preoperatively, PED is found in the majority of eyes. Height of PED or SMH did not correlate with postoperatively BCVA. Tears of the RPE occur as frequently as in exudative AMD without SMH.

[Extensive yellowish fundus changes in a 6-year-old child]. / Großflächige gelbliche Fundusveränderungen bei 6­jährigem Kind.

We describe a 6-year-old, symptom-free girl presenting with a best corrected visual acuity of 0.6 on both eyes. Clinically we found yellowish subretinal lesions in the macula and around the vessel arcade without signs of vasculitis or abnormal vessels in the angiography. Fundus autofluorescence was marked and SD-OCT showed subretinal hyperreflective masses. With the help of molecular genetics we could make the diagnosis of an autosomal recessive bestrophinopathy (ARB). The natural history over 22 months revealed a slight recovery of the visual acuity as well as a slight reduction of the subretinal deposits.

[Screening for glaucoma by blue light-pattern ERG and OCT--are the methods comparable?]. / Glaukomscreening mit dem blaulicht-muster-ERG und dem OCT--sind beide verfahren gleichwertig?

BACKGROUND: Up to now, several examinations are necessary to identify early glaucoma. It is also possible to analyse the peripapillary retinal nerve fibre layer thickness by means of OCT. The loss of retinal ganglion cells can be measured by pattern ERG, therefore this method could be used for the detection of early glaucoma. This study compares the results of the blue light-pattern ERG with the Stratus OCT for glaucoma early recognition. PATIENTS AND METHODS: We studied 30 healthy test persons, 20 patients with glaucoma and 20 patients with suspected glaucoma. Each group was examined using eye pressure measurements, funduscopy, perimetry, pachymetry und analysing the retinal nerve fibre layer by the Stratus OCT. The diagnostic work-up was completed by the pattern ERG and an upgrade with a blue light filtering glass. The results of the blue light-pattern ERG and the OCT ("healthy" or "pathological") were compared in a cross table and the agreement between these two raters was measured by the Cohen's kappa coefficient. RESULTS: Pattern ERG and blue light-pattern ERG decrease with advancing age. After developing an age-matched calibration graph we defined standard values up to the age of 56 years. All included subjects were classified by Stratus OCT and blue light-pattern ERG as healthy. We recognised a significant reduction of the retinal nerve fibre layer thickness and the amplitude in the pattern ERG in the cluster of glaucoma patients. For most of them, a blue light-pattern ERG could not be recorded. Nine out of 40 glaucoma suspect eyes were judged as "pathological". Regarding the amplitudes of the blue light-pattern ERG 25 of 28 eyes under suspicion of glaucoma were assigned as "healthy". With the aid of the cross table we estimated a Cohen's kappa of 0.4. The sensitivity of the blue light-pattern ERG was computed to be 70 % and the specificity to be 97.7 %. For the OCT we calculated the sensitivity to be 50 % and the specificity to be 100 %. CONCLUSION: The blue light-pattern ERG correlates in 87 % of our cases with the OCT. Healthy test persons are certainly identified just as well as definitely glaucomatous patients. To distinguish people suspected of early glaucoma the blue light-pattern ERG can be used as an additional, fast and economic diagnostic procedure.

[Subretinal co-application of rtPA and bevacizumab for exudative AMD with submacular hemorrhage. Compatibility and clinical long-term results]. / Subretinale Koapplikation von rtPA und Bevacizumab bei exsudativer altersbedingter Makuladegeneration mit submakulärer Blutung. Kompatibilität der Wirkstoffe und klinische Langzeitergebnisse.

Exudative age-related macular degeneration (AMD) is the most frequent cause of acute submacular hemorrhage (SMH). Without treatment the formation of a macular scar with poor visual function is the usual outcome. While several surgical treatment approaches have been proposed to date, there is no general consensus regarding optimal treatment of acute SMH. Vitrectomy with subretinal co-application of recombinant tissue plasminogen activator (rtPA) and bevacizumab followed by a gas tamponade is a new approach which has shown promising functional results in clinical studies. The aim of the co-application of rtPA and bevacizumab is to simultaneously displace the submacular hemorrhage from the fovea and to effectively reduce choroidal new vessel activity. Experimental studies have shown that rtPA and bevacizumab are compatible in a co-application.

Vectorial release of matrix metalloproteinases (MMPs) from porcine RPE-choroid explants following selective retina therapy (SRT): towards slowing the macular ageing process.

The purpose of this study was to investigate release of matrix metalloproteinases (MMP) 2 and 9 during retinal pigment epithelium (RPE) wound healing after Selective Retina Therapy (SRT) with laser energy levels below and above the threshold of RPE cell death. Following exposure to SRT using a prototype pulsed Nd:YLF laser with energies of 80-180 mJ/cm(2) fresh porcine RPE-monolayers with Bruch's membrane and choroid were cultured in modified Ussing chambers which separate the apical (RPE-facing) and basal (choroid facing) sides of the RPE monolayer. Threshold energy for RPE cell death and wound healing were determined with calcein-AM viability test. Inactive and active forms of MMP 2 and 9 were quantified within tissue samples and in the culture medium of the apical and basal compartments of the Ussing chamber using gelatine zymography. Laser energies of 160-180 mJ/cm(2) resulted in cell death within 1 h while 120-140 mJ/cm(2) resulted in delayed death of exposed RPE cells. All cells survived 80 and 100 mJ/cm(2). Laser spots healed within 6 days after SRT accompanied by a transient vectorial increase of MMPs. SRT with 180 mJ/cm(2) increased active MMP 2 by 1.9 (p < 0.05) and 1.6 (p < 0.05) fold in tissue and basal compartments, respectively, without alterations in the apical compartment. Pro-MMP 2 levels were also significantly increased in all compartments (p < 0.05). Release of MMP 9 was not altered. Laser energy below the threshold of RPE cell death did not alter the release of MMP 2 or 9. The findings suggest that the release of active MMP 2 on the basal side of the RPE during wound healing following SRT may address age-related pathological changes of Bruch's membrane with a potential to slow degenerative macular ageing processes before irreversible functional loss has occurred.

Selective retina therapy for acute central serous chorioretinopathy.

AIMS: To evaluate selective retina therapy (SRT) as a treatment of acute central serous chorioretinopathy. METHODS: 30 eyes of 30 patients with central serous chorioretinopathy of at least a 3 months' duration were recruited. 14 eyes were randomised to an SRT group (Q-switched neodymium-doped yttrium lithium fluoride (Nd:YLF) laser, wavelength 527 nm, t=1.7 µs, energy 100-370 µJ, spot diameter 200 µm, pulse repetition rate 100 Hz,) and 16 eyes to a control group. After 3 months of follow-up, patients in the control group with persistence of subretinal fluid (SRF) were allocated to a cross-over group, treated with SRT and followed up for further 3 months. The main outcome measures were change of best-corrected Early Treatment Diabetic Retinopathy Study visual acuity (BCVA) and SRF. RESULTS: At 3 months of follow-up, the mean (SD) improvement of BCVA was significantly greater after SRT than in the control group: 12.7 (7.2) versus 6.3 (8.9) letters (p=0.04). SRF had decreased significantly more after SRT as compared with that the control group: 203 (136) µm versus 41 (150) µm (p=0.005). In eight eyes allocated to the cross-over group, the mean BCVA had increased during 3 months of follow up before SRT by 1.4 (5.2) letters and continued to increase during 3 months following SRT by 7.4 (6.3) letters, while SRF increased by 39.5 (160.2) µm before SRT and decreased by 151.5 (204.9) µm after SRT. In six of the eight eyes, SRF had completely resolved 3 months after SRT. CONCLUSIONS: SRT appears to expedite functional recovery and the re-absorption of SRF as compared with that in untreated controls. A larger prospective, randomised phase 3 confirmative patient study is warranted. TRIAL REGISTRATION NUMBER: NCT00987077.

Subretinal coapplication of recombinant tissue plasminogen activator and bevacizumab for neovascular age-related macular degeneration with submacular haemorrhage.

AIM: To evaluate the efficacy and safety of pars plana vitrectomy (ppV) with subretinal coapplication of recombinant tissue plasminogen activator (rtPA) and bevacizumab, and fluid-gas exchange for neovascular age-related macular degeneration (AMD) with submacular haemorrhage (SMH). METHODS: Consecutive interventional case series of 12 patients with neovascular AMD with SMH with a maximum history of 14 days. All patients underwent ppV with subretinal coapplication of rtPA and bevacizumab, and fluid-gas (20% SF6) exchange. Phakic patients underwent concomitant cataract surgery. Additional injections of bevacizumab were applied intravitreally 4 and 8 weeks postop. RESULTS: Complete displacement of SMH from the fovea was achieved in 9 of 12 patients. The mean best-corrected visual acuity (BCVA) improved significantly from preop logMAR 1.9 (range 3.0 to 0.7) to logMAR 1.2 (range 3.0 to 0.3) at 4 weeks postop (p = 0.01) and to logMAR 0.9 (range 1.6 to 0.2) at 12 weeks postop (p = 0.006). The mean improvement of BCVA 4 weeks postop as compared with preop was logMAR 0.7 (range -0.2 to 2.3). The mean improvement of BCVA 12 weeks postop as compared with preop was logMAR 0.96 (range -0.3 to 2.8). Overall, at 12 weeks postop, BCVA had improved in 10 patients, remained unchanged in one patient and worsened in one patient. CONCLUSION: PpV with subretinal coapplication of rtPA and bevacizumab, and fluid-gas exchange effectively displaces SMH and improves visual acuity in most patients.

[Retrospective case analysis of ophthalmological and systemic risk factors in patients with retinal vascular occlusion]. / Retrospektive Fallanalyse zum ophthalmologischen und internistischen Risikoprofil von retinalen Gefässverschlüssen.

OBJECTIVE: The aim was to determine systemic risk factors for acute central retinal artery occlusion (CRAO) and central retinal vein occlusion (CRVO) and to evaluate the usefulness of systemic diagnostics in CRAO and CRVO. METHODS: The study consisted of a retrospective chart review including 80 patients (CRAO 38, CRVO 42). All patients underwent systemic diagnostics including blood pressure measurement, blood cholesterol level, carotid Doppler imaging, transthoracic echocardiography (TTE), intraocular pressure measurement, glaucoma history and presence of thrombophilic factors. A systemic medical history was obtained. RESULTS: Systemic hypertension was found in 76.3% CRAO and 75.6% CRVO patients. Abnormal cardiac findings were detected in 61% (CRAO) and 22% (CRVO). Abnormal carotid findings were detected in 44.1% for CRAO and 9.5% for CRVO. Pathological thrombophilic factors were found in both groups for approximately 15%. CONCLUSIONS: TTE and carotid Doppler are important tools in the diagnosis of sources of emboli in patients with CRAO, while for CRVO abnormal findings are revealed by TTE and carotid Doppler less often. Thrombophilia should be ruled out in the absence of common risk factors, especially in younger patients and systemic hypertension should be adequately controlled.

[Expression of matrix metalloproteinase-19 in the human cornea. Wound healing in the MMP-19 knock-out mouse model]. / Expression von Matrixmetalloproteinase-19 in der humanen Kornea. Untersuchungen zur kornealen Wundheilung im MMP-19-knock-out-Mausmodell.

BACKGROUND: At present there are no data in the literature on the expression of matrix metalloprotein-19 in the human cornea. The aim of this study was to analyze the expression of matrix metalloproteinase-19 in the human cornea and to investigate its potential role in corneal wound healing using a MMP-19 knock-out mouse model. METHODS: A method with Western blotting and immunohistological staining for MMP-19 was performed using paraffin embedded human corneas. Excimer laser keratectomy was performed in wild type (wt) and MMP-19 knock-out (ko) mice and the rate of re-epithelialization was analyzed after 8 h and 18 h. RESULTS: MMP-19 was strongly expressed in the human corneal epithelium mainly in the basal cell layer. MMP-19 was not expressed in the corneal stroma. In the mouse model the size of the corneal lesion after 8 h was 83% (wt) and 89.9% (ko) of the initial area (p=0.09). After 18 h the lesion was 17% (wt) and 13.3% (ko) of the initial area (p=0.01). Laminin-5 was expressed in the migrating epithelial cells with no differences between wild type and knock-out mouse. CONCLUSION: MMP-19 showed a strong expression in the basal cells of the human corneal epithelium. Corneal re-epithelialization was slightly faster in the MMP-19 knock-out mouse. No differences in the expression of laminin-5 could be detected.

[Solar retinopathy: follow-up examinations with optical coherence tomography (OCT) and microperimetry]. / Retinopathia solaris: Verlaufsbeobachtung mit optischer Kohärenztomografie (OCT) und Mikroperimetrie.

BACKGROUND: Solar retinopathy is a phototoxic damage to the central retina. It may cause visual deterioration and a central scotoma with reading difficulties, that usually fade with time. Morphological and functional changes can be very subtle and are often inadequately detected by standard examinations. PATIENTS AND METHODS: The more affected, left eye of a 41-year-old female patient was examined clinically, by optical coherence tomography (OCT 3) and by MP 1-microperimetry during a 6-month follow up after gazing at a partial eclipse. RESULTS: At all times visual acuity was reduced to 0.7 causing visual deterioration. OCT examinations showed a subfoveal damage of decreasing extent, which was still detectable after 6 months. The retinal affection resulted in a persistent microscotoma of decreasing depth. CONCLUSION: OCT 3 and MP 1-microperimetry are able to detect the morphological and the functional damages in solar retinopathy at a level of sensitivity good enough to produce correlating results which allow the detection of subtle changes during follow-up.

[Autologous RPE-choroid translocation in exudative AMD. A case series of 10 consecutive patients]. / Autologe RPE-Chorioidea-Translokation bei exsudativer AMD. Eine Falldemonstration 10 konsekutiver Patienten.

BACKGROUND: To evaluate the retinal sensitivity and fixation pattern after removal of choroidal neovascularisation (CNV) and autologous retinal pigment epithelium (RPE)-choroid translocation in patients with exudative age-related macular degeneration (AMD). METHODS: The functional and morphologic results of 10 consecutive patients (nine with exudative AMD, one with geographic atrophy) were analysed. The mean follow-up was 16.8 (14-20) months. Functional evaluation was performed with the MP1 microperimeter. RESULTS: Preoperative visual acuity ranged from hand motion to 0.2 (decimal), and postoperative visual acuity ranged from hand motion to 0.4. Fixation on the graft was shown in four patients. Microperimetry proved light increment sensitivity over the graft in five patients. Light increment sensitivity could be kept on a constant level in four of these patients. Postoperative complications included retinal detachment (three), proliferative vitreoretinopathy (one), and development of CNV (one). CONCLUSION: Autologous RPE-choroid sheet translocation is feasible and comparatively safe. Fixation and light perception on the graft proved to be possible. Light increment sensitivity can be kept on a constant level for at least 20 months.