Macular Degeneration: Gelisken F

Ziemssen F, Gelisken F. · Department für Augenheilkunde, Eberhard-Karls-Universität Tübingen. · Klin Monatsbl Augenheilkd. · Pubmed #19173161 No free full text.

Abstract: Since anti-VEGF treatment has been proven to achieve a significant improvement of visual acuity in a cohort of patients with neovascular age-related macular degeneration (AMD), macular surgery and particularly the macular translocation with 360 degrees retinotomy (FMT: full macular translocation) have lost their former popularity. However, the approach of macular surgery still remains a promising therapy in selected cases. A prospective randomised study, comparing FMT and photodynamic therapy in subfoveal classic choroidal neovascularisation (CNV), recently showed the superiority of FMT in terms of visual gain. In spite of the postoperative complications and the disturbed binocular vision, the reading acuity and the life quality of many patients improved. Therefore, it is justified to discuss the chances and advantages of the FMT at least in selected cases. After all, case selection was an important determinant also in the phase III studies of ranibizumab; many patients seen during the routine consulting hours were excluded as a consequence of the study criteria. Most of them were suspected to achieve a less favourable outcome of the anti-VEGF regimen. Thus, patients who did not meet the inclusion criteria of recent studies or showed no response to the anti-VEGF therapy, as well as patients with extensive submacular bleeding or ruptures of the pigment epithelium can also be considered as candidates of FMT. Generally, in the presence of highly effective anti-VEGF drugs, FMT can be discussed for second-line treatment, if the fellow eye has poor function and no additional risk factors of the affected eye are known (e. g., hyperopia, large lesion size, etc). Detailed information relating to the potential adverse events have to be mentioned. Although the indication is restricted, surgeons should have the continuing ability to perform the challenging surgical procedure.

Jaissle GB, Ziemssen F, Petermeier K, Szurman P, Ladewig M, Gelisken F, Völker M, Holz FG, Bartz-Schmidt KU. · Abt. I, Universitätsaugenklinik Tübingen, Schleichstrasse 12, 72076 Tübingen. · Ophthalmologe. · Pubmed #16763863 No free full text.

Abstract: Application of VEGF inhibitors represents a treatment option for macular edema secondary to retinal vein occlusion that targets the disease at the causal molecular level. First reports on intravitreal injections of bevacizumab show promising morphological and functional effects and demonstrate that bevacizumab is a potent antiedematous agent in this context. A significant reduction of the central retinal thickness followed by a rapid improvement of visual acuity may be achieved within days. In a pilot study with a review period of 3 months, we found a significant improvement of one or more lines in 93% and four or more lines in 27% of eyes. This was associated with a concomitant significant reduction in central retinal thickness, which, however, was not sustained by a single injection (64% reduction after 1 month and 28% after 3 months). No relevant adverse events were noted. The duration of action after intravitreal bevacizumab administration is currently unknown. Reinjections will be necessary to maintain a lasting beneficial effect. Prospective, controlled long-term studies are mandatory to develop standardized treatment protocols that allow a safe and effective application of this off-label therapy.

Jaissle GB, Leitritz M, Gelisken F, Ziemssen F, Bartz-Schmidt KU, Szurman P. · University Eye Clinic, Centre for Ophthalmology, Eberhard-Karls University of Tuebingen, Schleichstr. 12, 72076 Tuebingen, Germany. · Graefes Arch Clin Exp Ophthalmol. · Pubmed #18696094 No free full text.

Abstract: BACKGROUND: To investigate the long-term effectiveness of intravitreal bevacizumab treatment in eyes with perfused macular edema due to branch retinal vein occlusion (BRVO). METHODS: In this prospective interventional case series, 23 consecutive, previously untreated eyes with perfused macular edema were treated with intravitreal bevacizumab (1.25 mg) injections and followed for 1 year. The main outcome measures were visual acuity (VA) and central retinal thickness (CRT). In addition, VA data were adapted to the non-logarithmic VA charts used in the previously published grid laser photocoagulation BRVO Study. RESULTS: The median VA gained 3.0 lines from baseline at 48 weeks. This was accompanied by a significant decrease of 39% of the median CRT. The mean number of re-injections was 1.6 during the first 6 months of follow-up and only 0.8 during the subsequent 6 months. In 65% of the cases, adapted VA data showed a gain of 1 or more lines and no eye lost more than 1 line. CONCLUSIONS: Repetitive intravitreal bevacizumab injections result in a significant long-term improvement of VA and CRT. The number of re-injections necessary to maintain this effect declined over time. However, the treatment seems to be only slightly better than grid laser photocoagulation.

Lüke M, Ziemssen F, Völker M, Altpeter E, Beutel J, Besch D, Bartz-Schmidt KU, Gelisken F. · University Eye Hospital, University of Lübeck, Lübeck, Germany. · Graefes Arch Clin Exp Ophthalmol. · Pubmed #19214552 No free full text.

Abstract: BACKGROUND: To report the outcome of best-corrected visual acuity (BCVA), near visual acuity (NVA), contrast sensitivity (CS) and vision-related quality of life (VRQOL) in patients 2 years after undergoing photodynamic therapy (PDT) or full macular translocation (FMT) for the treatment of neovascular age-related macular degeneration (AMD). METHODS: Fifty patients with predominantly classic subfoveal choroidal neovascularisation (CNV) secondary to AMD were randomized to PDT or FMT. BCVA was determined according a standardized protocol with ETDRS charts. NVA were calculated after testing with SNAB (Swiss National Association of and for the Blind) visual acuity cards. CS was measured with Pelli-Robson charts. The 39-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25 plus supplement) was performed. Primary end points were the changes of BCVA, NVA, CS and VRQOL at 24-month examination. RESULTS: A stabilisation of BCVA (+0.3 letters) was found in the FMT group, whereas a decrease of more than 12 letters (-12.6 letters) was found in the PDT group (p = 0.052). Mean NVA improved by 7.0 letters in the FMT group and was superior to the PDT group (-9.6 letters, p = 0.036), while mean CS showed a time-dependent decrease in both treatment groups (FMT: -3.3 letters, PDT: -3.8 letters, p = 0.726). Considering the results of the VRQOL scores, the improvement of the subscales scores for general vision (p = 0.015), mental health (p = 0.028) and near activity (p = 0.020) were significantly higher in the FMT group. CONCLUSIONS: FMT can stabilise BCVA and improve NVA over a period of 2 years in patients with subfoveal classic CNV secondary to neovascular AMD, whereas a decrease of BCVA and NVA was found in the PDT group. CS did not differ between FMT and PDT. A significant increase of VRQOL scores was only found in the FMT group and not in the PDT group. FMT seems to be a therapeutic approach that can increase visual function resulting in an improvement of patient's VRQOL, but exhibits a higher number of severe complications compared to PDT.

Pauleikhoff D, Scheider A, Wiedmann P, Gelisken F, Scholl HP, Roider I, Mohr A, Zlateva G, Xu X. · Augenabteilung am St. Franziskus-Hospital, Münster, Deutschland. · Ophthalmologe. · Pubmed #18709375 No free full text.

Abstract: BACKGROUND: Approximately 35,000 cases of neovascular age-related macular degeneration (AMD) occur annually in Germany. The neovascular form of AMD (NV-AMD) is responsible for severe vision loss associated with the disease in 90% of the cases. This study was conducted to assess the humanistic and economic burden of NV-AMD in the German population. METHODS: A cross-sectional, observational study of subject self-reported functional health, well-being, and disease burden among elderly subjects with (n=83) and without (n=93) NV-AMD in Germany was conducted. Patients participated in telephone surveys involving the National Eye Institute Visual Function Questionnaire (NEI-VFQ-25), the EuroQol (EQ-5D), the Hospital Anxiety and Depression Scale (HADS), and also reported history of falls, fractures, and healthcare resource utilization. Furthermore, the healthcare utilization and unit costs for the NV-AMD patients were calculated. RESULTS: The mean age of NV-AMD patients was 77.2 years and 64% were female. NV-AMD patients reported significantly worse vision-related function and overall well-being than controls (adjusted mean scores: NEI-VFQ-25 overall scale: 51.3 vs 96.3; p<0.0001) and significantly more depression symptoms than controls (HADS depression: 6.2 vs. 2.7; p<0.0001). NV-AMD patients also reported that the need for assistance with daily activities was more than 10 times greater compared to controls (26.5% vs. 2.2%; p<0.0001) and the prevalence of falls was 3 times that of the control group (13.3% vs 4.3%; p=0.031). Annual NV-AMD costs per patient were <euro> 9871, 6 times that of elderly patients without NV-AMD (<euro> 1559). Of the NV-AMD costs one-half were direct non-medical-related costs (assistance of ADL or social benefit) and one-third were direct medical costs. CONCLUSIONS: NV-AMD is associated with decreased functional abilities and quality of life, which result in an increase in healthcare resource utilization. Consequently, costs were higher for NV-AMD patients compared to controls. These findings emphasize the need for new NV-AMD treatments that will prevent vision loss and progression to blindness, and lessen the ensuing economic burden. Sponsored by Pfizer Inc. New York, US.

Leitritz M, Gelisken F, Inhoffen W, Voelker M, Ziemssen F. · Department of Ophthalmology, University Eye Hospital, Tuebingen, Germany. · Eye. · Pubmed #18535608 No free full text.

Abstract: BACKGROUND: Retinal pigment epithelium (RPE) tears after bevacizumab treatment for neovascular age-related macular degeneration accompanied by a pigment epithelial detachment (PED) might be caused by stretching forces on the already weakened RPE. The purpose of this study was to evaluate whether simple measurements of optical coherence tomography (OCT) can predict the individual risk of an RPE tear in preoperative candidates. METHODS: A retrospective chart review study of 393 consecutive patients with neovascular age-related macular degeneration evaluated OCT images (Stratus-OCT Zeiss, Jena, Germany). The height of the PED, the central retinal thickness, and the maximum retinal thickness were determined by two independent observers and retrospectively analysed. RESULTS: Fifteen patients with an RPE tear had a significant higher PED than the remaining study population. In contrast, no correlation was seen with the central retinal thickness. In a linear regression model, the probability of an RPE tear exponentially increased in dependence of the extent of PED. CONCLUSION: The risk of an RPE tear can be estimated by simple measurement of the height of the PED on OCT.

Gelisken F, Ziemssen F, Voelker M, Bartz-Schmidt KU, Inhoffen W. · Center for Ophthalmology, University of Tuebingen, Tuebingen, BW, Germany. · Eye. · Pubmed #18239678 No free full text.

Abstract: PURPOSE: To analyse retinal pigment epithelial (RPE) tears following single administration of intravitreal bevacizumab for neovascular age-related macular degeneration (AMD) during early follow-up. METHODS: Interventional, retrospective, non-comparative case series included 397 patients (409 eyes) of the 746 consecutive patients that met the eligibility criteria. Standardized visual acuity testing, fluorescein angiography, and optical coherence tomography were performed. Data collected included status of the fellow eye, previous treatment, subtypes of choroidal neovascularization (CNV), size and composition of the lesion. Multiple linear regression modelling was used to explore the effect of baseline parameters on the RPE tears. Primary end point was occurrence of RPE tears within 6 weeks after therapy. RESULTS: Fifteen of the 409 eyes (3.6%) developed RPE tear (95% confidence interval: 2.2-6.0, odds ratio: 26.3). The statistical modelling showed significant association between RPE tear and occult without classic CNV/predominantly haemorrhage vspredominantly/minimal classic CNV (P=0.019), as well as medium or large (>4 disc area) vssmall size of the total lesion (P=0.038). Previous treatment and status of the fellow eye did not statistically influence the risk of RPE tears. CONCLUSIONS: An RPE tear can develop in up to 3.6% of eyes with neovascular AMD following single administration of intravitreal bevacizumab in a short-term follow-up. Medium and large lesion size and occult without classic and predominantly haemorrhagic subtype of CNV were important predictive factors. Preoperative assessment of the lesion characteristics may help in identifying the risk of individual patients with neovascular AMD before intravitreal bevacizumab treatment.

Ziemssen F, Lüke M, Bartz-Schmidt KU, Gelisken F. · Department for Ophthalmology, University Eye Hospital, Eberhard-Karls University, Schleichstr. 12-16, 72076 Tuebingen, Germany. · Graefes Arch Clin Exp Ophthalmol. · Pubmed #18071731 No free full text.

Abstract: PURPOSE: To report the change of contrast sensitivity (CS) after photodynamic therapy (PDT) vs full macular translocation (FMT) for neovascular age-related macular degeneration (AMD), and to relate this to other measures of visual function (distance and near acuity). METHODS: Fifty patients (50 eyes) with predominantly classic subfoveal choroidal neovascularisation (CNV) secondary to AMD were randomized to PDT or FMT. CS was measured with Pelli-Robson charts. Acuity scores of near visual function (NVS) were calculated after testing with visual acuity cards of the Swiss National Association of and for the Blind (SNAB). Best corrected distance visual acuity (DVA) was determined according to a standardized protocol with EDTRS charts. Primary end point was the change of CS at 12-month examination from baseline. The interaction of the CS with NVS and DVA was analysed. RESULTS: Mean CS showed a decrease in both treatment groups (FMT: -2 letters, PDT: -3 letters, p=0.969) at 12-month examination from baseline. While mean NVS improved by seven letters in the FMT group, a decrease of more than ten letters was seen in the PDT group (p<0.05). We found no agreement between CS and high-contrast acuity (NVS, DVA). In FMT patients, the parameters at baseline (CS, NVS, DVA) correlated poorly with the corresponding 12-month results, therefore providing no informative basis to predict the later functional development. In contrast, PDT patients showed strong baseline-to-outcome coherence with baseline measures also associated with better final values. CONCLUSIONS: Although FMT can initiate recovery of near and distance acuity over the period of 1 year in selected patients with classic CNV, CS did not differ between FMT and PDT. We found no close connection of CS with DVA or NVS, especially after FMT. Knowledge about the unequal variation of visual parameters can provide more comprehensive information when advising patients on different therapeutic options. That also applies in particular to vascular endothelial growth factor inhibitors, which seem to promise an even higher extent of gain in CS and to reach the peak of recovery at an earlier time.

Nguyen NX, Besch D, Bartz-Schmidt K, Gelisken F, Trauzettel-Klosinski S. · Department of Ophthalmology II, University Eye Hospital, Tübingen, Germany. · Acta Ophthalmol Scand. · Pubmed #17651462 No free full text.

Abstract: PURPOSE: The aim of the present study was to evaluate the power of magnification required, reading performance with low-vision aids and vision-related quality of life with reference to reading ability and ability to carry out day-to-day activities in patients after macular translocation. METHODS: This study included 15 patients who had undergone macular translocation with 360-degree peripheral retinectomy. The mean length of follow-up was 19.2 +/- 10.8 months (median 11 months). At the final examination, the impact of visual impairment on reading ability and quality of life was assessed according to a modified 9-item questionnaire in conjunction with a comprehensive clinical examination, which included assessment of best corrected visual acuity (BCVA), the magnification power required for reading, use of low-vision aids and reading speed. Patients rated the extent to which low vision restricted their ability to read and participate in other activities that affect quality of life. Responses were scored on a scale of 1.0 (optimum self-evaluation) to 5.0 (very poor). RESULTS: In the operated eye, overall mean postoperative BCVA (distance) was not significantly better than mean preoperative BCVA (0.11 +/- 0.06 and 0.15 +/- 0.08, respectively; p = 0.53). However, 53% of patients reported a subjective increase in visual function after treatment. At the final visit, the mean magnification required was x 7.7 +/- 6.7. A total of 60% of patients needed optical magnifiers for reading and in 40% of patients closed-circuit TV systems were necessary. All patients were able to read newspaper print using adapted low-vision aids at a mean reading speed of 71 +/- 40 words per minute. Mean self-reported scores were 3.2 +/- 1.1 for reading, 2.5 +/- 0.7 for day-to-day activities and 2.7 +/- 3.0 for outdoor walking and using steps or stairs. Patients' levels of dependency were significantly correlated with scores for reading (p = 0.01), day-to-day activities (p < 0.001) and outdoor walking and using steps (p = 0.001). CONCLUSIONS: The evaluation of self-reported visual function and vision-related quality of life in patients after macular translocation is necessary to obtain detailed information on treatment effects. Our results indicated improvement in patients' subjective evaluations of visual function, without significant improvement in visual acuity. The postoperative clinical benefits of treatment coincide with subjective benefits in terms of reading ability, quality of life and patient satisfaction. Our study confirms the importance and efficiency of visual rehabilitation with aids for low vision after surgery.

Suesskind D, Voelker M, Bartz-Schmidt KU, Gelisken F. · Center for Ophthalmology, University of Tuebingen, Tuebingen, Germany. · Eye. · Pubmed #17401325 No free full text.

Abstract: PURPOSE: To report the long-term functional and anatomical outcome of full macular translocation (FMT) in eyes with neovascular age-related macular degeneration (AMD) following photodynamic therapy (PDT). METHODS: Twelve eyes of 12 consecutive patients with neovascular AMD who were PDT-nonresponders and underwent FMT were analysed. Best-corrected visual acuity (BCVA) measurement, fundus photography, and fluorescein angiography at baseline and at follow-up examinations in 3 months intervals were performed. Primary end point was change of BCVA from baseline to last visit. RESULTS: Totally 12 eyes of 12 patients were analysed. Mean time interval between the last PDT and FMT was 3.7 months (range 1-10 months). Mean follow-up after FMT was 25.6 months. BCVA ranged at baseline from 20/1000 to 20/80 (mean 20/230). At the last visit, mean BCVA was by 20/185. BCVA improved in 50% (6/12) of eyes by more than 1 line. Twenty five per cent (3/12) of eyes had final BCVA within +/-1 line from baseline. In 25% (3/12) of eyes the BCVA decreased by more than 1 line. One eye had recurrent CNV. In four eyes a cystoid macular oedema developed. No retinal detachment or disturbing diplopia was noted. CONCLUSIONS: In the present study, FMT in PDT-nonresponders stabilised or improved visual acuity in the majority of the eyes in a mean follow-up period of nearly 2 years. FMT can be considered as a therapeutical option in eyes who are nonresponders to the PDT in neovascular AMD.

Lüke M, Januschowski K, Warga M, Beutel J, Leitritz M, Gelisken F, Grisanti S, Schneider T, Lüke C, Bartz-Schmidt KU, Szurman P, Anonymous00138. · Department of Ophthalmology, University of Tuebingen, Schleichstr. 12-16, D-72076 Tuebingen, Germany. · Br J Ophthalmol. · Pubmed #17383998 No free full text.

Abstract: AIM: To investigate the retinal toxicity of bevacizumab in co-application with a commercially available recombinant tissue plasminogen activator (rt-PA), and to facilitate a new therapeutic concept in the treatment of massive subretinal haemorrhage caused by neovascular age-related macular degeneration (AMD). METHODS: Isolated bovine retinas were perfused with an oxygen-preincubated nutrient solution. The electroretinogram (ERG) was recorded as a transretinal potential using Ag/AgCl electrodes. Bevacizumab (0.25 mg/ml) and rt-PA (20 microg/ml) were added to the nutrient solution for 45 min. Thereafter, the retina was reperfused for 60 min with normal nutrient solution. Similarly, the effects of rt-PA (20 microg/ml, 60 microg/ml and 200 mug/ml) on the a- and b-wave amplitudes were investigated. The percentages of a- and b-wave reduction during application and at washout were calculated. RESULTS: During application of bevacizumab (0.25 mg/ml) in co-application with 20 microg/ml (rt-PA), the ERG amplitudes remained stable. The concentrations of rt-PA alone (20 microg/ml and 60 microg/ml) did not induce significant reduction of the b-wave amplitude. In addition, 20 microg/ml rt-PA did not alter the a-wave amplitude. However, 60 microg/ml rt-PA caused a slight but significant reduction of the a-wave amplitude. A full recovery was detected for both concentrations during the washout. At the highest tested concentration of 200 microg/ml rt-PA, a significant reduction of the a- and b-wave amplitudes was provoked during the exposure. The reduction of ERG amplitudes remained irreversible during the washout. CONCLUSION: The present study suggests that a subretinal injection of 20 microg/ml rt-PA in co-application with bevacizumab (0.25 mg/ml) for the treatment of massive subretinal haemorrhage seems possible. This is a safety study. Therefore, we did not test the clinical effectiveness of this combined treatment.

Lüke M, Ziemssen F, Bartz-Schmidt KU, Gelisken F. · University Eye Hospital, Centre for Ophthalmology, Eberhard-Karls University of Tuebingen, Schleichstr. 12-16, 72076 Tuebingen, Germany. · Graefes Arch Clin Exp Ophthalmol. · Pubmed #17347809 No free full text.

Abstract: PURPOSE: To assess visual function and its effects on vision-targeted, health-related quality of life (QOL) of patients with neovascular age-related macular degeneration (AMD) treated with photodynamic therapy (PDT) or full macular translocation (FMT). METHODS: Fifty patients with predominantly classic subfoveal choroidal neovascularisation (CNV) secondary to AMD were randomised to PDT or FMT. To test the vision-targeted QOL, the 39-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25 plus supplement) was administered prior to and 1 year after therapy. The change of vision-related QOL at 1 year in comparison to baseline was defined as primary end point. RESULTS: The vision-related subscales showed a stabilisation or even higher mean scores at 1 year in both treatment groups. A significant improvement in the quality of the subject's vision-related subscales was only observed after FMT correlating with a more frequent increase in visual acuity. Comparing the results of the QOL scores after 1 year, the improvement of the subscale scores general vision (p = 0.03), mental health (p = 0.02) and dependency (p = 0.03) were significantly higher in the FMT arm. CONCLUSIONS: FMT and PDT can achieve a stabilisation in vision-related QOL, in which FMT was superior to the PDT after 1 year. The discrepancy between the amount of patients with an increased visual acuity after FMT and a moderate improvement in QOL might be caused by the onset of complications related to this surgical procedure. Besides visual acuity, the impact of therapy-related complications has to be taken into consideration when evaluating new therapeutic concepts in exudative AMD.

Aisenbrey S, Gelisken F, Szurman P, Bartz-Schmidt KU. · Center of Ophthalmology, University of Tuebingen, Schleichstr. 12, D-72076 Tuebingen, Germany. · Br J Ophthalmol. · Pubmed #17301123 No free full text.

Abstract: OBJECTIVE: To report the functional and morphological outcome of surgical treatment of peripapillary choroidal neovascularisation due to age-related macular degeneration. METHODS: Consecutive interventional case series of eight patients with extensive peripapillary choroidal neovascularisation and accompanying haemorrhage who underwent subretinal surgery including extraction of the neovascular complex. Ophthalmic examination, including visual acuity testing, colour photography and fluorescein angiography, was performed at baseline and at 3, 6, 9 and 12 months, and then yearly. RESULTS: Mean follow-up was 26 months (12-60 months). Preoperative best corrected visual acuity (BCVA) ranged from logMAR (logarithm of minimum angle of acuity) 1.0 (20/200) to logMAR 0.0 (20/20), with a mean of logMAR 0.5 (20/63). Mean postoperative BCVA was logMAR 0.3 (20/40). BCVA improved in six patients, was stable in one patient and deteriorated in one patient. Two years after surgery, one patient developed recurrence of the CNV that was removed surgically. One patient showed retinal detachment 5 years after subretinal surgery. CONCLUSIONS: In this small case series of PPCNV, functional improvement was achieved after surgery in the majority of patients. Surgical extraction of the CNV represents an alternative treatment option in eyes with vision-threatening extensive PPCNV. Randomised controlled studies seem to be justified to evaluate further the beneficial effect and long-term functional outcome of this therapy approach.

Gelisken F, Voelker M, Schwabe R, Besch D, Aisenbrey S, Szurman P, Grisanti S, Herzau V, Bartz-Schmidt KU. · Centre for Ophthalmology, University of Tuebingen, Schleichstr. 12, 72076 Tuebingen, Germany. · Graefes Arch Clin Exp Ophthalmol. · Pubmed #17219106 No free full text.

Abstract: BACKGROUND: The purpose of this study was to compare full macular translocation (FMT) with photodynamic therapy (PDT) in the treatment of neovascular age-related macular degeneration (AMD). METHODS: In a prospective, randomised, non-masked, mono-center, pilot-trial, 50 eyes of 50 patients were assigned to either FMT or PDT. Baseline and control examinations in 3-monthly intervals over a 12-month period included standardized protocol refraction, visual acuity testing and fluorescein angiography. Primary outcome measurements were made to establish the change in distant visual acuity from the baseline to the 12-month examination. The statistical analyses were carried out on the intent-to-treat principle. RESULTS: The improvement of one or more ETDRS lines was 56% (14/25) of the eyes in the FMT and 16% (4/25) of the eyes in the PDT arm (P = 0.007). Twenty eyes (80%) in the FMT and 16 eyes (64%) in the PDT group had less than three ETDRS lines of vision loss (P = 0.35). Retinal detachment (six eyes) and diplopia (five patients) were recorded in the FMT group. None of the eyes treated in the FMT group had phtysis. CONCLUSION: This pilot study showed that no statistically significant difference existed between the FMT and PDT in terms of the vision loss of less than three ETDRS lines in eyes with neovascular AMD. The chance of vision improvement was significantly higher for the patients in the FMT group. However, in the era of promising therapy with anti-vascular endothelial growth factor for neovascular AMD, FMT should not be offered as a standard primary procedure for neovascular AMD.

Aisenbrey S, Ziemssen F, Völker M, Gelisken F, Szurman P, Jaissle G, Grisanti S, Bartz-Schmidt KU. · Center of Ophthalmology, University of Tuebingen, Schleichstrasse 12, 72076 Tuebingen, Germany. · Graefes Arch Clin Exp Ophthalmol. · Pubmed #17186262 No free full text.

Abstract: BACKGROUND: The purpose of the study is to report data on short-term safety of intravitreal bevacizumab treatment and its effect on visual function, central retinal thickness, and angiographical changes of occult choroidal neovascularization due to age-related macular degeneration. METHODS: A consecutive interventional case series of 30 patients with active subfoveal occult choroidal neovascularization secondary to age-related macular degeneration was followed after one intravitreal injection of 1.25 mg bevacizumab at baseline and subsequent injections following standardized criteria. At baseline and follow-up visits patients had visual acuity assessment, intraocular pressure measurement, fluorescein angiography, and optical coherence tomography imaging. RESULTS: No serious ocular or systemic adverse events were identified. A significant increase of intraocular pressure or signs of retinal toxicity or endophthalmitis were not detected in any patient. Optical coherence tomography revealed significant decrease (p < 0.001) in central retinal thickness after 1 week, 4 weeks, and 12 weeks, respectively. Fluorescein leakage decreased within 1 week and improvement was maintained at week 12 in the majority of patients. Visual acuity improved or remained stable in 29 of 30 patients; improvement of 3 or more lines was seen in 14 of 30 patients; one patients showed improvement of 6 lines. No patient had severe vision loss of 6 lines or more; moderate vision loss of 3 lines was seen in one patient. Re-injections of bevacizumab according to standard criteria were performed one to two times during the follow-up period of 12 weeks with a re-injection interval of 4 to 18 weeks (median 8 weeks). CONCLUSIONS: Short-term results suggest that intravitreal injection of bevacizumab is well tolerated and for the majority of patients with occult choroidal neovascularization in AMD results in improvement of visual acuity, decrease in central retina thickness, and reduction of angiographic leakage of the lesion. Bevacizumab as intravitreal treatment may provide a novel therapeutic option for selected patients with exudative AMD. Randomized prospective multicenter trials seem justified to further evaluate long term effects and impact of intravitreal bevacizumab on different subtypes of AMD compared to established therapies.

Tatar O, Kaiserling E, Adam A, Gelisken F, Shinoda K, Völker M, Lafaut BA, Bartz-Schmidt KU, Grisanti S. · University Eye Clinic at the Centre for Ophthalmology, Eberhard-Karls-University, Tübingen, Germany. · Arch Ophthalmol. · Pubmed #16769835 links to  free full text

Abstract: OBJECTIVE: To examine the impact of photodynamic therapy (PDT) on angiogenesis in human choroidal neovascular membranes with respect to vascular endothelial growth factor (VEGF) expression, proliferation, and vascularization. METHODS: Retrospective review of an interventional case series of 50 patients (50 eyes) who underwent removal of choroidal neovascular membranes. Choroidal neovascularization was secondary to age-related macular degeneration. Twenty patients were treated with PDT 3 to 655 days before surgery. Choroidal neovascular membranes were stained for CD34, CD105, Ki-67, cytokeratin 18, and VEGF. Thirty choroidal neovascular membranes secondary to age-related macular degeneration without previous treatment were used as controls. RESULTS: Specimens without pretreatment disclosed varying degrees of vascularization, proliferative activity, and VEGF expression by different cells. Specimens treated with PDT 3 days earlier showed mostly occluded vessels, damaged endothelial cells, and low proliferative activity. In contrast, specimens excised at later time points after PDT were highly vascularized and proliferating. This chronology was associated with an impressive VEGF immunoreactivity unique to retinal pigment epithelial cells shortly after PDT that also shifted to other cells at later time points. CONCLUSIONS: Photodynamic therapy induces selective vascular damage in choroidal neovascular membranes. The effectiveness and selectivity of this treatment, however, seem to be jeopardized by a rebound effect initiated by enhanced VEGF expression in retinal pigment epithelial cells.

Petermeier K, Tatar O, Inhoffen W, Völker M, Lafaut BA, Henke-Fahle S, Gelisken F, Ziemssen F, Bopp S, Bartz-Schmidt KU, Grisanti S. · Univerisity Eye Clinic at the Centre for Ophthalmology, Eberhard-Karls University Tuebingen, Schleichstrasse 12-16, 72076 Tuebingen, Germany. · Br J Ophthalmol. · Pubmed #16613924 links to  free full text

Abstract: AIM: To evaluate the impact of verteporfin photodynamic therapy (PDT) on the induction of apoptosis in choroidal neovascular membranes (CNV) secondary to age related macular degeneration. METHODS: Retrospective review of 22 surgically excised CNV. 12 of these patients had been treated with PDT 3-146 days previously. Apoptotic cells were detected with the TUNEL technique and compared to the expression of CD34 (endothelial cells, EC), CD105 (activated endothelial cells), Ki-67 (proliferation marker), and cytokeratin18 (retinal pigment epithelial cells, RPE). RESULTS: CNV excised 3 days after PDT were characterised both by collapsed and patent vessels. The EC displayed a statistical significant positive TUNEL reaction when compared to the remaining treated CNV (p < 0.001) and untreated CNV (P = 0.002). The proliferative activity was reduced. CNV excised 1-5 months after PDT displayed a patent vascularisation and high proliferative activity. All membranes either treated or untreated disclosed only sporadic TUNEL positive cells within the stroma and the RPE. CONCLUSIONS: Verteporfin PDT leads to selective and effective damage of EC within CNV. Both patent and occluded vessels were lined by apoptotic EC. This finding and the increased expression of proliferation marker at later time points suggest that revascularisation after PDT is caused by angiogenesis rather than recanalisation.

Schneider U, Gelisken F, Inhoffen W, Bartz-Schmidt KU. · University Eye Clinic Tübingen, Tübingen, Germany. · Ophthalmologica. · Pubmed #16123558 No free full text.

Abstract: PURPOSE: To analyze and compare the angiographic features of retinal vascular anomalous complex (RVAC) in patients with a vascularized pigment epithelial detachment (PED) secondary to age-related macular degeneration. METHODS: Retrospective evaluation of fluorescein and indocyanine green angiographies of 180 patients with occult choroidal neovascularization and PED. RESULTS: On indocyanine green angiography (ICGA), RVAC demonstrated as a focal hyperfluorescence in connection with retinal choroidal anastomosis was identified in 12 of the 180 eyes (6.7%) with a vascularized PED. In comparison, fluorescein angiography revealed RVAC in 6 of the 12 eyes. Associated clinical and angiographic features were intraretinal hemorrhage in all 12 eyes, cystoid macular edema in 6 eyes and preretinal hemorrhage in 4 eyes. CONCLUSIONS: RVAC is better delineated on ICGA than on fluorescein angiography. In clinically suspected cases with a vascularized PED in connection with intraretinal hemorrhage and/or cystoid macular edema, ICGA should be performed to enhance management considerations.

Voelker M, Gelisken F, Ziemssen F, Wachtlin J, Grisanti S. · Department of Ophthalmology I, University of Tübingen, Germany. · Graefes Arch Clin Exp Ophthalmol. · Pubmed #16010552 No free full text.

Abstract: PURPOSE: To report the results of verteporfin photodynamic therapy (PDT) of extrafoveal predominantly classic choroidal neovascularisation (CNV) secondary to age-related macular degeneration (AMD). METHODS: In this retrospective study 20 consecutive patients (20 eyes) undergoing verteporfin PDT for extrafoveal predominantly classic CNV in AMD were examined. Colour photography of the fundus, fluorescein angiography and complete ophthalmic examination, including visual acuity assessment with ETDRS charts, were performed before treatment and at 3-month intervals thereafter. The primary outcome criterion was the change in visual acuity. The secondary outcome criterion was the extension of the CNV beneath the centre of the fovea during the follow-up period. RESULTS: Mean follow-up time of the patients was 24.2 months (range 12 to 58 months). Visual acuity at baseline varied from 20/200 to 20/20 (mean 20/50+/-2.3 lines). Final visual acuity ranged from 20/1000 to 20/20 (mean 20/200+/-5.1 lines) (P<0.001). In 85% (17/20) of the eyes visual acuity worsened. Visual acuity improved in 15% (3/20) of the eyes. During the course of the follow-up period, subfoveal extension of the CNV was detected in 80% (16/20) of the eyes. CONCLUSION: In 85% of the eyes with extrafoveal predominantly classic CNV secondary to AMD, visual acuity worsened after verteporfin PDT in an average follow-up time of 24 months. Subfoveal CNV was found in 80% of the eyes during follow-up. Even though verteporfin PDT can preserve visual acuity in selected cases, deterioration was seen in the majority of the patients.

Schneider U, Gelisken F, Inhoffen W. · University Eye Clinic Tübingen, Tübingen, Germany. · Acta Ophthalmol Scand. · Pubmed #15799723 No free full text.

Abstract: PURPOSE: To analyse the frequency of conversion from occult with no classic choroidal neovascularization (CNV) and occult with minimally classic CNV into predominantly classic CNV secondary to age-related macular degeneration. METHODS: Retrospective evaluation of baseline and repeat angiograms of 54 eyes with a follow-up of 6-12 months. RESULTS: In the group with initially occult with no classic CNV, nine of 40 eyes (23%) progressed to a predominantly classic lesion, whereas in the group of occult with a minimally classic CNV, 10 of 14 eyes (71%) eyes developed a predominantly classic CNV. CONCLUSIONS: The proportion of eyes that develop predominantly classic CNV is much higher in eyes with initially occult and minimally classic CNV, compared with eyes with initially occult and no classic CNV. Our data suggest that the natural course of CNV secondary to AMD begins as occult and progresses to classic CNV.

Gelisken F, Karim-Zoda K, Grisanti S, Bartz-Schmidt KU. · Universitaets-Augenklinik, Schleichstr. 12, 72076, Tuebingen, Germany. · Graefes Arch Clin Exp Ophthalmol. · Pubmed #15650855 No free full text.

Abstract: PURPOSE: To report a case of retinal pigment epithelial tear treated by macular translocation with 360 degrees retinotomy. METHODS: Interventional case report. A 75-year-old woman with neovascular age-related macular degeneration and retinal pigment epithelial tear underwent macular translocation with 360 degrees retinotomy and silicone oil tamponade. After 3 months, pars plana vitrectomy, silicone oil removal, and muscle surgery were performed. RESULTS: Twenty-two months after macular translocation surgery, the visual acuity of the patient had improved to 20/50 (preoperative 20/200). No proliferative vitreoretinopathy or recurrence of the choroidal neovascularisation was observed. CONCLUSIONS: Macular translocation surgery with 360 degrees retinotomy can improve vision in retinal pigment epithelial tear secondary to neovascular age-related macular degeneration.

Schlote T, Freudenthaler N, Gelisken F. · Augenklinik, Universitätsklinikum, Tübingen. · Ophthalmologe. · Pubmed #15526102 No free full text.

Abstract: BACKGROUND: Acute secondary angle closure glaucoma after massive vitreous and subretinal hemorrhage from exudative age related macular degeneration is a seldom, but devastating complication of an anticoagulative therapy. PATIENTS: Four patients (age range 70-76 years) developed unilateral acute angle closure glaucoma after massive intraocular bleeding due to exudative age-related macular degeneration and anticoagulative therapy. Three patients received Phenprocomoun and one patient thrombolytic therapy with heparin. One eye had led to blindness at initial investigation. Pars plana vitrectomy was performed in the remaining three eyes. Within a few months, 2 of these 3 eyes were blind, one eye had light perception and all three eyes developed hypotonia. CONCLUSION: Acute angle closure glaucoma after intraocular bleeding may be the initial clinical manifestation of overtreatment with anticoagulants. Early pars plana vitrectomy probably will increase the surveillance rate of the eye but not the visual prognosis.

Gelisken F, Inhoffen W, Karim-Zoda K, Grisanti S, Partsch M, Voelker M, Bartz-Schmidt KU. · Department of Ophthalmology I, University of Tuebingen, Germany. · Graefes Arch Clin Exp Ophthalmol. · Pubmed #15258778 No free full text.

Abstract: BACKGROUND: To identify the frequency of new subfoveal hemorrhage and its impact on visual acuity 2 weeks following verteporfin photodynamic therapy (PDT) in the treatment of predominantly classic subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). METHODS: Retrospective, noncomparative, consecutive, interventional case series. At a tertiary retinal referral center, 104 eyes of 97 consecutive patients with predominantly classic subfoveal CNV were treated by PDT. Morphological outcomes include new subfoveal hemorrhage assessed on the photo review (pretreatment, 2 and 12 weeks after PDT). Visual acuity outcomes include moderate (3-5 ETDRS lines) and severe (6 and more ETDRS lines) loss of visual acuity at 2 weeks after PDT. RESULTS: In this study, 104 eyes of 97 patients were analyzed. CNV in all eyes was secondary to AMD. New subfoveal hemorrhage was found in 22% (23/104) of the eyes 2 weeks following PDT. 17.4% (4/23) of the eyes with new subfoveal hemorrhage had moderate or severe loss of visual acuity. In such eyes the 12-week examination revealed considerable resorption of the new subfoveal hemorrhage with some improvement of visual acuity. CONCLUSIONS: In 3.8% of the eyes that underwent PDT for predominantly classic subfoveal CNV secondary to AMD, new subfoveal hemorrhage may result in moderate or severe loss of visual acuity within 2 weeks. In all eyes with new subfoveal hemorrhage, considerable resorption of the hemorrhage and some improvement of the visual acuity were seen at 12 weeks. Candidates for PDT should be informed about the low risk of this complication.

Grisanti S, Tatar O, Canbek S, Lafaut BA, Gelisken F, Inhoffen W, Szurman P, Aisenbrey S, Oficjalska-Mlynczak J, Bartz-Schmidt KU. · Department of Ophthalmology I, Division of Vitreoretinal Surgery, Eberhard-Karls University of Tuebingen, Schleichstrasse 12-15, 72076 Tuebingen, Germany. · Am J Ophthalmol. · Pubmed #15126158 No free full text.

Abstract: PURPOSE: To evaluate the vascularization and proliferative activity in choroidal neovascular membranes due to age-related macular degeneration after verteporfin photodynamic therapy and submacular removal. DESIGN: Interventional case series. METHODS: In a retrospective review of seven patients who underwent removal of subfoveal classic choroidal neovascular membranes after treatment with photodynamic therapy 3 to 146 days earlier, membranes were stained for CD 34, CD 105, and Ki-67 and correlated with clinical pictures and fluorescein angiography. RESULTS: Fluorescein angiography performed on the day of surgery disclosed nonperfusion of the treated area 3 days after photodynamic therapy, but perfusion and leakage were seen at greater post-photodynamic therapy intervals. Membranes excised 3 days after photodynamic therapy showed CD34 and CD105 positive, mostly occluded vessels. The endothelial cells appeared damaged. Ki-67 activity was low. In membranes excised 34 to 146 days after photodynamic therapy, all vessels appeared patent and were lined by healthy endothelial cells with strong expression of CD34 and CD105. Ki-67 expression was elevated after 34 days but decreased thereafter. CONCLUSION: Photodynamic therapy did not cause a general or complete occlusion of vessels within the choroidal neovascular membranes, as suggested by fluorescein angiography 3 days postintervention, but the endothelial cells appeared to be severely damaged. Proliferative activity within these specimens was reduced. At longer intervals after photodynamic therapy, the fibrovascular tissue seemed to recover; perfusion, hyperfluorescence, and leakage of the choroidal neovascular membranes could be detected by fluorescein angiography. The clinical appearance showed a correlation with the immunohistologic characteristics of an increased proliferative activity and patent vascularization.

Gelisken F, Lafaut BA, Inhoffen W, Voelker M, Grisanti S, Bartz-Schmidt KU. · Department of Ophthalmology I, University of Tuebingen, Schleichstrasse 12, 72076 Tuebingen, Germany. · Br J Ophthalmol. · Pubmed #14736776 links to  free full text

Abstract: AIMS: To report the clinicopathologic findings of surgically excised choroidal neovascularisation (CNV) three days after verteporfin photodynamic therapy (PDT). METHODS: In three patients (three eyes) with age related macular degeneration, the CNV was surgically removed three days after PDT. The CNV specimens were examined by light microscopy. RESULTS: The patients had subfoveal classic CNV. Fluorescein angiography revealed non-perfusion of the CNV after PDT and before surgery in all eyes. The light microscopy of the CNV membranes showed swollen and damaged endothelium. Thrombus formation or vascular occlusion in the CNV vessels was not detected. CONCLUSION: PDT did not cause a thrombosis of the vessels within the CNV three days after PDT. Severe endothelial damage of the CNV was observed and is likely a primary effect of PDT. Non-perfusion of the CNV at this stage is possibly secondary to occlusion at a deeper level, namely the underlying feeding choroid.