Faik Gelisken

Retinal pigment epithelial tear after photodynamic therapy for choroidal neovascularization

PURPOSE To report a case of retinal pigment epithelial tear after photodynamic therapy for choroidal neovascularization. METHODS Case report. A 74-year-old woman with exudative age-related macular degeneration and classic subfoveal choroidal neovascularization RE underwent photodynamic therapy with verteporfin. RESULTS Ophthalmoscopy and fluorescein angiography RE disclosed a retinal pigment epithelial tear in the area of photodynamic therapy. CONCLUSION This case presents the first report of a retinal pigment epithelial tear after photodynamic therapy with verteporfin for subfoveal choroidal neovascularization in age-related macular degeneration.

Effects of bevacizumab on retinal function in isolated vertebrate retina.

Background: Bevacizumab (Avastin) is a recombinant protein that targets vascular endothelial growth factor (VEGF). In vitro, bevacizumab inhibits VEGF induced cell proliferation and tissue factor production. Abnormal angiogenesis involving VEGF is a central event during the development of choroidal neovascularisation (CNV). The present study was designed to evaluate the short term toxic effects of bevacizumab on retinal function for a therapeutic intraocular application. Methods: Isolated bovine retinas were perfused with an oxygen pre-incubated nutrient solution. The electroretinogram (ERG) was recorded as a transretinal potential using silver/silver chloride electrodes. Bevacizumab was added in different concentrations to the nutrient solution for 45 minutes. Thereafter the retina was reperfused for 60 minutes with normal nutrient solution. The percentage of a-wave and b-wave reduction during the application of bevacizumab was calculated and compared to control recordings. Results: During the application of three different concentrations of bevacizumab (0.08 mg/ml, 0.25 mg/ml, 0.8 mg/ml) no significant reduction of the a-wave and b-wave amplitude was observed. During the washout, the ERG amplitudes were unchanged. Conclusion: The present study suggests that an intraocular application of 0.25 mg/ml bevacizumab for the treatment of CNV is reasonable. No significant short term effects of bevacizumab on retinal function were detected, but long term effects cannot be excluded.

The retinal tolerance to bevacizumab in co‐application with a recombinant tissue plasminogen activator

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 μg/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 μg/ml, 60 μg/ml and 200 μg/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 μg/ml (rt-PA), the ERG amplitudes remained stable. The concentrations of rt-PA alone (20 μg/ml and 60 μg/ml) did not induce significant reduction of the b-wave amplitude. In addition, 20 μg/ml rt-PA did not alter the a-wave amplitude. However, 60 μg/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 μg/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 µg/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.

Full macular translocation (FMT) versus photodynamic therapy (PDT) with verteporfin in the treatment of neovascular age-related macular degeneration: 2-year results of a prospective, controlled, randomised pilot trial (FMT-PDT)

BackgroundThe 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).MethodsIn a prospective, randomised, non-masked, monocenter, 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.ResultsThe 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.ConclusionThis 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.

Visualization and follow-up of acute macular neuroretinopathy with the Spectralis® HRA+OCT device

BackgroundAcute macular neuroretinopathy (AMNR) is a rare disease entity, the diagnosis of which is frequently complicated by the subtlety of biomicroscopic findings.MethodsTwo cases of AMNR are presented, in which the diagnosis and follow-up was enabled using the Spectralis® HRA+OCT in the absence of clear biomicroscopic findings.ResultsThe typical lesions were visualized by hyporeflexion during infrared imaging and faded over time. With spectral domain optical coherence tomography, changes in the outer retina in the affected regions were documented, with no change over time.ConclusionThe broader availability of this technology may enhance the diagnosis and follow-up of AMNR.

Clinicopathological findings of choroidal neovascularisation following verteporfin photodynamic therapy

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.

Verteporfin photodynamic therapy induced apoptosis in choroidal neovascular membranes

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.

Assessment of visual function in choroidal neovascularization with scanning laser microperimetry and simultaneous indocyanine green angiography.

Abstract• Background: Clinical management and treatment of diseases with choroidal neovascularization (CNV) are mainly based on visual acuity, which may give an incomplete picture of the associated visual dysfunctions. With the advent of new experimental treatment modalities such as alfa-interferon, radiation, or surgical excision of CNV, it is increasingly important to develop better methods for characterizing the associated visual function. Microperimetry with the scanning laser ophthalmoscope (SLO) allows precise point-to-point correlation between visual function and the macular pathology. However, precise delineation of CNV is a prerequisite for accurate correlation of the functional results with the CNV. • Methods: A total of 40 eyes with CNV secondary to age-related macular degeneration were evaluated with static manual microperimetry using the SLO to quantitate relative and absolute scotomata within the CNV. For precise delineation of the CNV, indocyanine green (ICG) angiography was simultaneously performed, allowing stimulus presentation at any desired retinal location under visual feedback of the angiogram. • Results: A relative scotoma was detected in 19 and an absolute scotoma in 21 out of 40 eyes. The depth of the scotomata was correlated with the duration of symptoms (P<0.01). Eyes with well-defined CNV had significantly deeper scotomas than eyes with occult CNV (P<0.005). • Conclusion: Microperimetry using the SLO and simultaneous ICG angiography demonstrated relative and absolute scotoma within the CNV. The depth of the scotoma may guide the ophthalmologist in selecting the adequate treatment.

Rate and timing of spontaneous resolution in a vitreomacular traction group: Should the role of watchful waiting be re-evaluated as an alternative to Ocriplasmin therapy?

Introduction The incidence of spontaneous resolution of vitreomacular traction (VMT) is low in studies of Ocriplasmin that have had a limited follow-up. Previous studies did not look for morphological parameters in the natural history using spectral-domain ocular coherence tomography (SD-OCT) imaging. The purpose of this study was to investigate how often and when spontaneous VMT resolution occurs in candidates for Ocriplasmin therapy. Methods The study is a retrospective chart review of patients who would have high chances of a benefit by an Ocriplasmin injection, without epiretinal membrane or vitreomacular adhesion of 1500 µm or more on SD-OCT. Main outcome measures were the frequency of complete VMT resolution and the best corrected visual acuity seen in the natural history. Results Out of the 46 patients that were included after screening 889 SD-OCT images, 20 were found to exhibit spontaneous resolution during the follow-up period (median: 594 days, 95% CI 567 to 719 days), the majority after 6–12 months of observation (95% CI 266 to 617 days). The group with spontaneous VMT resolution and a mean improvement of one line in best corrected visual acuity included a few patients losing vision by macular hole formation. In the absence of resolution, patients lost on average one early treatment diabetic retinopathy study letter per year. Younger age was found to increase the chance of spontaneous resolution. Conclusions A shorter follow-up might underestimate the incidence of spontaneous VMT resolution as the functional outcome of watchful waiting. The likelihood of resolution does not seem to decrease after 12 months.

Treatment of age-related macular degeneration: focus on ranibizumab

Ranibizumab, a humanized antigen-binding fragment (Fab) that binds all isoforms of VEGF-A, significantly slows down loss of vision and causes significant visual improvement in many patients with choroidal neovascularization (CNV) due to exudative age-related macular degeneration (AMD). These benefits of intravitreal ranibizumab apply to all angiographic subtypes of neovascular AMD and across all lesion sizes when the drug is injected at monthly intervals as shown in two pivotal phase III trials (ANCHOR and MARINA). The results from the PrONTO study suggest that less frequent treatment with ranibizumab through a variable dosing regimen dependent on optical coherence tomography (OCT) findings is a treatment option that results in comparably favorable visual outcomes. Currently, it is unclear whether combination therapy of ranibizumab with photodynamic therapy (PDT) provides any significant advantage over ranibizumab monotherapy (FOCUS trial); however, the combination of PDT and ranibizumab may decrease the need for frequent retreatment. This question will be addressed in the SUMMIT trial. Therapy with ranibizumab is generally very well tolerated with a low rate of seriously adverse ocular events or systemic side-effects. The advent of vascular endothelial growth factor (VEGF) inhibitors has revolutionized the therapy of neovascular AMD. Ranibizumab at the moment appears to be the most effective approved treatment for neovascular AMD.