Intravitreal anti-VEGF Treatment in Central Retinal Vein Occlusion (CRVO): a Meta-Analysis of One Year Results.

Background It was the aim of this meta-analysis to assess the 12-month efficacy of intravitreal anti-vascular endothelial growth factor therapy in eyes with central retinal vein occlusion. Patients and Methods A MEDLINE-based survey was performed, including 33 publications (27 case series), covering a total of 1834 treated eyes. Baseline data (age, length of symptoms, visual acuity, gain in visual acuity at 3, 6, and 12 months) and average numbers of injections were calculated. Linear and non-linear regressions were calculated to relate baseline and treatment parameters and outcome. In a subgroup analysis, outcome data of randomised and non-randomised studies were compared. Results Mean gain in visual acuity was 2.8 ± 0.8 (mean±1 standard deviation), 2.7 ± 1.1 and 2.2 ± 1.4 lines at months 3, 6, and 12. 4.2 ± 1.2 and 6.4 ± 2.4 injections were given until months 6 and 12. Visual acuity gain improved significantly more in randomised trials (3.3 ± 0.7 and 3.0 ± 0.4, at months 6 and 12 versus 2.4 ± 1.1 and 2.2 ± 1.4, both p = 0.04) than in non-randomised studies. Eyes in randomised trials received significantly more injections (4.8 ± 1.1 and 8.6 ± 0.7 until month 6 and 12 versus 3.7 ± 1.0 and 5.6 ± 2.3, p = 0.045 and 0.04). After 12 months of care, the improvement in visual acuity was significantly correlating to the number of injections given. The dose response curve suggests saturation with treatment at an average of 7-8 injections within 12 months. The midpoint of the dose response curve was calculated at 6.78 injections per year. Conclusions The results of this analysis show that an improvement of approximately 3 lines can be maintained in the first year. Careful observation seems necessary to avoid under-treatment, which may occur below an average of 7-8 injections within the first 12 months of treatment.

Combined Laser Photocoagulation and anti-VEGF Injection Treatment in Radiation Retinopathy.

Background Radiation retinopathy can lead to a considerable reduction in visual acuity. We report 2 cases of radiation retinopathy in which a therapy with combined intravitreal anti-VEGF injection and laser photocoagulation (LPC) was used. Patient History Two 55-year-old women were referred to our clinic with radiation retinopathy, in the first case unilaterally after radiation due to endocrine orbitopathy (P1), in the second case in both eyes after palliative cerebral radiation for metastatic breast cancer (P2). Both cases were treated with combined intravitreal anti-VEGF injection and focal LPC. Therapy After the initiation therapy macular edema decreased considerably. One year after the beginning of therapy visual acuity increased in the first case from 0,05 to 0,16 p, in the second case from 0,5/0,4 to 0,6/0,5. Despite the positive response there is still continuing need for therapy in all three eyes. Conclusions Combined anti-VEGF injection and LT can reduce macular edema due to radiation retinopathy. The follow-up observation shows the necessity of long-term care.

6-Year Results of CNV Secondary to Pathological Myopia Treated with Ranibizumab.

Background The current standard treatment of choroidal neovascularisation (CNV) secondary to pathological myopia (PM) is intravitreal injection of VEGF antagonists. We now present our 6-year results after treating patients with CNV secondary to PM with ranibizumab. Patients and Methods We retrospectively analysed 15 treatment-naive eyes of 13 patients (10 women, 3 men, mean age 59.2; standard deviation (SD) 11.1; range 41-78 years) with visual impairment related to CNV secondary to PM, who were treated with at least 1 injection of ranibizumab. Follow-up treatments were indicated according to our PRN (pro re nata) regimen. Re-treatment criteria were: reduction in visual acuity and/or activity in OCT or fluorescence angiography. Results Patients received a mean of 3.5 ranibizumab injections (SD 3.4; range 1-12) during a mean follow-up of 85 months (SD 6.6; range 76-102 months). Initial spherical equivalent was - 12.4 ± 4.0 dpt (range - 7.5 to 20.5 dpt). Baseline visual acuity was (log MAR) 0.65 ± 0.28. After one month, visual acuity improved to 0.43 ± 0.23 (p = 0.002), after 3 months to 0.38 ± 0.22 (p = 0.002), after 6 months to 0.34 ± 0.22 (p = 0.002) and after 9 months to 0.35 ± 0.23 (p = 0.002). After 1 year, visual acuity was 0.35 ± 0.24 (p = 0.001), after 2 years 2 0.35 ± 0.23 (p = 0.001), after 3 years 0.35 ± 0.23 (p = 0.002), after 4 years 0.37 ± 0.23 (p = 0.002), after 5 years 0.38 ± 0.23 (p = 0.002), and after 6 years 0.39 ± 0.26 (p = 0.016). Conclusion After considerable initial improvement in visual acuity, the initial gain was maintained by a strict PRN regimen for the observation and treatment of patients with neovascular membranes secondary to pathological myopia. The number of injections needed to achieve stable visual acuity was lower than with other diseases that respond to anti-VEGF.

Results of a Meta-Analysis on Intravitreal anti-VEGF Treatment of Macular Oedema Secondary to Branch Retinal Vein Occlusion (BRVO).

Background In this meta-analysis, the outcome was analysed of intravitreal anti-VEGF (vascular endothelial growth factor) ocular therapy of macular oedema secondary to branch retinal vein occlusion; this was related to baseline and treatment parameters. Material and Methods 36 relevant publications (33 case series) were identified in a MEDLINE-based literature search, which reported on 1,759 treated eyes. Statistical analysis included description of baseline, treatment, and outcome data, linear and non-linear regression and comparison of randomised and non-randomised studies. Results The mean improvement in visual acuity (VA) was 2.8 ± 0.9 lines (mean ± 1 standard deviation) at month 3, 3.1 ± 0.8 at month 6, and 3.2 ± 0.8 lines at month 12. The mean number of anti-VEGF injections was 3.8 ± 1.3 until month 6, and 4.1 ± 2.3 until month 12. Eyes in randomised trials received significantly more injections (4.8+/1.2) than those in non-randomised studies (2.9 ± 0.6, p = 0.0126) until month 6. At months 6 and 12, the gain in visual acuity was not significantly different between randomised and non-randomised studies (3.2 ± 0.4 versus 3.1 ± 1.0 lines, and 3.3 ± 0.4 versus 3.2 ± 1.0, respectively). Regression analysis did not indicate a significant relationship between the number of injections and the improvement in visual acuity at months 6 and 12. Visual acuity outcome was significantly worse in older patients at months 3, 6, and 12. Conclusions The results of this meta-analysis demonstrate that a substantially improved and favourable absolute visual acuity can be achieved with relatively few anti-VEGF injections in eyes with branch retinal vein occlusion.

[Endonasal Dacryocystorhinostomy (DCR) with Transcanalicular Endoillumination (TCE) of the Saccus Lacrimalis]. / Endonasale Dacryozystorhinostomie (DCR) mit transkanalikulärer Endoillumination (TCE) des Saccus lacrimalis.

Endonasal dacryocystorhinostomy (DCR) has been established as a standard procedure of lacrimal surgery, since it causes much less tissue damage than ab externo procedures. Diffiulties in visualization of the target area has been a limitation to the transnasal approach. An improvement of the classical endonasal DCR was achieved by the introduction of a transcanalicular endoillumination (TCE) of the lacrimal sac using a 23-Gauge vitreoretinal light probe, which can easily be intubated into the cannaliculi and advanced into the the lacrimal sac. Illumination of the lacrimal sac guides the endonasal approach and facilitates the creation of a lacrimal bypass. In our standard procedure a bicanalicular silicone intubation through the osteotomy is finally placed. Due to the introduction of TCE of the lacrimal sac, the surgical procedure of endonasal DCR became less traumatic and needed a significantly reduced operating time.

Transient Subfoveal Fluid and Visual Loss after Ocriplasmin.

BACKGROUND: Intravitreal injection of ocriplasmin for the enzymatic resolution of vitreomacular traction was approved for the EU in 2013. We wish to report our clinical findings and adverse effects that were not observed in the registration trial. THERAPY AND OUTCOME: In 5 of our first 12 consecutive cases, resolution of the vitreomacular traction occurred after injecting ocriplasmin. 9 of the 12 patients developed subfoveal fluid, manifest at day 3 post-intervention; this was completely re-absorbed by 6 weeks in 8 of 9 eyes. All 9 cases with subretinal fluid exhibited a significant reduction in mean visual acuity at the first visit, of 0.33 LogMAR (p = 0.008, Wilcoxon signed rank test). After regression of the subretinal fluid, visual acuity returned to the baseline value. CONCLUSIONS: In the light of the documented adverse effects of the registration trial, the relatively high rate of subfoveal fluid after injecting ocriplasmin was surprising. Possible causes include enzymatic lysis of the matrix between the outer segments of the photoreceptors and the microvilli of the RPE-cells, or barrier disturbances in the RPE through lysis of the zonulae occludentes.

Acid Violet 17: a New Dye for Chromovitrectomy?

BACKGROUND: Acid violet 17 (AV17) has recently received CE certification as a dye for intraocular use during vitreoretinal interventions. This publication reviews the available preclinical and clinical data on the use of this new dye. MATERIAL AND METHODS: A systematic MEDLINE literature search was conducted on preclinical testing, clinical testing, and application of AV17 in ocular cell cultures, organ cultures, or ex vivo and in vivo ocular surgical procedures. RESULTS: Of the 59 primary hits, 5 publications (4 preclinical, 1 clinical) were identified as reporting relevant data. All available results on preclinical testing referred to concentrations of AV17 much lower (0.005 to 1.0 mg/ml) than the presently marketed dye (1.5 mg/ml, ala purple, ala®medics, Dornstadt/Germany). Toxic or undesired effects of AV17 on different ocular structures or cells were observed under the following conditions: retinal pigment epithelium: 0.25 mg/ml, 180 seconds, 0.05 mg/ml, 1800 seconds; ganglion cell viability: 0.25 mg/ml, 30 seconds; Müller cell activation: 0.25 mg/ml, 30 seconds; astrocyte activation 0.5 mg/ml, 30 seconds; microglia activation: 0.5 mg/ml, 300 seconds. No adverse effects were observed in a clinical case series of macular hole surgery (Peel et al. 2015). In this series, the dye was not applied as described in the label. In our own clinical experience, two different undesired effects were observed: transient discolouration of hydrophilic intraocular lenses and degeneration of the RPE in cases of macular hole surgery. CONCLUSIONS: Preclinical tests indicate that AV17 has toxic and undesired effects at concentrations much lower than claimed by suppliers. Against the background of these data and the first observations of adverse clinical effects, it seems advisable to be cautious when using AV17.

Long-term Results of Intravitreal Anti-VEGF Injections in Wet AMD: A Meta-Analysis.

BACKGROUND: Although intravitreal anti-VEGF medications are widely used in age-related macular degeneration, no systematic data analysis is available on the long-term prognosis of this relatively new therapeutic approach. MATERIAL AND METHODS: A meta-analysis was performed on available Medline literature. 13 relevant clinical studies (14 case series) could be identified, covering 10 247 treated eyes. The majority of available reports originate from single centre retrospective real-life environments. RESULTS: The mean improvement in average visual gain was 0.9 ± 0.5 (mean ± 1 standard deviation, median; 0.8 lines) at year 1, 1.2 ± 1.1 (median: 1.1) letters at year 2, 0.7 ± 1.0 (median: 0.7) letters at year 3, and 0.2 ± 0.8 (median: 0.5), 0.4 ± 0.4 (median: 0.5) at years 4 and 5. The drop-out rates in these studies was relatively high. At the end of year 3, the average percentage of observed eyes was 44.3 ± 18.4 % (mean ± 1 standard deviation), at the end of year 4 23.5 ± 23.9 % and after years 6 and 7 below 10 % (8.2 and 7.9 %). The mean treatment frequency of injections in all available studies was highest in year 1 (6.4 ± 1.2, 6.1 - mean ± SD; median), followed by relatively consistent mean values of 4.1 and 5.1 (year (Y)2: 4.4, Y3: 4.3, Y4: 4.7, Y5: 4.1, Y6: 5.1, Y7: 4.7) injections per year. CONCLUSIONS: The results of this meta-analysis clearly indicate that intravitreal anti-VEGF injection therapy is capable of maintaining visual acuity on a long-term basis of at least 4-5 years.