Sirolimus With the release of Aflibercept with times affinity to

With the release of Aflibercept with 100 times affinity to VEGF, many authors introduced this new drug in cases with no response to Ranibizumab, with variable results.
In a retrospective review at Ophthalmic Consultants of Boston, Cho et al. evaluated the anatomical and visual effect of intravitreal Aflibercept 2.0mg in cases of exudative age-related macular degeneration (AMD) with persistent fluid on optical coherence tomography (OCT) despite regular Ranibizumab 0.5mg and/or Bevacizumab 1.25mg treatment at 1 and 6months.
They included a total of 353 eyes with exudative AMD that were switched to Aflibercept during the study period. Of these, 28 eyes in 28 patients had persistent fluid after an average of 20 regular Ranibizumab/Bevacizumab injections (range 7–37). At 1month, 89% (25 eyes) showed anatomical improvement and 18% (five eyes) were dry after a single Aflibercept injection. Central subfoveal thickness improved from 295 to 272μm (p<0.001) after one Aflibercept injection. After an average of 4.4 Aflibercept injections (range 3–6) over 6months, the central subfoveal thickness remained improved (274μm, p=0.008); 64% (18 eyes) showed anatomical improvement and a quarter of eyes (25%, seven eyes) were dry. Visual acuity did not improve at 1month (Log MAR 0.54, p=0.64) or 6months (Log MAR 0.57, p=0.49). Despite no improvement in visual acuity, a significant proportion of cases responded anatomically to Aflibercept 2.0mg. Bakall et al. conducted a retrospective chart review looking for Ranibizumab/ Bevacizumab resistant cases and identified 36 eyes from 31 patients. There were 13 male and 18 female patients. The number of prior injections with either Bevacizumab or Ranibizumab ranged from 6 to 74. After 3 monthly injections of Aflibercept, there was a Sirolimus in either subretinal or intraretinal fluid in 18 of 36 (50.0%) of the treated eyes; the amount of fluid remained stable in 15 eyes (41.7%) and worsened in 3 eyes (8.3%). A significant average decrease was observed for the central macular thickness after 3 injections of 65μm, with no significant change in visual acuity.
In addition to Aflibercept, the 2mg dose of Ranibizumab was the subject of a trial in patients recalcitrant to ranibizumab 0.5mg dose. This Phase I-II trial of 88 patients with recalcitrant neovascular AMD treated as needed for every 4 (cohort A) or 6weeks (cohort B) following three monthly doses. 79 patients completed the 12-month endpoint and were given 11.6 (cohort A) and 8.6 (cohort B) mean treatments. Mean best corrected visual acuity gains of 4.1 letters following three monthly doses were sustained for 12months for both cohorts. Anatomical improvements were sustained for 12months for cohort A, but not for cohort B; cohort B demonstrated a gradual increase in mean central retinal thickness (p=0.03).
The interesting fact in this trial is that visual and anatomical gains achieved with 2.0mg Ranibizumab in recalcitrant neovascular AMD were sustained for 1year only with monthly treatment. In comparison, anatomical gains were reduced with less than monthly treatment.


Conflict of interest

Haemodialysis (HD) is the unique treatment modality for end stage chronic renal failure patients until the possible renal transplantation. With HD lots of alterations occur in patients’ haemostasis and metabolic parameters. These alterations effect eye and may cause some pathologies such as refractive changes, dry eye, band keratopathy and some neuroophthalmologic complications.

Material and method
All patients received 4h HD each session and 3 times per week. The reason of chronic renal failure, duration of haemodialysis and the presence of diabetes mellitus (DM) were recorded. Systolic and diastolic arterial pressure of each patient was measured before and after HD session. After that mean arterial pressure (MAP) was calculated.
OCT images were acquired by an experienced technician. The patients’ pupil were undilated during measurement. We used Cirrus SD-OCT (Carl Zeiss Meditec, Dublin, CA, USA) in this study. Measurements were acquired before and immediately after (max. 30min.) HD session. Central subfield thickness, central foveal thickness, average ganglion cell layer thickness and RNFL thickness were recorded by OCT measurements.