Review of intravitreal VEGF inhibitor toxicity and report of collapsing FSGS with TMA in a patient with age-related macular degeneration.

Intravitreal vascular endothelial growth factor (VEGF) receptor blockade is used for a variety of retinal pathologies. These include age-related macular degeneration (AMD), diabetic macular edema (DME) and central retinal vein obstruction. Reports of absorption of intravitreal agents into systemic circulation have increased in number and confirmation of depletion of VEGF has been confirmed. Increasingly there are studies and case reports showing worsening hypertension, proteinuria, renal dysfunction and glomerular disease. The pathognomonic findings of systemic VEGF blockade, thrombotic microangiopathies (TMAs), are also being increasingly reported. One lesion that occurs in conjunction with TMAs that has been described is collapsing focal segmental glomerulosclerosis (cFSGS). cFSGS has been postulated to occur due to TMA-induced chronic glomerular hypoxia. In this updated review we discuss the mechanistic, pharmacological, epidemiological and clinical evidence of intravitreal VEGF toxicity. We review cases of biopsy-proven toxicity presented by our group and other investigators. We also present the third reported case of cFSGS in the setting of intravitreal VEGF blockade with a chronic TMA component that was crucially found on biopsy. This patient is a 74-year-old nondiabetic male receiving aflibercept for AMD. Of the two prior cases of cFSGS in the setting of VEGF blockade, one had AMD and the other had DME. This case solidifies the finding of cFSGS and its association with chronic TMA as a lesion that may be frequently encountered in patients receiving intravitreal VEGF inhibitors.

Relationship of cochlea with surrounding neurovascular structures and their implication in cochlear implantation.

PURPOSE: The purpose of this investigation was to evaluate the topographic relations of cochlea with vital neurovascular structures and their implications for cochlear implantation (CI). METHODS: Sixty cadaveric human temporal bones were microdissected to expose the basal turn (BT) of cochlea, the carotid canal, the facial canal (FC) and the jugular fossa (JF). The minimum distances of BT of the cochlea from the carotid canal, the FC and roof of the JF were measured. RESULTS: The mean minimum distances of BT of the cochlea from the carotid canal, the FC and roof of the JF were found to be 1.38 ± 0.82, 1.06 ± 0.46 and 4.68 ± 2.21 mm, respectively. The abutment and impingement of carotid canal on anterior cochlear wall was found in three (5 %) and six (10 %) cases, respectively. Thin bone separation was observed between cochlea and FC (0.1 mm) in one case (1.67 %). CONCLUSIONS: The preoperative knowledge of the variant anatomy of BT of cochlea in relation to adjacent vital structures like abutment and impingement of carotid canal and thin bone separation of the BT of cochlea from FC and JF is of immense importance in CI, which may otherwise lead to disastrous consequences during surgery.

Impingement of the carotid canal on the basal turn of the cochlea as pertaining to cochlear implantation.

HYPOTHESIS: To evaluate the relation of the basal turn of the cochlea with the carotid canal as pertaining to cochlear implantation. BACKGROUND: Cochlear implantation is an established mode of treatment for patients with bilateral profound sensorineural hearing loss. An intricate knowledge of both the typical and atypical topography of the cochlea with the carotid canal is essential for safely conducting cochlear implantation. DESIGN: Fifty-eight cadaveric temporal bones were microdissected to expose the medial wall of the middle ear. To open the basal turn of the cochlea, the promontory was drilled. The carotid canal was unroofed to reveal the internal carotid artery. The minimum distance between the basal turn of the cochlea and the vertical part of the carotid canal was measured. RESULTS: The minimum distance between the basal turn of the cochlea and the carotid canal ranged from 0 to 3.9 mm (mean ± SD, 1.3 ± 0.8 mm). The carotid canal was abutting the basal turn of the cochlea in three cases, and impingement of the carotid canal on the anterior cochlear wall was found in five (8.6%) cases. CONCLUSION: Preoperative knowledge of findings like impingement (8.6%) and abutment (5.2%) of the carotid canal on the basal turn of the cochlea is of immense importance in cochlear implantation, which may otherwise lead to disastrous consequences during surgery.