Blocking Ocular Sympathetic Activity Inhibits Choroidal Neovascularization.

Purpose: To investigate how modulating ocular sympathetic activity affects progression of choroidal neovascularization (CNV), a hallmark feature of wet age-related macular degeneration (AMD). Methods: In the first of two studies, Brown Norway rats underwent laser-induced CNV and were assigned to one of the following groups: daily eye drops of artificial tears (n = 10; control group); daily eye drops of the ß-adrenoreceptor agonist isoproterenol (n = 10); daily eye drops of the ß-adrenoreceptor antagonist propranolol (n = 10); sympathetic internal carotid nerve (ICN) transection 6 weeks prior to laser-induced CNV (n = 10). In the second study, rats underwent laser-induced CNV followed by ICN transection at different time points: immediately after the laser injury (n = 6), 7 days after the laser injury (n = 6), and sham surgery 7 days after the laser injury (n = 6; control group). All animals were euthanized 14 days after laser application. CNV development was quantified with fluorescein angiography and optical coherence tomography (in vivo), as well as lesion volume analysis using 3D confocal reconstruction (postmortem). Angiogenic growth factor protein levels in the choroid were measured with ELISA. Results: In the first study, blocking ocular sympathetic activity through pharmacological or surgical manipulation led to a 75% or 70% reduction in CNV lesion volume versus the control group, respectively (P < 0.001). Stimulating ocular sympathetic activity with isoproterenol also led to a reduction in lesion volume, but only by 27% versus controls (P < 0.05). VEGF protein levels in the choroid were elevated in the three treatment groups (P < 0.01). In the second study, fluorescein angiography and CNV lesion volume analysis indicated that surgically removing the ocular sympathetic supply inhibited progression of laser-induced CNV, regardless of whether ICN transection was performed on the same day or 7 days after the laser injury. Conclusion: Surgical and pharmacological block of ocular sympathetic activity can inhibit progression of CNV in a rat model. Therefore, electrical block of ICN activity could be a potential bioelectronic medicine strategy for treating wet AMD.

Sympathetic Effects of Internal Carotid Nerve Manipulation on Choroidal Vascularity and Related Measures.

Purpose: To investigate specific effects of denervation and stimulation of the internal carotid nerve (ICN) on the choroid and retina. Methods: Female Sprague Dawley rats underwent unilateral ICN transection (n = 20) or acute ICN electrical stimulation (n = 7). Rats in the denervation group were euthanized 6 weeks after nerve transection, and eyes were analyzed for changes in choroidal vascularity (via histomorphometry) or angiogenic growth factors and inflammatory markers (via ELISA). Rats in the stimulation group received acute ICN electrical stimulation with a bipolar cuff electrode over a range of stimulus amplitudes, frequencies, and pulse widths. Choroidal blood flow and pupil diameter were monitored before, during, and after stimulation. Results: Six weeks after unilateral ICN transection, sympathectomized choroids exhibited increased vascularity, defined as the percentage of choroidal surface area occupied by blood vessel lumina. Vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR-2) protein levels in denervated choroids were 61% and 124% higher than in contralateral choroids, respectively. TNF-α levels in denervated retinas increased by 3.3-fold relative to levels in contralateral retinas. In animals undergoing acute ICN electrical stimulation, mydriasis and reduced choroidal blood flow were observed in the ipsilateral eye. The magnitude of the reduction in blood flow correlated positively with stimulus frequency. Conclusions: Modulation of ICN activity reveals a potential role of the ocular sympathetic system in regulating endpoints related to neovascular diseases of the eye.

Stereological Method in Optical Coherence Tomography for In Vivo Evaluation of Laser-Induced Choroidal Neovascularization.

BACKGROUND AND OBJECTIVE: To evaluate a stereological method in optical coherence tomography (OCT) as an in vivo volume measurement of laser-induced choroidal neovascularization (L-CNV) lesion size. PATIENTS AND METHODS: Laser photocoagulation was applied in rats to rupture Bruch's membrane and induce L-CNV. In vivo OCT images of neovascular lesions were acquired with a spectral-domain OCT system at days 0, 3, 7, 10, and 14 after laser surgery. A stereological image-processing method was used to calculate lesion volumes from the OCT images. Rats were euthanized at day 14, and confocal microscopy was used to obtain accurate volume measurements of the lesions ex vivo. Lesion sizes calculated from OCT and confocal were compared. RESULTS: In vivo assessment by OCT allowed three distinct stages of L-CNV to be visualized: the initial early reaction, neovascular proliferation, and regression. At day 14, correlations between OCT and confocal lesion volumes showed a positive association (Pearson's r = 0.50, P < .01). Except for the largest lesions, volumes measured by OCT were statistically similar to those measured by the confocal gold standard (P = .90). CONCLUSION: The stereological approach used to measure neovascular lesion volume from OCT images offers an accurate means to track L-CNV lesion size in vivo. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e65-e74.].

Feasibility and safety of vitrectomy under topical anesthesia in an office-based setting.

Purpose: The purpose of this study was to evaluate the feasibility and safety of office-based vitreoretinal procedures. Methods: Patients undergoing primary elective pars plana vitrectomy were elected for surgery in an office-based setting (performed in a minor procedure room under topical anesthesia [TA] and oral anxiolysis). Rates of surgical objective achievement, surgical timing, and comfort were recorded to evaluate feasibility. Intraoperative and postoperative adverse events were assessed to evaluate safety. Results: Office-based vitrectomy surgery was performed in 34 eyes of 30 patients. The mean surgical time was 12.351 ± 8.21 min. Surgical objectives were achieved in 100% of cases. The mean best-corrected visual acuity improvement was 9.08 letters (P < 0.0001). During most parts of the procedure, no patient reported pain or discomfort. Neither intraoperative nor postoperative adverse events were reported until the final follow-up visit. Conclusion: Office-based vitreoretinal procedures under TA could be as feasible and as safe as vitreoretinal procedures under conventional anesthesia.