MyVisionTest News Archive
Aug 25, 2010
anti-VEGF therapy safe for retinal nerve fiber layer
Long-term intravitreal injection of anti–vascular endothelial growth factor (VEGF) agents does not adversely affect on the thickness of the retinal nerve fiber layer (RNFL) in patients with wet age-related macular degeneration (AMD).
The use of intravitreal anti-VEGF agents has become the standard of care for patients with AMD. The duration of action of the currently available anti-VEGF agents is limited. Therefore, repeated injections are required to maintain their anti-angiogenic effects. The full safety implications of frequent injections of anti-VEGF drugs into the vitreous cavity is unknown.
VEGF has neurotrophic properties, meaning it helps to maintain the health of nerve cells. Theoretically, chronic suppression of a neurotrophic cytokine may result in deleterious effects on the retinal nerve fiber layer (RNFL). In addition, there have been reports relating intravitreal injection of anti-VEGF agents to both transient and sustained elevation of intraocular pressure (IOP). The long-term effects of repeated anti-VEGF injections, as they relate to neurotrophic properties and IOP fluctuations, on RNFL thickness are not known.
Methods and Results
In this retrospective case series 41 eyes of 37 consecutive patients (25 female and 12 male; mean age 79.2 ± 8.7 years) who underwent treatment with Macugen (pegaptanib), Avastin (bevacizumab), and/or Lucentis (ranibizumab) for AMD followed by sequential RNFL thickness measurement by optical coherence tomography (OCT) were studied. Patients were included in the analyses if they had greater than 10 total anti-VEGF injections, RNFL measurements prior to the first injection, and at least 12 months of follow-up. Patients were divided into 3 groups depending on which anti-VEGF agent(s) they received. The OCT RNFL measurements at the initial and final follow-up were used for analyses.
Average follow-up for all patients was 27 months and they received an average of 16.0 intravitreal injections. The average RNFL thickness at presentation was 92.4 µm and at last follow-up was 93.8 µm. There were no statistically significant differences in RNFL measurements when comparing between individual anti-VEGF treatment groups.
Discussion and Conclusions
Multiple studies have shown that there is an IOP elevation associated with intraocular injections of anti-VEGF agents. This IOP elevation has been shown to fall below 30 mm Hg by 30 minutes and back to baseline by 30 to 60 minutes for most patients. Episodic IOP fluctuations are a potential risk factor for the progression of glaucomatous damage to the optic nerve head. Therefore, long-term injections every 4 to 6 weeks of an anti-VEGF agent could potentially damage the RNFL. Our results did not support this theory since we found no statistical differences in RNFL thickness before and after chronic use of anti-VEGF agents.
There have been reports documenting sustained IOP elevations weeks and even months after initial or repeated intravitreal injection(s) of anti-VEGF agents. It has been postulated that the sustained IOP elevation could be related to trabecular meshwork obstruction from the anti-VEGF agents or impurities within injected fluid, or could be a result of an intraocular inflammatory response. None of the patients involved in this retrospective review had episodes of sustained increases in IOP.
In addition to its angiogenic role, VEGF-A has a neuoprotective function. Zachary (2005) described VEGF-A as having both a neurotrophic and neuroprotective effect on glial cells. Other research has implicated a decreased level of VEGF in neuronal degeneration by possibly limiting perfusion as well as halting VEGF-A's neurotrophic properties. By inhibiting VEGF-A, the chronic use of anti-VEGF agents could potentially lead to RNFL thinning. The current study found that long-term (27 month) follow-up of patients post anti-VEGF injection had no effect on OCT RNFL thickness.
The researchers conclude that long-term treatment with anti-VEGF agents did not lead to significant changes in RNFL thickness in a patient population with wet AMD. Despite the possibility of repeated intraocular pressure (IOP) fluctuations after intravitreal injections and known neurotrophic properties of VEGF in the eye, chronic therapy with intravitreal anti-VEGF agents does not appear to adversely affect RNFL thickness.
Read more...
Am J Ophthalmol. 2010 Jul 17. [Epub ahead of print]
Tags: VEGF, neuroprotection, adverse drug effects
Long-term intravitreal injection of anti–vascular endothelial growth factor (VEGF) agents does not adversely affect on the thickness of the retinal nerve fiber layer (RNFL) in patients with wet age-related macular degeneration (AMD).The use of intravitreal anti-VEGF agents has become the standard of care for patients with AMD. The duration of action of the currently available anti-VEGF agents is limited. Therefore, repeated injections are required to maintain their anti-angiogenic effects. The full safety implications of frequent injections of anti-VEGF drugs into the vitreous cavity is unknown.
Methods and Results
In this retrospective case series 41 eyes of 37 consecutive patients (25 female and 12 male; mean age 79.2 ± 8.7 years) who underwent treatment with Macugen (pegaptanib), Avastin (bevacizumab), and/or Lucentis (ranibizumab) for AMD followed by sequential RNFL thickness measurement by optical coherence tomography (OCT) were studied. Patients were included in the analyses if they had greater than 10 total anti-VEGF injections, RNFL measurements prior to the first injection, and at least 12 months of follow-up. Patients were divided into 3 groups depending on which anti-VEGF agent(s) they received. The OCT RNFL measurements at the initial and final follow-up were used for analyses.
Average follow-up for all patients was 27 months and they received an average of 16.0 intravitreal injections. The average RNFL thickness at presentation was 92.4 µm and at last follow-up was 93.8 µm. There were no statistically significant differences in RNFL measurements when comparing between individual anti-VEGF treatment groups.
Discussion and Conclusions
Multiple studies have shown that there is an IOP elevation associated with intraocular injections of anti-VEGF agents. This IOP elevation has been shown to fall below 30 mm Hg by 30 minutes and back to baseline by 30 to 60 minutes for most patients. Episodic IOP fluctuations are a potential risk factor for the progression of glaucomatous damage to the optic nerve head. Therefore, long-term injections every 4 to 6 weeks of an anti-VEGF agent could potentially damage the RNFL. Our results did not support this theory since we found no statistical differences in RNFL thickness before and after chronic use of anti-VEGF agents.
There have been reports documenting sustained IOP elevations weeks and even months after initial or repeated intravitreal injection(s) of anti-VEGF agents. It has been postulated that the sustained IOP elevation could be related to trabecular meshwork obstruction from the anti-VEGF agents or impurities within injected fluid, or could be a result of an intraocular inflammatory response. None of the patients involved in this retrospective review had episodes of sustained increases in IOP.
In addition to its angiogenic role, VEGF-A has a neuoprotective function. Zachary (2005) described VEGF-A as having both a neurotrophic and neuroprotective effect on glial cells. Other research has implicated a decreased level of VEGF in neuronal degeneration by possibly limiting perfusion as well as halting VEGF-A's neurotrophic properties. By inhibiting VEGF-A, the chronic use of anti-VEGF agents could potentially lead to RNFL thinning. The current study found that long-term (27 month) follow-up of patients post anti-VEGF injection had no effect on OCT RNFL thickness.
The researchers conclude that long-term treatment with anti-VEGF agents did not lead to significant changes in RNFL thickness in a patient population with wet AMD. Despite the possibility of repeated intraocular pressure (IOP) fluctuations after intravitreal injections and known neurotrophic properties of VEGF in the eye, chronic therapy with intravitreal anti-VEGF agents does not appear to adversely affect RNFL thickness.
Read more...
Am J Ophthalmol. 2010 Jul 17. [Epub ahead of print]
