Retinal Nerve Fiber Layer Thickness in Patients Receiving Chronic Anti–Vascular Endothelial Growth Factor Therapy




Purpose


To evaluate the effects of multiple intravitreal injections of anti–vascular endothelial growth factor (VEGF) agents on the thickness of the retinal nerve fiber layer (RNFL) in patients with wet age-related macular degeneration (ARMD).


Design


Retrospective, observational, consecutive case series of patients diagnosed with wet ARMD.


Methods


Forty-one eyes of 37 consecutive patients (25 female and 12 male; mean age 79.2 ± 8.7 years) who underwent treatment with pegaptanib, bevacizumab, and/or ranibizumab for ARMD 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.


Results


Average follow-up for all patients was 27.0 ± 9.7 months and they received an average of 16.0 ± 5.5 intravitreal injections. The average RNFL thickness at presentation was 92.4 ± 15.2 μm and at last follow-up was 93.8 ± 15.2 μm ( P = .68). There were no statistically significant differences in RNFL measurements when comparing between individual anti-VEGF treatment groups.


Conclusion


Long-term treatment with anti-VEGF agents did not lead to significant changes in RNFL thickness in a patient population with wet ARMD. 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. Further prospective studies with longer follow-up are needed to corroborate the findings of this study.


Upregulation of vascular endothelial growth factor (VEGF) has been correlated with the choroidal neovascular membranes seen in patients with wet age-related macular degeneration (ARMD). The use of intravitreal anti-VEGF agents has become the standard of care for patients with ARMD and these agents are now commonly used for various neovascular diseases of the eye. The duration of efficacy of the anti-VEGF agents pegaptanib (Macugen; EyeTech Pharmaceuticals/Pfizer Inc, New York, New York, USA), bevacizumab (Avastin; Genentech, Inc, San Francisco, California, USA), and ranibizumab (Lucentis; Genentech, Inc) is limited. Therefore, repeated injections are required to maintain their anti-angiogenic effects. While the use of anti-VEGF agents in clinical practice has increased, long-term safety data are still being published, and the full implications of repeated injections of protein-based therapeutics into the vitreous cavity remain unclear.


VEGF is known to be neurotrophic. Theoretically, chronic suppression of a neurotrophic cytokine may result in deleterious downstream 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 well known. The current study investigates the changes in RNFL measurements in ARMD patients treated with intravitreal pegaptanib, bevacizumab, and/or ranibizumab.


Methods


This is a retrospective, observational, consecutive case series of patients who had received more than 10 intravitreal injections of pegaptanib sodium, bevacizumab, ranibizumab, or a combination of these anti-VEGF agents at the Rocky Mountain Lions Eye Institute, University of Colorado Department of Ophthalmology. All patients who had a diagnosis of ARMD receiving anti-VEGF therapy between June 2005 and January 2008 were identified and those with documented RNFL thickness measurement by optical coherence tomography (OCT) (Stratus Carl Zeiss Meditec, Inc, Dublin, California, USA) prior to their first anti-VEGF injection were selected for initial evaluation. Peripapillary RNFL thickness scans were obtained at the same time as macular scans for ARMD by one of our retina specialists (N.M.) as part of an unrelated study focused on normative data for OCT. We then requested institutional review board permission to collect and analyze the OCT data for the purposes of our study. Patients with a history of open-angle glaucoma, angle-closure glaucoma, or pseudoexfoliation, as well as glaucoma suspects, were excluded. Patients who had more than 12 months of follow-up were included in the final analysis. RNFL OCT measurements were available for each follow-up, but only completed scans from the first and final follow-up visits were used for our analyses. All scans were evaluated to ensure that the RNFL was accurately identified and that the signal strength scores were all equal to or above 6.


Patients were divided into 3 groups. The first included all patients who fit the inclusion criteria regardless of anti-VEGF agent used. Group 2 consisted of patients who received at least 10 injections of ranibizumab alone. Group 3 had greater than 10 total injections of ranibizumab and bevacizumab. Statistical comparisons were done with the unpaired 2-tailed Student t test. Continuous variables were described as mean ± standard deviation (SD). A P value of ≤ .05 was considered to be statistically significant.




Results


Records were available for 184 patients who had received intravitreal anti-VEGF agents between 2005 and 2008 at the University of Colorado. Of these, 119 received injections for the diagnosis of wet ARMD. Fifty-five patients had received more than 10 intravitreal injections of anti-VEGF agents. There were 37 patients who had more than 1 year of follow-up and an RNFL measurement by OCT before their first injection and at last follow-up visit. A total of 41 eyes of these 37 consecutive patients (25 female and 12 male; mean age 79.2 ± 8.7 years) were included in our analyses ( Table ). None of the patients had a history of glaucoma and there were no cases of sustained IOP elevation for any of the patients during the study period.



TABLE

Retinal Nerve Fiber Layer Thickness After Anti-Vascular Endothelial Growth Factor Injections




































Number of Eyes Agent(s) Used Injections a Average Follow-up (Months) Change in RNFL Measurements b P Value
Group 1 41 Any 16.0 27.0 +1.42 .68
Group 2 21 R 13.4 20.1 +5.88 .35
Group 3 11 R, B 17.7 27.1 −1.04 .74

B = bevacizumab; R = ranibizumab; RNFL = retinal nerve fiber layer.

a Average number of anti-VEGF injections received.


b Average change between preinjection and final RNFL thickness in μm for the eyes treated with the designated anti-VEGF agent(s).



Group 1 (All Patients)


For all 41 eyes studied, there was an average follow-up of 27.0 ± 9.7 months (mean ± SD) and 16.0 ± 5.5 intravitreal injections. The average RNFL at presentation was 92.4 ± 15.2 μm; that increased to 93.8 ± 15.2 μm at last follow-up ( P = .68). Of these patients, there were 12 who received ranibizumab alone; 11 who received ranibizumab and bevacizumab; 5 who received ranibizumab, bevacizumab, and pegaptanib; and 4 who received ranibizumab and pegaptanib.


Group 2 (Ranibizumab Alone)


There was an average follow-up of 20.1 ± 3.6 months for the 21 eyes analyzed. The average number of injections was 13.4 ± 3.6. The average RNFL at presentation was 91.7 ± 16.4 μm; that increased to 97.6 ± 13.7 μm at last follow-up ( P = .35).


Group 3 (Combination Ranibizumab and Bevacizumab)


There was an average follow-up of 27.1 ± 4.2 months for the 11 eyes analyzed. The average number of injections was 17.7 ± 3.7. The average RNFL at presentation was 96.4 ± 12.9 μm; that decreased to 95.4 ± 13.5 μm at last follow-up ( P = .74).

Only gold members can continue reading. Log In or Register to continue

Jan 17, 2017 | Posted by in OPHTHALMOLOGY | Comments Off on Retinal Nerve Fiber Layer Thickness in Patients Receiving Chronic Anti–Vascular Endothelial Growth Factor Therapy
Premium Wordpress Themes by UFO Themes