Quan V Hoang

Effect on Intraocular Pressure in Patients Receiving Unilateral Intravitreal Anti-Vascular Endothelial Growth Factor Injections

PURPOSE We assessed the frequency and predictive factors related to intraocular pressure (IOP) elevation in neovascular age-related macular degeneration (AMD) patients undergoing unilateral intravitreal ranibizumab and/or bevacizumab injections. DESIGN Retrospective cohort study. PARTICIPANTS Charts of 207 patients with neovascular AMD who presented to a single physician at a retinal referral practice over a 6-month period were retrospectively reviewed. METHODS Data recorded included demographic information, clinical findings, total number of bevacizumab and ranibizumab injections received and IOP at each visit. Increases above baseline IOP of >5, >10, or >15 mmHg on ≥2 consecutive visits while under treatment were noted. MAIN OUTCOME MEASURES The frequency of IOP elevation was compared between treated and untreated eyes. In addition, among treated eyes, frequency and odds ratio of experiencing IOP elevation >5 mmHg above baseline on ≥2 consecutive visits was stratified by number of injections. For the main regression analysis, the outcome variable was IOP elevation >5 mmHg on ≥2 consecutive visits and the main independent variable was total number of injections. RESULTS On ≥2 consecutive visits, 11.6% of treated versus 5.3% of untreated/control eyes experienced IOP elevation of >5 mmHg. The mean number of injections was higher in those with (24.4; 95% confidence interval [CI], 20.9-28.0; range, 9-39) than without IOP elevation of >5 mmHg (20.4; 95% CI, 18.9-21.8; range, 3-48) on ≥2 consecutive visits. There was an increased odds ratio (5.75; 95% CI, 1.19-27.8; P = 0.03) of experiencing IOP elevation >5 mmHg on ≥2 consecutive visits in patients receiving ≥29 injections compared with ≤12 injections. Of the factors considered, only the total number of injections showed a statistically significant association with IOP elevation >5 mmHg above baseline on ≥2 consecutive visits in treated eyes (P = 0.05). CONCLUSIONS A greater number of intravitreal anti-vasular endothelial growth factor injections is associated with an increased risk for IOP elevation >5 mmHg on ≥2 consecutive visits in eyes with neovascular AMD receiving intravitreal ranbizumab and/or bevacizumab.

Clinical predictors of sustained intraocular pressure elevation due to intravitreal anti-vascular endothelial growth factor therapy.

Purpose: We assess for frequency and predictive factors related to sustained intraocular pressure (IOP) elevation in eyes with neovascular age-related macular degeneration receiving intravitreal injections of ranibizumab and/or bevacizumab. Methods: A total of 328 patients with neovascular age-related macular degeneration (449 eyes) who presented to a single physician over a 6-month period were retrospectively assessed for baseline demographic/clinical information, total number of bevacizumab and/or ranibizumab injections, and sustained IOP elevation on 2 or more consecutive visits (absolute IOP >25 mmHg, increase above baseline >10 mmHg, or IOP of >21 mmHg and increase of >5 mmHg). Cox regression survival analysis and multivariate logistic regression were performed to assess the influence of intravitreal injections on experiencing sustained IOP elevation. Results: Overall, 32 eyes (7.1%) experienced sustained IOP elevation. Survival analysis showed a significant effect of the number of anti–vascular endothelial growth factor injections on sustained IOP elevation (hazard ratio, 1.085; 95% confidence interval: 1.06–1.11, P < 0.001). Also, there was an increased odds ratio (16.1, P = 0.008) of sustained IOP elevation in eyes receiving ≥29 injections compared with ⩽12 injections. After controlling for the confounder (prior intravitreal steroid injection), total number of injections still showed a statistically significant association (P = 0.002). Conclusion: A greater number of intravitreal anti–vascular endothelial growth factor injections is associated with an increased risk for sustained IOP elevation in eyes with neovascular age-related macular degeneration receiving intravitreal ranbizumab and/or bevacizumab.

Gene Therapy in Patient-specific Stem Cell Lines and a Preclinical Model of Retinitis Pigmentosa With Membrane Frizzled-related Protein Defects

Defects in Membrane Frizzled-related Protein (MFRP) cause autosomal recessive retinitis pigmentosa (RP). MFRP codes for a retinal pigment epithelium (RPE)-specific membrane receptor of unknown function. In patient-specific induced pluripotent stem (iPS)-derived RPE cells, precise levels of MFRP, and its dicistronic partner CTRP5, are critical to the regulation of actin organization. Overexpression of CTRP5 in naïve human RPE cells phenocopied behavior of MFRP-deficient patient RPE (iPS-RPE) cells. AAV8 (Y733F) vector expressing human MFRP rescued the actin disorganization phenotype and restored apical microvilli in patient-specific iPS-RPE cell lines. As a result, AAV-treated MFRP mutant iPS-RPE recovered pigmentation and transepithelial resistance. The efficacy of AAV-mediated gene therapy was also evaluated in Mfrp(rd6)/Mfrp(rd6) mice--an established preclinical model of RP--and long-term improvement in visual function was observed in AAV-Mfrp-treated mice. This report is the first to indicate the successful use of human iPS-RPE cells as a recipient for gene therapy. The observed favorable response to gene therapy in both patient-specific cell lines, and the Mfrp(rd6)/Mfrp(rd6) preclinical model suggests that this form of degeneration caused by MFRP mutations is a potential target for interventional trials.

Intraocular Pressure in Patients with Neovascular Age-Related Macular Degeneration Receiving Intravitreal Aflibercept or Ranibizumab

PURPOSE To assess change in intraocular pressure (IOP) in patients with neovascular age-related macular degeneration (NVAMD) receiving intravitreal aflibercept injection (IAI) or ranibizumab in VEGF Trap-Eye: Investigation of Efficacy and Safety in Wet AMD (VIEW) 1 and 2 studies. DESIGN Analyses from 2 randomized, active-controlled, phase III trials. PARTICIPANTS A total of 2457 patients with NVAMD. METHODS Patients received IAI 2 mg every (q) 4 weeks (2q4), 0.5 mg q4 weeks (0.5q4), 2 mg q8 weeks (after 3 monthly doses; 2q8), or ranibizumab 0.5 mg q4 weeks (Rq4) for 52 weeks. At week 52, patients were switched to a variable regimen requiring at least quarterly dosing and allowing interim injections based on anatomic and visual assessment. MAIN OUTCOME MEASURES Pre-injection IOP was analyzed in study and uninjected fellow eyes from baseline to week 96. Prespecified end points included mean change in IOP from baseline and prevalence of a >21 mmHg and >10 mmHg increase in IOP from baseline. Cumulative incidence of sustained (at 2 consecutive visits) IOP >21 mmHg, a single event of IOP >25 mmHg, and sustained IOP increase from baseline (≥5 mmHg) was also evaluated. RESULTS Mean IOP change from baseline over 96 weeks in all IAI groups was consistently lower than in the Rq4 group, and this finding was replicated in both trials. In an analysis integrating both studies, the proportion of study eyes with IOP >21 mmHg at week 96 was 20.2%, 14.2%, 12.1%, and 12.5% in Rq4, 2q4, 2q8, and 0.5q4, respectively. Reduction in risk, relative to Rq4, of having sustained IOP >21 mmHg over 96 weeks was 62% (95% confidence interval [CI], 36%-78%), 50% (95% CI, 19%-70%), and 69% (95% CI, 45%-84%) for 2q4, 2q8, and 0.5q4, respectively. Risk reduction in the IAI groups for a sustained IOP increase ≥5 mmHg was 31% (95% CI, 8%-48%), 38% (95% CI, 17%-54%), and 47% (95% CI, 27%-61%), respectively. In uninjected fellow eyes, only sustained IOP >21 mmHg events were higher in the Rq4 group compared with all IAI groups. CONCLUSIONS Incidence of elevated IOP in eyes with NVAMD was lower in all IAI groups than in the ranibizumab group.

ASSOCIATION BETWEEN NEEDLE SIZE, POSTINJECTION REFLUX, AND INTRAOCULAR PRESSURE SPIKES AFTER INTRAVITREAL INJECTIONS.

Purpose: To compare the effect of 30-gauge versus 32-gauge needle size on postinjection reflux and immediate postinjection intraocular pressure (IOPimmed_post) spikes in eyes injected with anti-vascular endothelial growth factor agents. Methods: This was a prospective interventional case series of 65 eyes of 54 consecutive patients in a clinical practice setting who received intravitreal anti-vascular endothelial growth factor therapy. All eyes had preinjection IOP, IOPimmed_post, postinjection reflux, and axial lengths recorded. Results: There was a higher incidence of postinjection reflux in eyes injected with 30-gauge (53%) compared with those injected with 32-gauge (13%, P = 0.0007). Among 34 eyes injected with 30-gauge, 16 eyes without appreciable postinjection reflux had mean IOPimmed_post of 44.3 ± 7.48 mmHg and mean IOPimmed_post elevation of 29.6 ± 2.10 mmHg, which was significantly higher than the 18 eyes with reflux (mean IOPimmed_post of 18.8 ± 7.15 mmHg and mean IOPimmed_post elevation of 4.5 ± 1.74 mmHg, P < 0.0001). Among 31 eyes injected with 32-gauge, 27 eyes without appreciable postinjection reflux had mean IOPimmed_post of 44.4 ± 10.82 mmHg and mean IOPimmed_post elevation of 29.5 ± 1.99 mmHg, which was significantly higher than the 4 eyes with reflux (mean IOPimmed_post of 21.3 ± 8.54 mmHg and mean IOPimmed_post elevation of 9.5 ± 4.05 mmHg, P < 0.001). The differences in reflux and IOP between the two groups were unrelated to axial lengths (P = 0.451). Conclusion: Eyes receiving injections with 32-gauge needles had a lower incidence of postinjection reflux and higher mean IOP immediately after injection.

Influence of axial length and postinjection reflux on sustained intraocular pressure elevation as a result of intravitreal anti-vascular endothelial growth factor therapy.

Purpose: To assess an association of axial length (AL) or postinjection reflux with transient or sustained intraocular pressure (IOP) elevation in patients with neovascular age-related macular degeneration receiving anti–vascular endothelial growth factor injections. Methods: One hundred and forty-seven eyes from 74 consecutive patients with neovascular age-related macular degeneration who presented to a single physician over a 2-month period had ALs measured by IOLMaster. Twenty-one patients had preinjection and immediate postinjection IOP measured and immediate reflux assessed. Results: Overall, 9.5% of eyes had been identified with sustained IOP elevation in our previous study. Axial length did not significantly differ between eyes that had (AL, 23.96 ± 0.66 mm; n = 14) and had not experienced sustained IOP elevation (AL, 23.44 ± 1.24 mm; n = 133; P = 0.12, t-test). By linear regression analysis, the relationship between experiencing sustained IOP elevation and AL was not statistically significant (R2 = 0.0165; P = 0.121). The relationship between AL and immediate postinjection IOP elevation was also not statistically significant (R2 = 0.0001; P = 0.97). Immediate postinjection IOP increase did differ between eyes without reflux (30.2 ± 9.3 mmHg; n = 12) and those with reflux (1.1 ± 7.2; n = 9; P < 0.001). Conclusion: Axial length does not seem to be a predictor of transient or sustained IOP elevation. Repeated trabecular meshwork trauma related to the absence or presence of reflux and immediate postinjection IOP elevation may be a contributing factor.

The "pitchfork sign" a distinctive optical coherence tomography finding in inflammatory choroidal neovascularization.

Purpose: To report four examples of a novel optical coherence tomography finding, which appears to be characteristic of inflammatory choroidal neovascularization. Methods: Retrospective observational case series. Results: Four eyes of four patients were diagnosed clinically with inflammatory choroidal neovascularization and underwent optical coherence tomography. In each case, imaging revealed multiple, distinctive finger-like projections extending from the area of active choroidal neovascularization into the outer retina—the “pitchfork sign”—a finding not typically seen in Type 2 neovascularization due to other etiologies. Conclusion: The pitchfork sign may help distinguish inflammatory choroidal neovascularization from other causes of Type 2 neovascularization.

Long-term follow-up of acute zonal occult outer retinopathy.

Background: Acute zonal occult outer retinopathy (AZOOR) was described by Gass in 1992 as an independent posterior uveitis characterized by photopsias and rapid visual field zonal loss, with 70% of cases stabilizing within 6 months, although there is a paucity of long-term documentation of AZOOR cases. Methods: The authors reported the case of a 55-year-old woman diagnosed with AZOOR and followed for 13 years. Results: Best-corrected visual acuity at baseline was 20/60 in her right eye and 20/25 in her left eye, with an annular peripapillary area of irregular retinal thickening and temporal visual field loss in both eyes. Over her 13-year follow-up, best-corrected visual acuity dropped to 20/60 in both eyes and visual field loss because of chorioretinal atrophy progressed significantly. Antiviral and immunomodulatory drugs did not halt this progression. Conclusion: The prognosis of cases with AZOOR should be cautiously considered. The authors showed that in the long term, chorioretinal atrophy may lead to severe visual field loss in patients with AZOOR.

Late recurrence of myopic foveoschisis after successful repair with primary vitrectomy and incomplete membrane peeling.

Purpose: To report three cases of late recurrence of myopic foveoschisis (MF) after initial successful repair with pars plana vitrectomy and membrane peeling to assess the importance of internal limiting membrane peeling. Methods: A retrospective noncomparative case series was performed of patients who underwent a primary pars plana vitrectomy by a single surgeon with successful resolution of MF, but eventually underwent repeat pars plana vitrectomy for recurrent MF. Best-corrected visual acuity, fundus photography, and optical coherence tomography were obtained at each examination. Results: Three eyes of three patients underwent pars plana vitrectomy for recurrent MF. Myopic foveoschisis recurrence occurred 6, 3.5, and 12 years after the primary vitrectomy, respectively. Repeat vitrectomy with staining and additional peeling of the internal limiting membrane resulted in good anatomical outcome and stabilization of visual acuity in all cases. Conclusion: Late recurrence of MF after successful primary vitrectomy is described. Fibrocellular proliferation on residual cortical vitreous or incomplete internal limiting membrane peeling during the initial vitrectomy may underlie recurrence.

LONG-TERM RETROSPECTIVE ANALYSIS OF VISUAL ACUITY AND OPTICAL COHERENCE TOPOGRAPHIC CHANGES AFTER SINGLE VERSUS DOUBLE PEELING DURING VITRECTOMY FOR MACULAR EPIRETINAL MEMBRANES.

Purpose: To determine the long-term effect of internal limiting membrane with associated epiretinal membrane (ERM) peeling versus single peeling alone in terms of best-corrected visual acuity and anatomical outcomes on spectral-domain optical coherence tomography. Methods: This retrospective comparative cohort study of patients who had follow-up of >1 year and underwent surgery for ERM by a single surgeon (S.C.) from January 1, 2008 to December 31, 2012 compared cases in which the internal limiting membrane was stained with brilliant blue G to facilitate double peeling (n = 42) and single peeling (n = 43) of the ERM alone for up to 3 years of follow-up. For continuous variables, an independent two-tailed t-test was performed. For binary variables, the Fishers exact test was performed. Statistical significance was defined as P < 0.05. Results: Eighty-five of 142 patients fit the inclusion criteria. At the last follow-up, the single-peeling group were more likely to have ERM remaining in the central fovea postoperatively (P = 0.0020, becoming significant by postoperative Year 1, P = 0.022) and less likely to develop inner retinal dimpling (P = 0.000, becoming significant by postoperative Month 3, P = 0.015). At 3 years, central foveal thickness had decreased in the single-peeling group by −136.9 µm and by −84.1 &mgr;m in the double-peeling group, which was not significantly different (P = 0.08). Mean best-corrected visual acuity improved in both the groups at all time points. There was no statistically significant difference between the 2 groups at 3 years (P = 0.44; single-peeling group, 0.32 ± 0.42, Snellen 20/42; double-peeling group, 0.23 ± 0.27, Snellen 20/34). Conclusion: Brilliant blue G–assisted internal limiting membrane peeling for ERM results in a more thorough removal of residual ERM around the paracentral fovea. However, there is no difference in long-term best-corrected visual acuity at 3 years and a greater likelihood of inner retinal dimpling.