Jesse J. Jung

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.

Type 3 neovascularization: evolution, association with pigment epithelial detachment, and treatment response as revealed by spectral domain optical coherence tomography.

Purpose: To demonstrate the evolution and treatment response of Type 3 neovascularization using spectral domain optical coherence tomography. Methods: We retrospectively analyzed 40 eyes treated with intravitreal anti-vascular endothelial growth factor therapy for Type 3 neovascularization over a variable follow-up period. Results: In 17 eyes, spectral domain optical coherence tomography captured the development of Type 3 neovascularization from punctate hyperreflective foci that preceded any outer retinal defect. The more mature Type 3 lesions were associated with outer retinal disruption and adjacent cystoid macular edema. In addition, 37 of 40 Type 3 lesions (93%) were associated with an underlying pigment epithelial detachment, of which 26 (70%) were drusenoid, 6 (16%) serous, and 5 (14%) mixed. Type 3 vessels appeared to leak fluid into the pigment epithelial detachment cavity, creating serous pigment epithelial detachments as large as 925 &mgr;m in maximal height. Treatment with anti-vascular endothelial growth factor agents led to prompt involution of the lesion and resorption of the intraretinal and subretinal pigment epithelium fluid after one or two injections (median = 1). Conclusion: In some eyes with age-related macular degeneration, the earliest sign of Type 3 neovascularization is punctate hyperreflective foci above the external limiting membrane. The mature Type 3 lesions and associated serous pigment epithelial detachments are highly responsive to anti-vascular endothelial growth factor therapy.

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.

CENTRAL SEROUS CHORIORETINOPATHY TREATED WITH MINERALOCORTICOID ANTAGONISTS: A ONE-YEAR PILOT STUDY.

Purpose: To assess the treatment response to mineralocorticoid antagonists in a pilot study of patients diagnosed with central serous chorioretinopathy using multimodal imaging. Methods: This retrospective observational case series included 23 eyes of 14 patients with central serous chorioretinopathy treated by a single physician (L.A.Y.) with either spironolactone, eplerenone, or both consecutively over a 12-month period. Choroidal thickness, central macular thickness, and best-corrected visual acuity were measured and compared with baseline values. Twelve eyes of 11 patients demonstrated subretinal fluid before or during the initiated treatment course. Subretinal fluid was measured and compared with baseline values in this subgroup. Results: In all eyes (n = 23), best-corrected visual acuity improved at 12 months of treatment; however, central macular thickness and choroidal thickness showed no improvement. In the subgroup with subretinal fluid (n = 12), subretinal fluid was significantly decreased at 6 months and 12 months of treatment; however, central macular thickness, choroidal thickness, and best-corrected visual acuity showed no significant change. Conclusion: Mineralocorticoid antagonists may improve best-corrected visual acuity and decrease subretinal fluid in patients with central serous chorioretinopathy, but do not affect the choroidal or macular thickness. This pilot study demonstrates that mineralocorticoid receptor antagonists may be effective in treating central serous chorioretinopathy but warrants consideration for future research within a randomized clinical trial.

A Comparison Between Optical Coherence Tomography Angiography and Fluorescein Angiography for the Imaging of Type 1 Neovascularization

PURPOSE To determine the sensitivity of the combination of optical coherence tomography angiography (OCTA) and structural optical coherence tomography (OCT) for detecting type 1 neovascularization (NV) and to determine significant factors that preclude visualization of type 1 NV using OCTA. METHODS Multicenter, retrospective cohort study of 115 eyes from 100 patients with type 1 NV. A retrospective review of fluorescein (FA), OCT, and OCTA imaging was performed on a consecutive series of eyes with type 1 NV from five institutions. Unmasked graders utilized FA and structural OCT data to determine the diagnosis of type 1 NV. Masked graders evaluated FA data alone, en face OCTA data alone and combined en face OCTA and structural OCT data to determine the presence of type 1 NV. Sensitivity analyses were performed using combined FA and OCT data as the reference standard. RESULTS A total of 105 eyes were diagnosed with type 1 NV using the reference. Of these, 90 (85.7%) could be detected using en face OCTA and structural OCT. The sensitivities of FA data alone and en face OCTA data alone for visualizing type 1 NV were the same (66.7%). Significant factors that precluded visualization of NV using en face OCTA included the height of pigment epithelial detachment, low signal strength, and treatment-naïve disease (P < 0.05, respectively). CONCLUSIONS En face OCTA and structural OCT showed better detection of type 1 NV than either FA alone or en face OCTA alone. Combining en face OCTA and structural OCT information may therefore be a useful way to noninvasively diagnose and monitor the treatment of type 1 NV.

Associations Between Retinal Pigment Epithelium and Drusen Volume Changes During the Lifecycle of Large Drusenoid Pigment Epithelial Detachments

Purpose Drusenoid pigment epithelial detachments (PEDs) are a defined path to atrophy in age-related macular degeneration (AMD). We analyzed the relationships between retinal pigment epithelium (RPE) and drusen volume changes during the PED lifecycle, using spectral-domain optical coherence tomography (SD-OCT). Methods Twenty-one cases of drusenoid PED tracked using SD-OCT through periods of growth and collapse were evaluated. Volumetric calculations and piece-wise linear regression analysis were used to determine the breakpoint between growth and collapse. Spectral-domain OCT scans were independently evaluated for the appearance of intraretinal hyperreflective foci, acquired vitelliform lesions (AVLs), and disruptions to the RPE+basal lamina band. Timing of these events with respect to the breakpoint was statistically evaluated. Morphometric characteristics of drusenoid PEDs were correlated with rate of PED collapse and final visual acuity. Results Mean age of subjects was 75.3 years and mean period of follow up was 4.1 years (median 4.5 years; range, 0.6–6.6 years). The lifecycle of drusenoid PEDs was asymmetric, in that the rate of collapse (0.199 mm3/month) is significantly faster (P < 0.001) than the rate of growth (0.022 mm3/month). Appearance of intraretinal hyperreflective foci and AVLs preceded the breakpoint (both P < 0.001). The timing of disruptions to the RPE+basal lamina band did not differ from the breakpoint (P = 0.510). Maximal height, volume, and diameter of drusenoid PEDs were inversely correlated with final visual acuity (all P < 0.001) and positively correlated with the rate of PED collapse (all P < 0.001). Conclusions Spectral-domain OCT signatures, plausibly attributable to anteriorly migrated RPE and disintegration of the RPE layer, precede or occur simultaneously with changes in volume of drusenoid PED during the lifecycle of this lesion.

Long-Term Visual Outcomes for a Treat and Extend Anti-Vascular Endothelial Growth Factor Regimen in Eyes with Neovascular Age-Related Macular Degeneration

With the advent of anti-vascular endothelial growth factor (VEGF) therapy, clinicians are now focused on various treatment strategies to better control neovascular age-related macular degeneration (NVAMD), a leading cause of irreversible blindness. Herein, we retrospectively reviewed consecutive patients with treatment-naïve NVAMD initially classified based on fluorescein angiography (FA) alone or with an anatomic classification utilizing both FA and optical coherence tomography (OCT) and correlated long-term visual outcomes of these patients treated with an anti-VEGF Treat-and-Extend Regimen (TER) with baseline characteristics including neovascular phenotype. Overall, 185 patients (210 eyes) were followed over an average of 3.5 years (range 1–6.6) with a retention rate of 62.9%, and visual acuity significantly improved with a TER that required a mean number of 8.3 (±1.6) (± standard deviation) intravitreal anti-VEGF injections/year (range 4–13). The number of injections and the anatomic classification were independent predictors of visual acuity at 6 months, 1, 2, 3 and 4 years. Patients with Type 1 neovascularization had better visual outcomes and received more injections than the other neovascular subtypes. There were no serious adverse events. A TER provided sustained long-term visual gains. Eyes with Type 1 neovascularization had better visual outcomes than those with other neovascular subtypes.

Long-term Follow-up of Outer Retinal Tubulation Documented by Eye-Tracked and En Face Spectral-Domain Optical Coherence Tomography

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Correlation between neovascular lesion type and clinical characteristics of nonneovascular fellow eyes in patients with unilateral, neovascular age-related macular degeneration.

Purpose: To investigate the association between the type of neovascularization (NV) and the clinical characteristics of nonneovascular fellow eyes in patients with unilateral, neovascular age-related macular degeneration. Methods: Eighty-three patients with treatment-naive, unilateral, neovascular age-related macular degeneration were retrospectively analyzed. Neovascular lesions were classified using both fluorescein angiography and optical coherence tomography as Type 1 (subretinal pigment epithelium), 2 (subretinal), 3 (intraretinal), or mixed NV. The associations between NV lesion type and baseline clinical and imaging characteristics of the fellow eye, including central geographic atrophy, noncentral geographic atrophy, pigmentary changes, soft drusen, cuticular drusen, reticular pseudodrusen, and subfoveal choroidal thickness, were examined. Subfoveal choroidal thickness was defined as thin if thickness was <120 &mgr;m. Results: In the fellow eyes of patients with treatment-naive, unilateral, neovascular age-related macular degeneration, Type 3 NV had an increased adjusted odds ratio of reticular pseudodrusen (15.361, P < 0.001) and thin subfoveal choroidal thickness (21.537, P < 0.001) as well as a tendency toward an increased adjusted odds ratio of central geographic atrophy (4.775, P = 0.028). Fellow eyes of patients with Type 1 NV showed a decreased adjusted odds ratio of reticular pseudodrusen (0.233, P = 0.007) and thin subfoveal choroidal thickness (0.080, P = 0.005). Conclusion: In patients with unilateral, neovascular age-related macular degeneration, certain nonneovascular features of the fellow eye correlate with the NV lesion composition based on type, as anatomically classified utilizing both fluorescein angiography and optical coherence tomography. Patients with Type 3 NV were more likely to have reticular pseudodrusen and/or thin subfoveal choroidal thickness in the fellow eye compared with those with Type 1 NV. Patients with Type 3 NV also showed a trend toward increased central geographic atrophy in the fellow eye.

Baseline Predictors for Good Versus Poor Visual Outcomes in the Treatment of Neovascular Age-Related Macular Degeneration With Intravitreal Anti-VEGF Therapy.

PURPOSE To examine the baseline factors associated with good (20/60 or better) versus poor (20/200 or worse) visual outcomes in eyes with treatment-naïve neovascular age-related macular degeneration (AMD) receiving intravitreal antivascular endothelial growth factor (VEGF) on a treat-and-extend regimen (TER). METHODS An observational, retrospective series of patients managed with a TER, identified as having either good or poor visual outcomes, was examined. A multivariate regression analysis of baseline characteristics identified factors associated with good and poor vision at 2, 3, and 4 years. Neovascular subtypes were identified using fluorescein angiography (FA) alone and the anatomic classification system with FA and optical coherence tomography (OCT). RESULTS One hundred thirty-eight patients (154 eyes) fit the inclusion criteria at 2 years, 106 patients (113 eyes) at 3 years, and 72 patients (74 eyes) at 4 years. In the multivariate analysis, type 1 lesions, according to anatomic classification, had better vision at 24 months (95% CI: [3.1, 82.7], P = 0.01), 36 months (95% CI: [1.97, 24.17], P = 0.003), and 48 months (95% CI: [2.01, 65.47], P = 0.006). Clopidogrel use was associated with poor vision at 24 months (95% CI: [0.03, 0.68], P = 0.013). Vision at 3 months was the best predictor of vision at year 4 (β = -4.277, P = 0.002). CONCLUSIONS Eyes with neovascular AMD managed with a TER of anti-VEGF therapy having type 1 neovascularization at baseline were more likely to maintain good vision over 4 years, whereas clopidogrel use predicted poor vision at 2 years. Vision at 3 months was the best predictor for favorable long-term vision.