Optical coherence tomography angiography patterns of type 1 macular neovascularization in age-related macular degeneration patients.

PURPOSE: To compare morphologic characteristics of type 1 macular neovascularization (MNV) flow pattern in treatment-naïve and previously treated patients with age-related macular degeneration (AMD) as assessed by optical coherence tomography angiography (OCTA). STUDY DESIGN: Cross-sectional study. MATERIALS AND METHODS: Macular OCT angiography images were acquired using RTVue XR Avanti with AngioVue. Distinct morphologic biomarkers and quantifiable features of the neovascular membranes were studied on en-face projection images comparing treatment-naïve and previously treated patients. RESULTS: The study included 68 eyes of 58 patients. Among them, 24 eyes were treatment-naïve, and the remaining eyes had received a mean of 19.6 injections. Immature lesions were more associated with treatment-naïve eyes and hyper-mature lesions were associated with previously treated eyes (p = 0.005). Tangle pattern was associated with treatment-naïve eyes (p = 0.013), whereas mature core vessels and sea fan pattern were associated more with previously treated eyes (p = 0.001 and p = 0.044, respectively). Vascular density of the neovascular membrane was higher in the treatment-naïve group (p = 0.036) and the average MNV area was similar between the 2 groups (p = 0.683). CONCLUSIONS: Based on OCTA, morphologic biomarkers of type 1 MNV might be an indication of previous treatment. The MNV pattern can improve our understanding of its maturation under anti-VEGF treatment and might be valuable to better guide therapeutic decisions and provide more personalized care to patients with AMD.

Factors associated with extended remission in neovascular age-related macular degeneration on pro re nata treatment protocol.

AIM: To show the characteristics and outcomes of patients with neovascular age-related macular degeneration (nAMD) who had extended remission (ER) while on a pro re nata (PRN) treatment protocol. METHODS: This was a retrospective case-control study of a consecutive series of patients with nAMD treated with a PRN antivascular endothelial growth factor (anti-VEGF) drug regimen. ER was defined as the absence of haemorrhage, intraretinal/subretinal fluid on optical coherence tomography and leakage on fluorescein angiography for 52 weeks after cessation of anti-VEGF therapy. Matching patients with nAMD who did not achieve ER were included as control group. Cox regression analysis was fitted to identify predictors of time to achieve ER and time to recurrence. A logistic regression analysis of baseline characteristics was used to identify predictors of achieving ER. RESULTS: Of 830 eyes treated with anti-VEGF monotherapy, 77 (9.2%) eyes achieved ER during a median follow-up of 236 weeks (range 70-525 weeks). Cox regression analysis showed that ER was achieved earlier in eyes with isolated intraretinal fluid (HR, 2.05; 95% CI 1.929 to 4.520; p=0.045) at presentation. Logistic regression analysis showed that type 3 choroidal neovascularisation (OR, 0.090; 95% CI 0.021 to 0.382; p=0.001), thinner choroid (OR, 0.993; 95% CI 0.988 to 0.998; p=0.004) and absence of macular atrophy (OR, 0.233; 95% CI 0.065 to 0.839; p=0.026) at baseline increased the likelihood of achieving ER. CONCLUSION: ER is achievable in 9.2% of patients under PRN therapy for nAMD. At presentation with nAMD, anatomical features on retinal imaging may predict the likelihood of achieving ER and a shorter time to achieve ER.

Foveal Avascular Zone Distortion in Epiretinal Membrane by Optical Coherence Tomography Angiography.

BACKGROUND AND OBJECTIVE: To show the morphologic changes on the foveal avascular zone (FAZ) in patients with epiretinal membrane (ERM) using optical coherence tomography angiography (OCTA) and to demonstrate the correlation between distortion of FAZ and features of the ERM. PATIENTS AND METHODS: FAZ eccentricity index (longest diameter of FAZ/shortest diameter of FAZ) was measured in 52 patients with ERM and compared with 27 healthy subjects' values. The density of the ERM was quantified using a grading scale (0-3) on multicolor scanning laser images, and spectral-domain OCT characteristics of the eyes were assessed. RESULTS: Of the 52 eyes with ERM, 31 eyes (59.61%) showed some foveal remodeling, including full (13.46%) or partial (30.76%) apparent vascularization of FAZ, presence of a vessel crossing the fovea (9.61%), and horizontal or vertical elongation of FAZ (5.76%). The mean FAZ eccentricity index was 0.84 ± 0.46 (range: 0.0-1.86) in eyes with ERM and 0.98 ± 0.07 (range: 0.96-1.02) in the control subjects, respectively (P = .02). There was a negative significant correlation between FAZ eccentricity index and central macular thickness (P = .04). CONCLUSIONS: Thickening of the central fovea leads to foveal remodeling in ERM eyes, and OCTA enables the visualization of architectural FAZ changes. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:295-301.].

Durability of every-8-week aflibercept maintenance therapy in treatment-experienced neovascular age-related macular degeneration.

PURPOSE: To determine the proportion of treatment-experienced eyes with exudative age-related macular degeneration successfully treated with every-4-week aflibercept that can be kept dry on fixed every-8-week aflibercept injections (maintenance). METHODS: In this retrospective chart review, we evaluated our cohort of patients treated with a treatment paradigm for CNV in AMD. Initially, patients were treated with bevacizumab or ranibizumab and switched to every-4-week aflibercept when therapeutic responses were not durable or were suboptimal. Maintenance every-8-week therapy was initiated when the retina was completely dry on every-4-week aflibercept therapy. The primary outcome measure was recurrence of exudation on optical coherence tomography (OCT) during maintenance. RESULTS: Thirty-six eyes of 31 consecutive patients with median age of 79 years (range, 65-89) were included. Maintenance was started after a median of 34 (range, 8-88) injections. Recurrence was observed in 20 eyes (55%). Of these, 11 eyes (31%) reactivated at 8 weeks. Median time to failure of maintenance schedule was 40 weeks by Kaplan-Meier analysis. Baseline demographic and anatomic characteristics were not associated with failure of maintenance schedule. CONCLUSION: In treatment-experienced eyes that respond completely to every-4-week aflibercept, maintenance therapy with every-8-week injections can only temporarily maintain anatomic success with the majority of eyes developing recurring activity. This regimen fails early in one third of eyes and has a median effective duration of 40 weeks. Aflibercept appears to be inadequate to maintain control of exudation in most eyes in at least half of eyes undergoing long-term therapy.

AGE-RELATED MACULAR DEGENERATION-ASSOCIATED PERIPAPILLARY CHOROIDAL NEOVASCULARIZATION IN THE ERA OF ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY.

PURPOSE: To characterize the natural history and response of age-related macular degeneration-associated peripapillary choroidal neovascularization to anti-vascular endothelial growth factor therapy. METHODS: This was a retrospective case series of patients with peripapillary choroidal neovascularization secondary to neovascular age-related macular degeneration. All patients underwent complete ophthalmologic examination and retinal imaging including fluorescein angiography and spectral domain optical coherence tomography at each visit. Eyes with subretinal or intraretinal macular fluid were treated with anti-vascular endothelial growth factor monotherapy using a modified as-needed treatment algorithm. RESULTS: Thirty-three eyes of 27 patients were included. The median age was 82 years (range, 62-94), and the median duration of follow-up was 65 months (range, 6-165). Fourteen eyes (58%) without fovea-involving fluid at baseline subsequently developed exudation after a median observation period of 16 months (range, 4-107). Ten of 24 eyes (42%) without initial macular fluid remained dry during the entire follow-up. The median number of injections required until complete fluid reabsorption was 3 (range, 1-21) during the first treatment cycle. The median time to fluid recurrence was 6 months (range, 3-74). CONCLUSION: Peripapillary choroidal neovascularization secondary to wet age-related macular degeneration has a slow progression, may not require treatment for a prolonged period, and responds rapidly to anti-vascular endothelial growth factor treatment with good visual outcomes.

Correlates of Good Vision in Eyes With Subfoveal Scars From Neovascular Age-Related Macular Degeneration.

BACKGROUND AND OBJECTIVE: To compare subfoveal disciform scars with good and poor vision in patients with neovascular age-related macular degeneration (nAMD). PATIENTS AND METHODS: A retrospective case-control study. Twenty-two eyes of 21 consecutively treated patients with nAMD with subfoveal disciform scar and best-corrected visual acuity (BCVA) of 20/63 or better at the final visit were included. Twenty-one eyes of 21 matched patients with disciform scar and final BCVA less than 20/63 served as controls. RESULTS: Subretinal pigment epithelium scar location was more common in the good vision group than in the poor vision group (P < .001). The mean percent disruption of the ellipsoid and the external limiting membrane layers was significantly greater in poor vision eyes than in good vision eyes from scar formation and throughout follow-up (all P < .01). CONCLUSION: Preserved photoreceptor layer correlated with good vision in patients with nAMD and subfoveal disciform scar. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:765-774.].

Bevacizumab dosing every 2 weeks for neovascular age-related macular degeneration refractory to monthly dosing.

PURPOSE: To evaluate intravitreal bevacizumab every 2 weeks (biweekly) in refractory neovascular age-related macular degeneration (nAMD). STUDY DESIGN: Retrospective study. METHODS: A retrospective study of consecutive nAMD patients unresponsive to monthly intravitreal anti-vascular endothelial growth factor (VEGF) switched to 3-4 biweekly injections. RESULTS: Twenty-seven eyes of patients aged 82.08 ± 6.85 years were included. Prior to the 2-week interval bevacizumab injections, 74.1% (n=20) were treated with both bevacizumab and ranibizumab, 11.1% (3 eyes) also received aflibercept and 14.8% (4 eyes) had received prior treatment of monthly bevacizumab (average number of injections 21.5 ± 6.7). Best corrected visual acuity (BCVA) remained stable between baseline (logMAR 0.72± 0.60) and follow-up (0.76± 0.66) (p=0.41). Mean central macular thickness and macular volume did not change significantly between baseline and follow-up (p=0.35 and p=0.60, respectively). Six eyes (22.2%) showed morphologic anatomic improvements, while 19 eyes (70.4%) were stable and two eyes (7.4%) deteriorated from baseline. Subretinal fluid completely resolved in 3 of the eyes and improved in the other 3 eyes and in this group (22.2%) both central macular thickness (326.2 ± 101.4 versus 297.5 ± 97.2, p=0.002) and macular volume (8.69 ± 1.69 versus 8.22 ± 1.43, p=0.03) were significantly reduced. No adverse events were observed in any of the treated eyes. CONCLUSION: This study demonstrates that biweekly bevacizumab injections are effective in nearly one-quarter of nAMD non-responders with no adverse events reported. Switching earlier, rather than later, to this low cost modality may be of benefit for a portion of non-responders to conventional treatment.

Comparison of conventional color fundus photography and multicolor imaging in choroidal or retinal lesions.

PURPOSE: Our purpose was to compare the characteristics of the retinal and choroidal lesions including choroidal nevus, choroidal melanoma and congenital hypertrophy of the retina pigment epithelium using conventional color fundus photography (CFP) and multicolor imaging (MCI). METHODS: The paired images of patients with retinal or choroidal lesions were assessed for the visibility of lesion's border, halo and drusen using a grading scale (0-2). The area of the lesion was measured on both imaging modalities. The same grading was also done on the individual color channels of MCI for a further evaluation. RESULTS: Thirty-three eyes of 33 patients were included. There were no significant differences in the mean border, drusen and halo visibility scores between the two imaging modalities (p = 0.12, p = 0.70, p = 0.35). However, the mean area of the lesion was significantly smaller on MCI than that on CFP (14.9±3.3 versus 18.7±3.4 mm2, p = 0.01). CONCLUSION: The appearance of choroidal and/ or retinal lesions on MCI may be different than that on CFP. Though MCI can provide similar information with CFP for the features of retinal and/ or choroidal lesions including border, halo and drusen; the infrared light reflection on MCI underestimates the extent of the choroidal lesion by 33%.

LONG-TERM REMISSION OF NEOVASCULAR AGE-RELATED MACULAR DEGENERATION WITH AS-NEEDED ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY.

PURPOSE: To determine the presenting characteristics of patients with neovascular age-related macular degeneration with long-term remission (LTR), which was defined as the absence of intraretinal/subretinal fluid, or hemorrhage, and absence of leakage on fluorescein angiography for longer than 6 months while on as-needed antivascular endothelial growth factor treatment. METHODS: The presenting characteristics of patients with LTR were compared with a control group including 32 eyes of 28 age-, gender-, and ethnicity-matched patients who did not achieve LTR. RESULTS: Seventy-four percent of patients in the LTR group had Type 1 choroidal neovascular membrane and 18.5% had retinal angiomatous proliferation. In the control group, 28 eyes had Type 1 choroidal neovascular membrane (87.5%), and none of the patients had retinal angiomatous proliferation; overall, there was a significant difference in lesion types between the 2 groups (P = 0.036). Eyes with LTR at presentation had significantly thinner subfoveal choroidal thickness (147 vs. 178 µm, P = 0.04). There was more intraretinal fluid and less subretinal fluid at the presentation in the remission group (59.3% intraretinal fluid and 11.1% subretinal fluid) compared with the control group (28.1% intraretinal fluid and 34.4% subretinal fluid, P = 0.03). CONCLUSION: The presence of retinal angiomatous proliferation, thinner choroidal thickness, more intraretinal fluid, and less subretinal fluid at presentation were associated with LTR in patients receiving as-needed treatment for age-related macular degeneration.

HIGH-DOSE HIGH-FREQUENCY AFLIBERCEPT FOR RECALCITRANT NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To determine the efficacy of monthly (0.1 mL/4 mg) aflibercept for refractory neovascular age-related macular degeneration (wet age-related macular degeneration). METHODS: This was a retrospective interventional case series in which patients with wet age-related macular degeneration were treated with stepwise dose escalation. Nonvitrectomized patients resistant to monthly (Q4W) ranibizumab/bevacizumab were switched to 2 mg aflibercept every 8 weeks. With resistance, they were escalated to Q4W 2 mg aflibercept, then Q4W 4 mg (high dose high frequency, 4Q4W) aflibercept. Resistance was defined as ≥2 recurrences after being dry following ≥3 injections or persistent exudation on treatment of ≥5 injections. RESULTS: Thirty-three eyes of 28 patients were treated with 4Q4W aflibercept and followed for a mean of 16 months. A dry retina (no intraretinal or subretinal fluid) was achieved after initiating 4Q4W aflibercept treatment at a mean of 3.8 months. Central foveal thickness, maximum foveal thickness, intraretinal fluid, subretinal fluid, and retinal pigment detachment height decreased significantly at 1 month after initiating the 4Q4W aflibercept, and the morphologic therapeutic effect was sustained until the last visit. Forty-five percent of eyes had one or more lines of vision improvement. New geographic atrophy developed in 9% of eyes during follow-up. No ocular or systemic adverse events occurred after initiating 4Q4W aflibercept. CONCLUSION: Intravitreal high-dose high-frequency aflibercept is an effective treatment for patients with refractory wet age-related macular degeneration.

Intravitreal Administration of Antiviral Agents in Silicone Oil-Filled Human Eyes.

PURPOSE: To report our experience with intra-silicone oil (SO) injection of antiviral agents for treatment of viral retinitis and to review the relevant literature. DESIGN: Two case reports and a literature review. PARTICIPANTS: Two patients with viral retinitis and SO tamponade. METHODS: Two patients with viral retinitis were treated with intravitreal injections of low-dose ganciclovir (2 mg/0.05 ml), foscarnet (1.2 mg/0.05 ml), or both after retinal detachment repair with SO tamponade, in addition to systemic antiviral therapy from 2014 through 2015. The literature on the use of intraocular antiviral agents in the setting of SO vitreous substitute was reviewed. MAIN OUTCOME MEASURES: Clinical outcomes after administration of intra-SO antiviral therapy. RESULTS: A patient with progressive outer retinal necrosis received 5 intra-SO injections of low-dose ganciclovir and foscarnet after surgery over 6 weeks. Another patient with acute retinal necrosis received weekly low-dose foscarnet injections into his SO-filled eye for 8 weeks after surgery. Significant retinitis regression with long-term retinitis control was achieved in both patients throughout follow-up. No articles reporting the administration of soluble antiviral agents into an SO-filled human eye were identified. CONCLUSIONS: Our preliminary findings indicate that administration of low-dose ganciclovir and foscarnet into an SO-filled eye may be used as adjunctive treatment for viral retinitis. Further studies are needed to confirm these results.

High-frequency aflibercept injections in persistent neovascular age-related macular degeneration.

PURPOSE: To report the 1-year outcomes of every-4-weeks (Q4W) as-needed aflibercept treatment in resistant neovascular age-related macular degeneration (nAMD) patients who had been treated and failed prior bevacizumab or ranibizumab injections, and who also responded poorly to every-8-weeks (Q8W) aflibercept treatment. METHODS: Forty-three eyes of 39 patients with persistent nAMD despite monthly bevacizumab and/or ranibizumab injections and who were switched to Q8W 2-mg aflibercept injections, but showed persistence of fluid were included. Patients were treated with as-needed Q4W aflibercept injections with monthly monitoring. Maximum retinal thickness (MRT), central macular thickness (CMT), maximum pigment epithelial detachment height (PED) and best-corrected visual acuity (BCVA) were assessed and compared to baseline when high-frequency aflibercept was initiated. RESULTS: A mean of 8 (interquartile range, 4-11) Q4W injections were given during the follow-up. MRT and CMT significantly decreased at all follow-up visits (p < 0.05); however, there was no significant change in maximum PED height (p > 0.05) at any visit. Mean BCVA was 0.38 ± 0.28 (logMAR) (≈20/63, Snellen) at baseline, and 0.4 ± 0.34 (logMAR) (≈20/76, Snellen) at 1 year (p = 0.76). Seventy-two percent of eyes maintained a final BCVA of 20/63 or better. Twelve eyes (28 %) had some subretinal scar tissue formation and 5 eyes (11.6 %) had evidence of atrophy at 1 year. CONCLUSION: A stepwise algorithm with Q4W as-needed aflibercept treatment led to anatomic improvement in previously treated eyes which failed other therapies, including aflibercept every 8 weeks. Lack of visual improvement may be due to a ceiling effect as our eyes generally had good visual acuity.