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 Macular Staphyloma Area on Ultra-widefield Fundus Images.

PURPOSE: To assess the feasibility of applying ultra-widefield fundus (UWF) images for macular staphyloma area (MSA) measurement and investigate the associated factors with MSA. METHODS: This is a retrospective study. MSA was measured by UWF imaging. Central foveal thickness, subfoveal choroidal thickness, subfoveal scleral thickness were measured on spectral domain optical coherence tomography. Intraclass correlation coefficients of MSA measurement would be evaluated. Multiple linear regression analysis was used to analyze the associated factors with MSA. RESULTS: In total, 135 eyes of 92 patients were enrolled. The mean age was 64.73 ± 10.84 years. Mean MSA on UWF image was 279.67 ± 71.70 mm2. Intraclass correlation coefficients of MSA measurement was 0.965 (95% confidence interval [CI], 0.946 to 0.977; p < 0.001). In the multiple linear regression analysis, after adjusting for subfoveal choroidal thickness, best-corrected visual acuity, central foveal thickness, and subfoveal scleral thickness, the factors independently related to MSA were axial length (ß = 8.352; 95% CI, 3.306 to 13.398; p = 0.001), sex (ß = -26.673; 95% CI, -51.759 to -1.586; p = 0.037), age (ß = 1.184; 95% CI, 0.020 to 2.348; p = 0.046). CONCLUSIONS: It is feasible to measure MSA on UWF image. Female, longer axial length, and older age may indicate larger MSA.

ACQUIRED VITELLIFORM LESIONS: A Novel Finding in Eyes with Peripapillary Pachychoroid Syndrome.

PURPOSE: To describe a novel finding of acquired vitelliform lesions in eyes with peripapillary pachychoroid syndrome. METHODS: A retrospective, multicenter, observational case series including seven patients with peripapillary pachychoroid syndrome and concomitant acquired vitelliform lesions. Medical records and multimodal imaging findings were comprehensively reviewed. RESULTS: Six of seven patients were men, with a mean age of 72.6 years. Mean baseline best-corrected visual acuity was 0.11 ± 0.07 (Snellen equivalent 20/25), and all patients presented with baseline best-corrected visual acuity of 20/30 or better. Mean follow-up time was 24.4 months (range 1-54 months). At last follow-up, best-corrected visual acuity was stable in 13/14 eyes, and deteriorated in one eye because of subfoveal atrophy.Fundus examination revealed peripapillary retinal pigment epithelium alterations and pigment migration in all eyes. Fundus autofluorescence showed mottled hyperautofluorescence and hypoautofluorescence in the peripapillary region, and hypoautofluorescent lesions corresponding to the pigmentary changes. Optical coherence tomography showed nasal choroidal thickening and pachyvessels with overlying retinal pigment epithelium irregularity. All eyes presented with peripapillary intraretinal fluid. Subretinal fluid was present in five eyes of three patients. Acquired vitelliform lesions were present in 11 eyes. CONCLUSION: The novel association between peripapillary pachychoroid syndrome and acquired vitelliform lesions is characterized by the classic findings of both entities, and visual prognosis is accordingly good.

Quantifying the Separation Between the Retinal Pigment Epithelium and Bruch's Membrane using Optical Coherence Tomography in Patients with Inherited Macular Degeneration.

Purpose: To describe and quantify Bruch's membrane (BM) and retinal pigment epithelium (RPE) separation using spectral-domain (SD) optical coherence tomography (OCT) in patients affected by inherited macular degenerations associated with BM thickening. Methods: Patients with molecularly confirmed Sorsby fundus dystrophy (SFD), dominant drusen (DD), and late-onset retinal degeneration (L-ORD) were included in this retrospective study. Each disease was classed as early stage if subjects were asymptomatic, intermediate stage if they had nyctalopia alone, and late stage if they described loss of central vision. The main outcome was measurement of BM-RPE separation on SD-OCT. The BM-RPE separation measurements were compared against those in normal age-matched controls. Results: Seventeen patients with SFD, 22 with DD, and eight with L-ORD were included. BM-RPE separation on SD-OCT demonstrated a high test-retest and interobserver reproducibility (intraclass correlation coefficients >0.9). BM-RPE separation was not identified in normal subjects. In SFD, there was greater BM-RPE separation in late-stage disease compared with intermediate-stage patients both at subfoveal (P < 0.05) and juxtafoveal (P < 0.01) locations. In DD, there was increased BM-RPE separation in late-stage disease compared with early stage at subfoveal (P < 0.001) and juxtafoveal (P < 0.05) topographies. There was no significant difference in BM-RPE separation between disease stages in L-ORD. Conclusions: BM-RPE separation is a novel, quantifiable phenotype in the three monogenic macular dystrophies studied, and may be an optical correlate of the histopathological thickening in BM that is known to occur. BM-RPE separation, as measured by OCT, varies with stage of disease in SFD and DD, but not in L-ORD. Translational Relevance: SFD, DD, and L-ORD are associated with BM thickening. In this group of patients, OCT assessment of macular structure identifies a separation of the usually single, hyperreflective line thought to represent BM and the overlying RPE. This separation is a novel and quantifiable feature of disease staging in SFD and DD.

Identifying the factors for improving quality of oral fluorescein angiography.

AIM: To evaluate the quality of oral fluorescein angiography (FA) in relation to food intake. METHODS: This is an observational, case-crossover study. We collected information from patients undergoing routine oral FA for retinal disease at the Shiley Eye Institute. Eighty patients (160 eyes) were analysed. Fasting and non-fasting images of the same patient were recorded, compared and analysed for different image quality parameters and clinical relevance by experienced retina specialists. RESULTS: When analysing the images, intergrader agreement was moderate to good with a Kappa averaging 0.60 (0.5-0.85). When patients were fasting pre-imaging, better angiography quality scores were achieved when compared with images taken when patients were non-fasting (mean 0.84 vs 0.72, p<0.001). Multivariate analysis showed that non-fasting patients with higher body mass index had the worst scores. Other clinical parameters, such as staining of drusen, staining of disciform scars or central and peripapillary atrophy, were also significantly better during the pre-fasting exam (p<0.001). Oral FA was approximately 22% faster (time to fluorescein dye appearance) under fasting conditions than non-fasting (mean±SD, minutes, 18.7±6.9 vs 25.14±8.1, p<0.001). CONCLUSION: Fasting oral FA provided significantly better quality images as well as faster optimal imaging times when compared with non-fasting oral FA. By improving its overall quality, oral FA could be a useful adjunctive examination to optical coherence tomography (OCT) and OCT angiography in patients who require FA studies but who have difficult access or refuse an invasive procedure.

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.].

Characterization of deeply embedded corneal foreign bodies with anterior segment optical coherence tomography.

PURPOSE: The purpose of the study was to describe findings demonstrated by anterior segment spectral domain optical coherence tomography (AS-OCT) in various types of deeply embedded corneal foreign bodies. METHODS: In this experimental study, an ex vivo model of calf eyes was used and seven different foreign bodies were deeply embedded in the cornea, consisting of five different materials: glass, plastic, metal, wood, and pencil graphite. The eyes were photographed and then scanned by AS-OCT. The images were analyzed to determine distinguishing characteristics for each material. RESULTS: Various materials presented unique characteristics in AS-OCT. The opaque materials (pencil graphite, metals, and wood) demonstrated a hyper-reflective anterior border, whereas the posterior border signal could not be clearly identified due to the shadowing effect. Moreover, a chain of signals was characteristic of both pencil graphite and metals though a "mirroring effect" was unique for metals. Wood, as an opaque material, appears as a hyper-reflective mass with a spectrum of penetrability depending on the degree of concentration. Transparent materials demonstrated hyper-reflective sharp borders when surrounded by air or fluid, as opposed to when being embedded purely in the corneal stroma. CONCLUSIONS: This study shows that AS-OCT was used to systematically define a novel set of distinguishing characteristics specific to various materials extruding from the cornea, fully embedded in the cornea, and intruding into the anterior chamber. Hopefully, the described characteristics of each material can aid clinicians in diagnosing the type of the material embedded and the depth of its involvement in ocular injury.

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.

COMPARISON OF RETINAL PATHOLOGY VISUALIZATION IN MULTISPECTRAL SCANNING LASER IMAGING.

PURPOSE: To compare retinal pathology visualization in multispectral scanning laser ophthalmoscope imaging between the Spectralis and Optos devices. METHODS: This retrospective cross-sectional study included 42 eyes from 30 patients with age-related macular degeneration (19 eyes), diabetic retinopathy (10 eyes), and epiretinal membrane (13 eyes). All patients underwent retinal imaging with a color fundus camera (broad-spectrum white light), the Spectralis HRA-2 system (3-color monochromatic lasers), and the Optos P200 system (2-color monochromatic lasers). The Optos image was cropped to a similar size as the Spectralis image. Seven masked graders marked retinal pathologies in each image within a 5 × 5 grid that included the macula. RESULTS: The average area with detected retinal pathology in all eyes was larger in the Spectralis images compared with Optos images (32.4% larger, P < 0.0001), mainly because of better visualization of epiretinal membrane and retinal hemorrhage. The average detection rate of age-related macular degeneration and diabetic retinopathy pathologies was similar across the three modalities, whereas epiretinal membrane detection rate was significantly higher in the Spectralis images. CONCLUSION: Spectralis tricolor multispectral scanning laser ophthalmoscope imaging had higher rate of pathology detection primarily because of better epiretinal membrane and retinal hemorrhage visualization compared with Optos bicolor multispectral scanning laser ophthalmoscope imaging.

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.

ANATOMICAL AND FUNCTIONAL TESTING IN DIABETIC PATIENTS WITHOUT RETINOPATHY: Results of Optical Coherence Tomography Angiography and Visual Acuity Under Varying Contrast and Luminance Conditions.

PURPOSE: To assess early retinal microvascular and functional changes in diabetic patients without clinical evidence of diabetic retinopathy with optical coherence tomography angiography and central visual analyzer. METHODS: This was an observational case-control study of diabetic patients without diabetic retinopathy and nondiabetic controls. Patients underwent optical coherence tomography angiography imaging and visual acuity testing using the central visual analyzer. The foveal avascular zone area and the capillary density in the superficial and deep capillary plexuses were measured manually by a masked grader. RESULTS: Sixty eyes from 35 diabetic patients were included in the study group, and 45 eyes from 31 nondiabetic patients were included in the control group. The foveal avascular zone area was not significantly different between the diabetic group and controls (both P > 0.05). The mean capillary density in the deep capillary plexus was significantly lower in diabetic eyes compared with control eyes (P = 0.04). The mean visual acuity in all central visual analyzer modules was significantly decreased in diabetic patients compared with controls (all P < 0.05). CONCLUSION: Optical coherence tomography angiography was able to detect retinal microvascular changes in the deep capillary plexus, and the central visual analyzer showed signs of decreased visual acuity under conditions simulating suboptimal contrast and glare in diabetic patients without diabetic retinopathy.

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.

Tear film evaluation by scanning laser ophthalmoscopy during retinal imaging.

PURPOSE:: Herein, we describe a novel finding which appears as a reticular pattern on multicolor confocal scanning laser ophthalmoscopy image during routine imaging of retina and we aim to show whether there is an association between this pattern and dry eye findings. MATERIALS AND METHODS:: A total of 162 eyes of 81 patients that were scheduled for a routine retinal imaging by scanning laser ophthalmoscopy at a vitreoretinal practice underwent dry eye evaluation including corneal and conjunctival lissamine green staining, fluorescein staining, tear break-up time, and tear meniscus height measurement before acquiring any images. Then, multicolor images were taken and graded for the severity of reticular pattern. RESULTS:: Among 150 eyes of 81 patients with gradable multicolor imaging, 45 eyes (30%) had some reticular pattern on multicolor image. Severity of reticular pattern on multicolor imaging was significantly correlated with total lissamine score (rho = 0.378, p = 0.007) and tear meniscus height (rho = -0.408, p = 0.011). Furthermore, they were found to be the best set of predictors for the severity pattern on multicolor imaging (odds ratio = 1.30, 95% confidence interval = 1.01-1.37, p = 0.027 and odds ratio = 0.25, 95% confidence interval = 0.128-0.342, p < 0.001, respectively). CONCLUSION:: Reticular pattern seen on multicolor image while acquiring retinal images using scanning laser ophthalmoscopy may be related to tear film instability. Further modulations of the scanning laser ophthalmoscopy instrument will likely improve this indicator of dry eye syndrome.

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.

QUANTITATIVE ANALYSIS OF THE INNER RETINAL LAYER THICKNESSES IN AGE-RELATED MACULAR DEGENERATION USING CORRECTED OPTICAL COHERENCE TOMOGRAPHY SEGMENTATION.

PURPOSE: To characterize inner retinal damage in patients with dry age-related macular degeneration (AMD) using high-resolution spectral domain optical coherence tomography images. METHODS: Sixty eyes of 60 patients with AMD were categorized using the Age-Related Eye Disease Study (AREDS) severity scale. Spectral domain optical coherence tomography images of these patients were quantified by manually correcting the segmentation of each retinal layer, including the retinal nerve fiber layer, ganglion cell layer, and inner plexiform layer to ensure accurate delineation of layers. The mean ganglion cell complex thickness values (ganglion cell layer + inner plexiform layer + retinal nerve fiber layer) were compared with 30 eyes of 30 healthy subjects. RESULTS: Ninety percent of eyes (81 eyes) required manual correction of segmentation. Compared with healthy subjects, mean ganglion cell complex thicknesses significantly decreased in more advanced dry AMD eyes, and this decrease was predominantly related to a change in inner plexiform layer thickness. There was no significant difference in thickness-related measurements between milder dry AMD (AREDS-2) eyes and healthy eyes (P > 0.05). CONCLUSION: In patients with dry AMD, automatic optical coherence tomography segmentation algorithms may be erroneous. As the severity of dry AMD increases, the inner plexiform layer layer becomes thinned, suggesting that transsynaptic degeneration may be occurring, as the photoreceptor layer is affected by AMD.