Long-term Follow-Up and Regeneration of Retinal Pigment Epithelium (RPE) after Tears of the Epithelium in Exudative Age-Related Macular Degeneration (AMD).

BACKGROUND: The goals of this study are to evaluate potential long-term visual deterioration associated with retinal pigment epithelial (RPE) tears in patients with neovascular age-related macular degeneration (nAMD) and to find treatment-related and morphological factors that might influence the outcomes. PATIENTS AND METHODS: This retrospective study enrolled 21 eyes of 21 patients from the database of Vista Eye Clinic Binningen, Switzerland, diagnosed with RPE tears, as confirmed by spectral domain optical coherence tomography (SD-OCT), with a minimum follow-up period of 12 months. Treatment history before and after RPE rupture with anti-VEGF therapy, visual acuity, and imaging (SD-OCT) were analyzed and statistically evaluated for possible correlations. RESULTS: Mean patient age was 80.5 ± 6.2 years. The mean length of total follow-up was 39.7 ± 13.9 months. The mean pigment epithelial detachment (PED) height increased by 363.8 ± 355.5 µm from the first consultation to 562.8 ± 251.5 µm at the last consultation prior to rupture. Therefore, a higher risk of RPE rupture is implied as a result of an increase in PED height (p = 0.004, n = 14). The mean visual acuity before rupture was 66.2 ± 16.0 letters. Mean visual acuity deteriorated to 60.8 ± 18.6 letters at the first consultation after rupture (p = 0.052, n = 21). A statistically nonsignificant decrease in vision was noted in the follow-up period. After 2 years, the mean BCVA decreased by 10.5 ± 23.7 ETDRS letters (p = 0.23, n = 19). PED characteristics before rupture and amount of anti-VEGF injections after rupture did not affect the visual outcome. None of the 21 patients included in our study showed a visual improvement in the long-term follow-up. RPE atrophy increased significantly from 3.35 ± 2.94 mm2 (baseline) to 6.81 ± 6.25 mm2 over the course of 2 years (p = 0.000 013, n = 20). CONCLUSIONS: The overall mean vision decrease after rupture was without statistical significance. There was no significant change in BCVA at the 2-year follow-up, independent of the amount of anti-VEGF injections provided. In this study, there was a significant increase in RPE defect over a follow-up of 2 years, implying progression of contraction of RPE and/or macular atrophy.

Pigment epithelial detachment composition indices (PEDCI) in neovascular age-related macular degeneration.

We provide an automated analysis of the pigment epithelial detachments (PEDs) in neovascular age-related macular degeneration (nAMD) and estimate areas of serous, neovascular, and fibrous tissues within PEDs. A retrospective analysis of high-definition spectral-domain OCT B-scans from 43 eyes of 37 patients with nAMD with presence of fibrovascular PED was done. PEDs were manually segmented and then filtered using 2D kernels to classify pixels within the PED as serous, neovascular, or fibrous. A set of PED composition indices were calculated on a per-image basis using relative PED area of serous (PEDCI-S), neovascular (PEDCI-N), and fibrous (PEDCI-F) tissue. Accuracy of segmentation and classification within the PED were graded in masked fashion. Mean overall intra-observer repeatability and inter-observer reproducibility were 0.86 ± 0.07 and 0.86 ± 0.03 respectively using intraclass correlations. The mean graded scores were 96.99 ± 8.18, 92.12 ± 7.97, 91.48 ± 8.93, and 92.29 ± 8.97 for segmentation, serous, neovascular, and fibrous respectively. Mean (range) PEDCI-S, PEDCI-N, and PEDCI-F were 0.253 (0-0.952), 0.554 (0-1), and 0.193 (0-0.693). A kernel-based image processing approach demonstrates potential for approximating PED composition. Evaluating follow up changes during nAMD treatment with respect to PEDCI would be useful for further clinical applications.

NINE-YEAR PROGRESSION OF PENTOSAN MACULOPATHY WITH MULTIMODAL RETINAL IMAGING.

BACKGROUND/PURPOSE: The purpose of this study was to describe the characteristic pattern of progression of pentosan polysulfate (PPS) maculopathy with multimodal retinal imaging in two patients, including one with over 9 years of follow-up. METHODS: Two patients with PPS maculopathy were sequentially evaluated with near-infrared reflectance (NIR) and optical coherence tomography. RESULTS: Near-infrared reflectance showed characteristic centrifugal progression of the parafoveal hyperreflective lesions toward the vascular arcades with the development of hyporeflective areas in both cases. Optical coherence tomography demonstrated focal retinal pigment epithelium (RPE) thickening that corresponded to the hyperreflective lesions on NIR. On subsequent optical coherence tomography scans, the hyperreflective areas resolved with the development of ellipsoid zone attenuation, RPE disruption, and atrophy, which colocalized with hyporeflectivity on NIR. CONCLUSION: This report describes the progression of pentosan polysulfate maculopathy over almost 10 years of PPS treatment and highlights the importance of NIR as a tool for the diagnosis and monitoring of PPS maculopathy. Pentosan polysulfate lesions present as areas of focal RPE thickening with ensuing development of ellipsoid zone loss and RPE drop-out. The pathophysiology of PPS toxicity is unknown and may either result from primary RPE or choroidal toxicity.

Simple Congenital Hamartoma of Retinal Pigment Epithelium.

A 45-year female presented in the Outpatient Department of a tertiary care hospital of Lahore with dimness of vision in the right eye. Her history revealed that the patient had noticed decreased vision since her childhood. Fundus examination revealed a jet-black slightly raised lesion about the size of »-disc diameter, located in the centre of macula. Optical coherence tomography (OCT) showed a highly hyper-reflective lesion at the fovea with sharp steep shadowing of the underlying structures due to backscattering. We excluded congenital hypertrophy of the retinal pigment epithelium (CHRPE) from our differential diagnosis, as solitary CHRPE is a flat well-demarcated lesion at the level of retinal pigment epithelium (RPE). Adenoma of RPE was eliminated as it has a large feeding and draining blood vessels with intra- and sub-retinal exudation. Choroid and surrounding retina was normal in our patient, which was helpful in differentiating it from choroidal nevus/choroidal melanoma. Our final diagnosis was simple congenital hamartoma of RPE. Key Words: Hamartoma, Retinal pigment epithelium, Macula.

RESTORATION PROCESS OF THE OUTER RETINAL LAYERS AFTER SURGICAL MACULAR HOLE CLOSURE.

PURPOSE: To investigate the interrelationship among the outer retinal layers after macular hole surgery and elucidate the restoration process. METHODS: This retrospective observational study included 50 eyes of 47 consecutive patients with closed macular holes in the first vitrectomy. Optical coherence tomography was obtained before surgery; at 1, 3, and 6 months postsurgery; and at the last visit. The complete continuous layer rate and mean defect length were evaluated for the outer nuclear layer (ONL), external limiting membrane (ELM), and ellipsoid zone (EZ). RESULTS: At all postoperative visits, the complete continuous layer rate was in the descending order of ELM, ONL, and EZ and the mean defect length was in the ascending order of ELM, ONL, and EZ. External limiting membrane was necessary for ONL restoration. External limiting membrane and ONL were necessary for EZ restoration. Hyperreflective protrusions were observed from the area lacking ELM into the subretinal space after surgery. Ellipsoid zone was not formed in coexistence with the hyperreflective protrusions. Intermediate reflective protrusions appeared under the ONL plus ELM after surgery and were eventually replaced by EZ. CONCLUSION: Restoration of the outer retinal layers after surgical macular hole closure occurs in the order of ELM, ONL, and EZ.

Near infrared autofluorescence imaging of retinal pigmented epithelial cells using 663 nm excitation.

PURPOSE: Fundus autofluorescence (AF) using adaptive optics scanning laser ophthalmoscopy (AOSLO) enables morphometric analysis of individual retinal pigmented epithelial (RPE) cells. However, only a few excitation wavelengths in the visible and near-infrared have been evaluated. Visible light excitation (<600 nm) presents additional safety hazards and is uncomfortable for patients. Near-infrared excitation (>700 nm) overcomes those problems but introduces others, including decreased AF signal and cone signatures that obscure RPE structure. Here we investigated the use of an intermediate wavelength, 663 nm, for excitation and compared it to 795 nm. METHODS: Subjects were imaged using AOSLO equipped with a detection channel to collect AF emission between 814 and 850 nm. Two light sources (663 and 795 nm) were used to excite the retinal fluorophores. We recorded 90 s videos and registered them with custom software to integrate AF images for analysis. RESULTS: We imaged healthy eyes and an eye with pattern dystrophy. Similar AF microstructures were detected with each excitation source, despite ~4 times lower excitation power with 663 nm. The signal-to-noise values showed no meaningful difference between 663 nm and 795 nm excitation and a similar trend was observed for image contrast between the two excitation wavelengths. CONCLUSIONS: Lower light levels can be used with shorter wavelength excitation to achieve comparable images of the microstructure of the RPE as have been obtained using higher light levels at longer wavelengths. Further experiments are needed to fully characterize AF across spectrum and determine the optimal excitation and emission bandwidths that balance efficiency, patient comfort, and efficacy.

Multimodal imaging in a patient with combined hamartoma of the retina and retina pigment epithelium.

Combined hamartoma of the retina and retinal pigment epithelium is a rare, benign intraocular tumor. Hamartoma of the retina and retinal pigment epithelium has been described in the literature as a condition presenting with variable retinal damage, ranging from partial epiretinal involvement to complete distortion of the retinal layers and retinal pigment epithelium. We report the case of an 8-year-old girl presenting with longstanding strabismus who was diagnosed with Hamartoma of the retina and retinal pigment epithelium based on multimodal imaging assessment. We explored the particular imaging findings from studies using spectral-domain optical coherence tomography, fundus autofluorescence, optical coherence tomography angiography, and fluorescein angiography.

Histopathology of myopic cobblestones.

PURPOSE: To search for the histological correlate of peripheral 'cobblestones' in highly myopic eyes. METHODS: The histomorphometric investigation included histologic sections of enucleated eyes of Caucasian patients. Using light microscopy, we measured the thickness of the retina, Bruch's membrane (BM) and choriocapillaris. RESULTS: The study included 50 eyes (mean age:60.6 ± 18.7 years;axial length:26.5 ± 3.8 mm), with cobblestone regions detected in 7 eyes. BM thickness and choriocapillaris thickness in the cobblestone region were thinner (1.1 ± 0.2 µm versus 2.4 ± 0.8 µm; p < 0.001 and 1.6 ± 0.5 µm versus 2.6 ± 1.9 µm; p = 0.02, respectively), and just outside of the cobblestone region they were thicker (3.3 ± 0.6 µm versus 2.4 ± 0.8 µm; p = 0.005 and 5.7 ± 1.6 µm versus 2.6 ± 1.9 µm; p = 0.002, respectively) than in corresponding regions of eyes without cobblestones. Within the group of eyes with cobblestones, BM thickness (1.1 ± 0.2 mm versus 3.3 ± 0.6 mm; p < 0.001), choriocapillaris thickness (1.6 ± 0.5 mm versus 5.7 ± 1.6 mm; p < 0.001) and choriocapillaris density (48±15 µm/300 µm versus 159 ± 66 µm/300 µm;PP=0.002) were significantly lower in the cobblestone region than just outside of the cobblestone region. The cobblestone regions were characterized by firm adhesion of disorganized retina with thinned BM, few retinal pigment epithelium (RPE) islands within cobblestone regions, and absence of regional scleral or overall choroidal thinning. BM was mono-layered within, and double-layered outside of cobblestone regions, with the inner layer missing within the cobblestone region (except for the RPE islands). CONCLUSIONS: Peripheral cobblestone regions in highly myopic eyes are characterized by marked BM thinning with absence of an inner BM layer, almost complete RPE absence, choriocapillaris thinning and firm connection of a disorganized retina to BM. These findings may help elucidating the process of axial elongation in myopic eyes.

PIGMENT EPITHELIAL DETACHMENT IN AGE-RELATED MACULAR DEGENERATION: Long-Term Visual Acuity May Improve With Higher Injection Index.

PURPOSE: To define injection index (II) and assess its impact on visual acuity (VA) in pigment epithelial detachment from age-related macular degeneration over 5 years. METHODS: Injection index is defined as the mean anti-vascular endothelial growth factor injections per year from presentation. A retrospective study of 256 eyes in 213 patients was performed. Patients were stratified by II (high: ≥9, low: <9). RESULTS: Baseline characteristics showed no differences across II groups. Mean (range) follow-up, in years, was 5.02 (1.04-12.74) for all patients. Mean logMAR VA (Snellen VA) were 0.60 (20/80) and 0.56 (20/73) at baseline, 0.52 (20/66) and 0.59 (20/78) at Year 1, 0.45 (20/56) and 0.67 (20/94) at Year 2, 0.38 (20/48) and 0.66 (20/91) at Year 3, 0.41 (20/51) and 0.89 (20/155) at Year 4, and 0.35 (20/45) and 0.79 (20/123) at Year 5 for the high and low II groups, respectively. Linear regression analysis showed a gain of 0.5 approxETDRS letters with each additional injection per year. CONCLUSION: Increased II was associated with better mean VA, suggesting that long-term continuous vascular endothelial growth factor suppression may improve VA in eyes thought to carry poor prognoses.

Intraocular iron injection induces oxidative stress followed by elements of geographic atrophy and sympathetic ophthalmia.

Iron has been implicated in the pathogenesis of age-related retinal diseases, including age-related macular degeneration (AMD). Previous work showed that intravitreal (IVT) injection of iron induces acute photoreceptor death, lipid peroxidation, and autofluorescence (AF). Herein, we extend this work, finding surprising chronic features of the model: geographic atrophy and sympathetic ophthalmia. We provide new mechanistic insights derived from focal AF in the photoreceptors, quantification of bisretinoids, and localization of carboxyethyl pyrrole, an oxidized adduct of docosahexaenoic acid associated with AMD. In mice given IVT ferric ammonium citrate (FAC), RPE died in patches that slowly expanded at their borders, like human geographic atrophy. There was green AF in the photoreceptor ellipsoid, a mitochondria-rich region, 4 h after injection, followed later by gold AF in rod outer segments, RPE and subretinal myeloid cells. The green AF signature is consistent with flavin adenine dinucleotide, while measured increases in the bisretinoid all-trans-retinal dimer are consistent with the gold AF. FAC induced formation carboxyethyl pyrrole accumulation first in photoreceptors, then in RPE and myeloid cells. Quantitative PCR on neural retina and RPE indicated antioxidant upregulation and inflammation. Unexpectedly, reminiscent of sympathetic ophthalmia, autofluorescent myeloid cells containing abundant iron infiltrated the saline-injected fellow eyes only if the contralateral eye had received IVT FAC. These findings provide mechanistic insights into the potential toxicity caused by AMD-associated retinal iron accumulation. The mouse model will be useful for testing antioxidants, iron chelators, ferroptosis inhibitors, anti-inflammatory medications, and choroidal neovascularization inhibitors.

Changes in entropy on polarized-sensitive optical coherence tomography images after therapeutic subthreshold micropulse laser for diabetic macular edema: A pilot study.

PURPOSE: To investigate the dynamics of the healing process after therapeutic subthreshold micropulse laser (SMPL) for diabetic macular edema (DME) using polarization-sensitive optical coherence tomography (PS-OCT). METHODS: Patients with treatment-native or previously-treated DME were prospectively imaged using PS-OCT at baseline, 1, 2, 3, and 6 months. The following outcomes were evaluated: changes in the entropy value per unit area (pixel2) in the retinal pigment epithelium (RPE) on the B-scan image; changes in the entropy value in each stratified layer (retina, RPE, choroid) based on the ETDRS grid circle overlaid with en face entropy mapping, not only the whole ETDRS grid area but also a sector irradiated by the SMPL; and the relationship between edema reduction and entropy changes. RESULTS: A total of 11 eyes of 11 consecutive DME patients were enrolled. No visible signs of SMPL treatment were detected on PS-OCT images. The entropy value per unit area (pixel2) in the RPE tended to decrease at 3 and 6 months from baseline (35.8 ± 17.0 vs 26.1 ± 9.8, P = 0.14; vs 28.2 ± 18.3, P = 0.14). Based on the en face entropy mapping, the overall entropy value did not change in each layer in the whole ETDRS grid; however, decrease of entropy in the RPE was observed at 2, 3, and 6 months post-treatment within the SMPL-irradiated sectors (P < 0.01, each). There was a positive correlation between the change rate of retinal thickness and that of entropy in the RPE within the SMPL-irradiated sector at 6 months (r2 = 0.19, P = 0.039). CONCLUSION: Entropy measured using PS-OCT may be a new parameter that facilitates objective monitoring of SMPL-induced functional changes in the RPE that could not previously be assessed directly. This may contribute to a more promising therapeutic evaluation of DME. CLINICAL TRIAL: This clinical study was registered in UMIN-CTR (ID: UMIN000042420).

Retinal and Choroidal Pathologies in Aged BALB/c Mice Following Systemic Neonatal Murine Cytomegalovirus Infection.

Although pathologies associated with acute virus infections have been extensively studied, the effects of long-term latent virus infections are less well understood. Human cytomegalovirus, which infects 50% to 80% of humans, is usually acquired during early life and persists in a latent state for the lifetime. The purpose of this study was to determine whether systemic murine cytomegalovirus (MCMV) infection acquired early in life disseminates to and becomes latent in the eye and if ocular MCMV can trigger in situ inflammation and occurrence of ocular pathology. This study found that neonatal infection of BALB/c mice with MCMV resulted in dissemination of virus to the eye, where it localized principally to choroidal endothelia and pericytes and less frequently to the retinal pigment epithelium (RPE) cells. MCMV underwent ocular latency, which was associated with expression of multiple virus genes and from which MCMV could be reactivated by immunosuppression. Latent ocular infection was associated with significant up-regulation of several inflammatory/angiogenic factors. Retinal and choroidal pathologies developed in a progressive manner, with deposits appearing at both basal and apical aspects of the RPE, RPE/choroidal atrophy, photoreceptor degeneration, and neovascularization. The pathologies induced by long-term ocular MCMV latency share features of previously described human ocular diseases, such as age-related macular degeneration.

Clinical and Morphologic Characteristics of Extracellular Signal-Regulated Kinase Inhibitor-Associated Retinopathy.

PURPOSE: To investigate clinical and morphologic characteristics of serous retinal disturbances in patients taking extracellular signal-regulated kinase (ERK) inhibitors. DESIGN: Single-center retrospective study of prospectively collected data. PARTICIPANTS: Of 61 patients receiving ERK inhibitors for treatment of metastatic cancer, this study included 40 eyes of 20 patients with evidence of retinopathy confirmed by OCT. METHODS: Clinical examination, fundus photography, and OCT were used to evaluate ERK inhibitor retinopathy. The morphologic features, distribution, and location of fluid foci were evaluated serially. Visual acuity (VA) and choroidal thickness measurements were compared at baseline, fluid accumulation, and resolution. MAIN OUTCOME MEASURES: Characteristics of treatment-emergent choroid and retinal OCT abnormalities as compared with baseline OCT findings and the impact of toxicity on VA. RESULTS: Of 20 patients with retinopathy, most showed fluid foci that were bilateral (100%), multifocal in each eye (75%), and with at least 1 focus involving the fovea (95%). All subretinal fluid foci occurred between the interdigitation zone and an intact retinal pigment epithelium. No statistical difference was found in choroidal thickness at fluid accumulation and resolution compared with baseline. Forty-five percent of eyes showed evidence of concomitant intraretinal edema localized to the outer nuclear layer. At the time of fluid accumulation, 57.5% eyes showed a decline in VA (mainly by 1-2 lines from baseline). For all eyes with follow-up, the subretinal fluid and intraretinal edema were reversible and resolved without medical intervention, and best-corrected VA at fluid resolution was not statistically different from baseline. Concomitant intraretinal fluid was not associated with worsening of VA. No patient discontinued or decreased drug dose because of retinopathy. CONCLUSIONS: This study showed that ERK inhibitors may cause subretinal fluid foci with unique clinical and morphologic characteristics. The observed foci were similar to mitogen-activated protein kinase kinase (MEK) inhibitor-associated retinopathy and distinct from central serous chorioretinopathy. However, unlike with MEK inhibitors, an increased occurrence of concomitant intraretinal fluid without significant additive visual impact seems to occur with ERK inhibitors. In this series, ERK inhibitors did not cause irreversible loss of vision or serious eye damage; retinopathy was self-limited and did not require medical intervention.

Pentosan Polysulfate Maculopathy: Prevalence, Spectrum of Disease, and Choroidal Imaging Analysis Based on Prospective Screening.

PURPOSE: To describe the prevalence and spectrum of disease of pentosan polysulfate (PPS) maculopathy in a large multimodal retinal imaging study and to report the results of choroidal vascularity index (CVI) analysis. DESIGN: Prospective cohort study Methods: Of 741 patients prescribed PPS within a large university database, 100 (13.4%) with any consumption agreed to participate in a prospective screening investigation. Multimodal retinal imaging including near-infrared reflectance (NIR), fundus autofluorescence (FAF), and spectral domain optical coherence tomography (SD-OCT) was performed in all patients. Characteristic findings of affected patients were identified, and affected and unaffected cohorts were compared. CVI, defined as stromal choroidal area (SCA) divided by the total choroidal area, was analyzed. RESULTS: The prevalence of PPS maculopathy was 16%. NIR illustrated punctate hyperreflective lesions with early presentation. FAF illustrated a speckled macular network of hypo- and hyperautofluorescence colocalized with multifocal hyperreflective retinal pigment epithelial lesions on SD-OCT. Advanced cases demonstrated varying degrees of atrophy. The affected cohort exhibited significantly greater mean PPS therapy duration, mean daily dosage, and mean cumulative dosage (19.5±5.5 years, 433.9±137.6 mg, 3,103.1±1,402.2 g) compared with the unaffected cohort (7.1±6.6 years, 291.6±177.6 mg, 768.4±754.8 g). SCA was significantly lower and CVI was significantly greater in the affected vs the unaffected group. CONCLUSIONS: This prospective cohort study identified a prevalence of PPS maculopathy of 15%-20% among PPS users who agreed to participate. A spectrum of findings may be observed with multimodal retinal imaging. Significant choroidal abnormalities associated with this characteristic maculopathy may provide surrogate markers of macular toxicity.

Longitudinal Assessment of Ellipsoid Zone Integrity, Subretinal Hyperreflective Material, and Subretinal Pigment Epithelium Disease in Neovascular Age-Related Macular Degeneration.

PURPOSE: To assess longitudinally the effect of anti-vascular endothelial growth factor (VEGF) treatment on ellipsoid zone (EZ) integrity, subretinal hyperreflective material (SHRM), and the sub-retinal pigment epithelium (sub-RPE) compartment in eyes with neovascular age-related macular degeneration (nAMD). DESIGN: Post hoc analysis of the OSPREY clinical trial, a prospective, double-masked, phase 2 study comparing brolucizumab 6 mg with aflibercept 2 mg over 56 weeks. PARTICIPANTS: Participants with treatment-naïve nAMD at the initiation of the trial were included in the analysis. METHODS: Eyes were evaluated with spectral-domain OCT at 4-week intervals in the OSPREY trial (n = 81). Spectral-domain OCT scans collected from each visit were segmented automatically using a proprietary, machine learning-enabled higher-order feature-extraction platform for retinal layer, SHRM, and sub-RPE boundary lines, which were evaluated and corrected as needed by masked trained graders. The current analysis focused only on patients evaluated with the Cirrus (Zeiss) platform (n = 28). MAIN OUTCOME MEASURES: Outcome measures included change from baseline in EZ-RPE (i.e., photoreceptor outer segment) volume, EZ-RPE central subfield thickness (CST), total EZ attenuation, SHRM volume, SHRM CST, and total sub-RPE volume. The correlation between each of these measures and best-corrected visual acuity (BCVA) at each visit was evaluated. RESULTS: EZ-RPE volume and EZ-RPE CST showed significant increases, and total EZ attenuation, SHRM volume, SHRM CST, and total sub-RPE volume showed significant decreases from baseline at each visit from weeks 4 through 56 (P < 0.05 at each visit). Ellipsoid zone integrity measures and SHRM volume correlated significantly with BCVA at most visits (P < 0.05). No significant correlation was found between total sub-RPE volume and BCVA. CONCLUSIONS: EZ integrity, SHRM, and sub-RPE disease features in eyes with nAMD showed improvement as early as week 4 of anti-VEGF treatment. EZ integrity measures and SHRM volume were predictors of visual acuity over the first year of treatment.

ASSESSMENT OF EARLY CHANGES IN SPECTRAL DOMAIN-OPTICAL COHERENCE TOMOGRAPHY AFTER INITIATION OF TREATMENT WITH INTRAVITREAL AFLIBERCEPT (EYLEA) OVER A 12-WEEK PERIOD FOR PATIENTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: A Multicenter French Study (START).

PURPOSE: To assess early changes in spectral-domain optical coherence tomography during the loading phase with intravitreal aflibercept therapy in patients with neovascular age-related macular degeneration. METHODS: In this prospective, open-label, single-arm, multicenter study, patients with neovascular age-related macular degeneration, who were antivascular endothelial growth factor treatment-naïve, received three monthly initial doses of intravitreal aflibercept 2 mg. The primary outcome was the proportion of patients with dry spectral-domain optical coherence tomography at 12 weeks, defined as an absence of intraretinal edema, intraretinal cysts, subretinal fluid, and subretinal pigment epithelium fluid. RESULTS: Fifty eyes of 50 patients were investigated. At 12 weeks, 34.0% (17/50) had dry spectral-domain optical coherence tomography. Marked reductions were observed for all other spectral-domain optical coherence tomography parameters. The mean macular central thickness fell significantly from 463.2 ± 184.3 µm at baseline to 288.9 ± 76.8 µm at Week 12 (P < 0.0001). The mean best-corrected visual acuity also improved significantly from 61.0 ± 16.0 letters at baseline to 66.6 ± 19.0 letters at Week 12 (P = 0.0006). CONCLUSION: The anatomic and functional outcomes improved over the 12-week study period. All outcome variables peaked after the third aflibercept injection, confirming the benefit of three initial doses.