The Effects of Treatment Regimen on the Initial Management of Macular Neovascularization Subtypes in Age-Related Macular Degeneration.

INTRODUCTION: The aim of this study was to evaluate the effect of initial treatment regimen individualization (pro re nata or treat-and-extend [TAE]), according to macular neovascularization (MNV) subtype, on the functional and anatomical response in neovascular age-related macular degeneration (nAMD). The secondary objective was to compare the treatment burden between each MNV subtype. METHODS: Consecutive treatment-naïve nAMD patients were retrospectively included. MNV subtype was graded by 2 independent blinded investigators on multimodal imaging. Functional and anatomical outcomes were analysed according to treatment regimen and MNV subtypes. RESULTS: A total of 281 eyes from 243 patients were included in the study. According to the treatment regimen, there was no significant difference in best-corrected visual acuity gain within the first 2 years of treatment for type 1 (p = 0.106) and type 3 MNV (p = 0.704). Conversely, there was a significant difference in favour of TAE regimen for type 2 (p = 0.017) and type 4 MNV (p = 0.047). Type 1 MNV had a higher proportion of visits with subretinal fluid (p = 0.0007) but not with intraretinal fluid (p = 0.22). The mean interval between the last 2 injections was significantly shorter for type 1 MNV (p = 0.0045). CONCLUSION: The individualization of the initial treatment protocol according to MNV subtype can improve the functional outcome and may decrease the treatment burden.

PREVALENCE OF RETICULAR PSEUDODRUSEN IN AGE-RELATED MACULAR DEGENERATION USING MULTIMODAL IMAGING.

PURPOSE: To determine the rate of reticular pseudodrusen (RPD) in age-related macular degeneration using multimodal imaging, including color fundus photography, the blue channel image of fundus photography, infrared reflectance, fundus autofluorescence, multicolor imaging, and spectral domain optical coherence tomography, as well as to compare the sensitivities and specificities of these modalities for detecting RPD. METHODS: This prospective study included 243 eyes from 125 consecutive patients with age-related macular degeneration. They underwent fundus examination including color fundus photography, blue channel, infrared reflectance, fundus autofluorescence, multicolor imaging, and spectral domain optical coherence tomography in both eyes. To be considered as having RPD, eyes had to have reticular patterns on spectral domain optical coherence tomography in a large studied cube of 30° × 25° or on infrared reflectance with at least one other examination. RESULTS: The mean age of the 125 patients was 81.1 years (± 8.1). Eighty-six patients (68.8%) were diagnosed with RPD. Spectral domain optical coherence tomography, infrared reflectance, and multicolor imaging had the highest sensitivity (99.3, 84.6, and 87.1%, respectively) and specificity (100%). The color fundus photography, blue channel, and fundus autofluorescence had lower sensitivity to detect RPD. CONCLUSION: Reticular pseudodrusen is frequently associated with soft drusen in patients with age-related macular degeneration. As RPD may be rarely located only in the perifoveal area, spectral domain optical coherence tomography with a larger cube (30 × 25°) than that usually used (20 × 20°) had the highest sensitivity and specificity to detect RPD and is recommended to optimize the rate of detection.

Effect of baseline fluid localization on visual acuity and prognosis in type 1 macular neovascularization treated with anti-VEGF.

PURPOSE: To assess the prognostic value of subretinal (SRF) and intraretinal fluid (IRF) localizations in type 1 macular neovascularization (MNV) due to age-related macular degeneration (AMD). SUBJECTS: Eyes were prospectively treated with anti-vascular epithelial growth factor (anti-VEGF) intravitreal injections (IVT) according to a Pro-Re-Nata (PRN) or Treat and Extend (TAE) regimen during 24 months. A total of 211 eyes with treatment-naïve type 1 MNV secondary to AMD were consecutively included. Eyes were divided between 2 groups according to the fluid localization: presence of SRF alone (SRF group), or presence of IRF associated or not with SRF (IRF ± SRF group). RESULTS: At baseline the mean BCVA was 66.2 letters. SRF was present in 94.8% of eyes, IRF in 30.8%, and both in 25.6%. Data were available for 201 eyes at 12 months, and 157 eyes at 24 months. The presence of IRF at baseline was associated with lower baseline BCVA and significantly lower BCVA at 12 months (p < 0.001) and 24 months (p < 0.001). Eyes with SRF alone displayed better visual outcomes (BCVA at month 12, SRF = 74.3 letters, IRF ± SRF = 56.9 letters). In the presence of baseline IRF, fibrosis (p = 0.03) and atrophy (p < 0.001) were more frequently found at 24 months. In a multivariate model, the presence of baseline IRF was significantly associated with lower BCVA at month 12 but not at month 24. CONCLUSION: In type 1 MNV, the presence of baseline IRF was associated with worse visual outcomes compared to SRF alone, and more frequent atrophy and fibrosis.

Subretinal fibrosis occurrence according to macular neovascularisation subtypes in neovascular age-related macular degeneration.

PURPOSE: To assess subretinal fibrosis (SF) occurrence in neovascular age-related macular degeneration (nAMD), according to macular neovascularisation (MNV) subtypes. METHODS: A Retrospective national multi centre cohort study included eyes with naive nAMD. Main outcome measures were, according to MNV subtypes, cumulative incidence for SF, risk factors, and best corrected visual acuity (BCVA) for 36 months. RESULTS: Four hundred and twenty eyes were included. Cumulative incidence of SF was 34.3% at 1 year, 39.0% at 2 years and 50.6% at 3 years. In multivariable analysis, Type 2 and mixed type 1 and 2 MNV were associated (p < 0.001) with a more frequent and rapid development of SF (respectively 85.5% and 81.0% at 1 year, then 95.8% and 93.1% at 3 years) than Types 1 and 3 (respectively 11.3% and 3.6% at 1 year, then 22.9% and 12.7% at 3 years). In Type 2 and mixed type 1 and 2 MNV combined, at baseline a worse BCVA (p = 0.02) and a higher maximal subretinal hyperreflective material (SHRM) thickness (p = 0.005) were associated with SF development at 3 years. In Type 1 MNV, the presence at baseline of intraretinal fluid (IRF) (p = 0.007) or SHRM (p < 0.001) and a higher percentage of visits with IRF (p < 0.001) or with SHRM (p < 0.001) were associated with SF occurrence. For Type 3 MNV, only a higher percentage of visits with SHRM (p = 0.001) was associated with SF. Including all MNV subtypes, eyes with a worse BCVA at baseline were associated with SF development (p < 0.001). Conversely, presence of SF at 3 years was associated with a worse baseline BCVA (p < 0.001). CONCLUSION: Occurrence of SF differs when considering apart MNV subtypes.

Anatomical-functional concordance of microperimetry and the simplified age-related macular degeneration study classification: A pilot study.

PURPOSE: The principal aim of this pilot study was to investigate the concordance between the different stages of Age-Related Macular Degeneration (AMD), as determined by the simplified classification of the Age Related Eye Disease Study Group (AREDS), and new evaluation criteria using a microperimetry system. METHODS: A complete eye examination and a microperimetry MAIATM (Macular Integrity Assessment, CenterVue, Padova, Italy) examination was performed on 59 eyes with early, intermediate or advanced AMD. We analysed 19 evaluation criteria for every clinical group category. RESULTS: There were 20 female and 12 male participants included with a median age of 74 years (min: 54, max: 87). Thirteen eyes (22%) were classified as category 1, 11 eyes (18.6%) as category 2, 17 eyes (28.8%) as category 3 and 18 eyes (30.6%) as category 4 AMD.All evaluated microperimetry criteria related to retinal sensitivity were found to have a statistically significant difference among the stages (p < 0.05). Fixation stability was unstable in 55.6% of the eyes classified as stage 4 (p = 0.001). The analysis of the distance between the two PRLs - PRL_initial and PRL_final was larger for the stage 4 (p = 0.0258). The mean sensitivity in stages 2 and 3 correlated with the presence or not of reticular pseudodrusen (p = 0.0137). CONCLUSIONS: The mean sensitivity and the categorized sensitivity (set to 25, 15 and 5 dB), the five higher and lower stimuli sensitivity appeared to be the most sensitive criteria to differentiate the four AMD categories. Microperimetry provides a new reproducible method of anatomical-functional macular analysis.

Polypoidal Choroidal Vasculopathy Diagnosis and Neovascular Activity Evaluation Using Optical Coherence Tomography Angiography.

PURPOSE: To examine choroidal neovascularization (CNV) characteristics in patients with exudative age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV), using swept-source optical coherence tomography angiography (SS-OCTA), and investigate agreement with OCT B-scan, fundus fluorescein angiography (FFA), and indocyanine green angiography (ICGA) by two different examiners. METHODS: This is a retrospective multicentric study that involved patients with a history of AMD and PCV. Examiner A, who had access to OCTA, B-scan OCT, FFA, and ICGA imaging, had to differentiate between AMD and PCV, study the activity of AMD using Coscas' criteria (active vs. quiescent), and categorize PCV subtypes, while examiner B had only access to OCTA. Then, the diagnostic concordance was assessed between both examiners. RESULTS: A total of 27 patients (11 females (40.7%) and 16 males (59.3%), P = 0.231) were included in the analysis. Among those, 13 patients presented with neovascular AMD and 14 patients with PCV. There were 92.3% of correct answers regarding appropriate diagnosis and lesion characterization among AMD patients, against 61.5% of correct answers among PCV patients. The overall interrater reliability agreement between examiners, using Cohen's kappa coefficient (κ) was 0.70 (0.5082-0.8916). Disagreement was found with one active AMD misdiagnosed as inactive AMD, three inactive PCV misdiagnosed as inactive AMD, and one inactive PCV misdiagnosed as active AMD. CONCLUSION: SS-OCTA alone remains limited in some specific phenotypes of PCV, which suggests the ongoing role of B-scan OCT associated with FFA and ICGA in the diagnosis of these conditions.

Idiopathic polypoidal choroidal vasculopathy in Caucasians: The POLYON real-life study in 50 naive patients.

OBJECTIVES: Polypoidal choroidal vasculopathy is a common disease in Asia, but it has been less described in the Caucasian population. The aim of this real-life observational study was to describe the diagnostic and therapeutic practices as well as the prognosis in this population. METHOD: Fifty Caucasian patients with polypoidal choroidal vasculopathy were included in this study. All patients underwent angiography to confirm the diagnosis. Patients were divided into two treatment groups: patients of group 1 only received anti-vascular endothelial growth factor injections and those of group 2 required photodynamic therapy rescue in addition to intravitreal injections in case of suboptimal (anatomically or functionally) response. Clinical (visual acuity, fundus examination), paraclinical (retinal pigment epithelium detachment height and central retinal thickness on optical coherence tomography), and therapeutic (number of intravitreal injections) criteria were analyzed after 24 months. RESULTS: Patient mean age was 73.9 ± 9.1 years, and half of the patients had age-related macular degeneration. In the whole cohort, the initial visual acuity was equivalent to the final visual acuity (59.9 ± 24.0 letters vs 62.5 ± 21.1 letters, p = 0.259). In group 1, the final visual acuity was significantly increased (from 56.9 ± 24.7 letters to 63.4 ± 21.6 letters, p = 0.016), while in group 2, it remained stable (from 61.7 ± 23.4 letters to 61.0 ± 21.4 letters, p = 0.249). The number of intravitreal injections was similar between both groups. CONCLUSION: In a Caucasian population, polypoidal choroidal vasculopathy seems to have a later onset. A non-standardized management allows stabilizing the functional prognosis. Patients requiring photodynamic therapy rescue have a poorer prognosis.

Dark and white lesions observed in central serous chorioretinopathy on optical coherence tomography angiography.

PURPOSE: To describe abnormal dark (hyposignal) and white (hypersignal) lesions observed on optical coherence tomography angiography in central serous chorioretinopathy. METHODS: Prospective, multicenter, and descriptive study including patients with active or quiescent central serous chorioretinopathy. All patients had undergone a complete ophthalmic examination. RESULTS: Abnormal dark lesions were detected as "dark spots" and "dark areas" on optical coherence tomography angiography. A "dark spot" could correspond to six different abnormalities: pigment epithelium detachment, subretinal deposit, "Lucency" within surrounding subretinal fibrin, choroidal cavitation, choroidal excavation, and choroidal fluid. A "dark area" could be related to a serous retinal detachment or choriocapillary compression. Abnormal white lesions were also detected: A "white spot" could correspond with the leaking point on fluorescein angiography or with hyper-reflective dots; A "white filamentous pattern" at the Brüch's membrane level corresponded to abnormal choroidal neovascular vessels. CONCLUSION: A semiology is described using optical coherence tomography angiography in central serous chorioretinopathy as abnormal dark and white lesions. Multimodal imaging is mandatory in addition to optical coherence tomography angiography to diagnose non-neovascular retinal and choroidal central serous chorioretinopathy lesions. However, optical coherence tomography angiography alone is helpful in detecting choroidal neovascular membrane in central serous chorioretinopathy.

Morphological Predictive Features on Spectral-Domain Optical Coherence Tomography for Visual Outcomes in Neovascular Age-Related Macular Degeneration Treated with Ranibizumab.

PURPOSE: To identify spectral-domain optical coherence tomography (SD-OCT) predictive morphological features for the outcome of Ranibizumab therapy for neovascular age-related macular degeneration (AMD). METHODS: This is a retrospective multicentric study that involved 64 eyes with naïve AMD. Patients who received three monthly intravitreal injections of Ranibizumab were stratified into (1) "responders" [≥ 5 letters gain on Early Treatment Diabetic Retinopathy Study (ETDRS) scale] and (2) "nonresponders" (< 5 letters gain). Best-corrected visual acuity (BCVA) and SD-OCT morphological features were compared at baseline and one month after three consecutive injections of Ranibizumab. Univariate and multivariate analyses were carried out to correlate these morphological features with the change in BCVA. RESULTS: Among the 64 patients enrolled, 40 (62.5%) were "responders" and 24 (37.5%) "nonresponders". Age, sex, and BCVA were comparable between both groups. A multivariate correlational analysis found that subfoveal choroidal thickness (SFCT) and the presence of pigment epithelial detachment (PED) > 250 µm at baseline were two independent prognostic indicators of final BCVA. No other SD-OCT morphological studied features seem to affect final BCVA after Ranibizumab treatment. CONCLUSION: SFCT and the presence of PED > 250 µm are two significant biomarkers that may predict improvement after Ranibizumab therapy for AMD. These markers may guide ophthalmologists' treatment decision under financial constraints and limited time.

"En-face" spectral-domain optical coherence tomography findings in multiple evanescent white dot syndrome.

Purpose. The recent use of "en-face" enhanced-depth imaging spectral-domain optical coherence tomography (EDI SD-OCT) helps distinguish the retinal layers involved in the physiopathology of multiple evanescent white dot syndrome (MEWDS). Methods. Four patients presenting with MEWDS underwent a comprehensive ocular examination including C-scan ("en-face") EDI SD-OCT at the initial visit and during follow-up. Results. C-scans combined with the other multimodal imaging enabled the visualization of retinal damage. Acute lesions appeared as diffuse and focal disruptions occurring in the ellipsoid and interdigitation zones. The match between autofluorescence imaging, indocyanine green angiography, and "en-face" OCT helped identify the acute microstructural damages in the outer retina further than the choroid. Follow-up using "en-face" EDI-OCT revealed progressive and complete recovery of the central outer retinal layers. Conclusion. "En-face" EDI SD-OCT identified the site of initial damage in MEWDS as the photoreceptors and the interdigitation layers rather than the choroid. Moreover, "en-face" OCT is helpful in the follow-up of these lesions by being able to show the recovery of the outer retinal layers.

Association of reticular pseudodrusen and early onset drusen.

Purpose. To report an association between reticular pseudodrusen, located above the retinal pigment epithelium (RPE), and Early Onset Drusen (EOD) as described using Spectral-Domain Optical Coherence Tomography (SD-OCT). Methods. Eight patients (16 eyes) with EOD were examined. EOD were classified into three entities called Large Colloid Drusen (LCD), Malattia Leventinese (ML), and Cuticular Drusen (CD). Best-corrected visual acuity, fundus examination, color fundus photographs, fundus autofluorescence (FAF), fluorescein angiography (FA), indocyanine green angiography (ICGA), and SD-OCT were performed in all study patients. Results. Four patients had LCD, 2 had ML, and 2 had CD. Reticular pseudodrusen were observed with SD-OCT in all study patients; all these patients had hyperreflective lesions above and below the RPE. Conclusion. Early Onset Drusen appear to be associated with reticular pseudodrusen. SD-OCT is helpful in distinguishing the location of the deposits that are above and below the RPE in EOD. Further studies are needed to understand the role of reticular pseudodrusen in the pathophysiology of EOD.

B-scan and "en-face" spectral-domain optical coherence tomography imaging for the diagnosis and followup of acute retinal pigment epitheliitis.

Purpose. To report B-scan and "En-face" spectral-domain optical coherence tomography (SD-OCT) findings in acute retinal pigment epitheliitis (ARPE). Methods. Two patients (3 eyes) with ARPE were examined. Fluorescein and indocyanine green (ICGA) angiography, B-scan, and "En-face" SD-OCT were performed in each patient at initial and follow-up visits. Results. Both patients presented with acute onset of blurred vision, and one with bilateral involvement. B-can OCT revealed disruption of the macular retinal pigment epithelial (RPE) inner band layer and photoreceptors' inner and outer segment (IS-OS) junction. Hyperreflective dots were observed in the outer nuclear layer (ONL) above the RPE/IS-OS disruption. Just around these hyperreflective dots, slight thickening of the hyperreflective IS/OS junction was observed. During the late phase, indocyanine green angiography (ICGA) showed a macular cockade-like hyperfluorescent halo. "En-face" OCT showed the same cockade-like appearance with a hyporeflective center and a hyperreflective border matching the pattern observed on ICGA. At followup, as vision improved without treatment, B-scan OCT demonstrated progressive resolution of the hyperreflective and disrupted lesions; "en-face" OCT also showed disappearance of the macular cockade-like halo with a transient discrete hyperreflective macular star at the RPE level in one eye. Conclusion. "En-face" OCT associated with B-scan SD-OCT analysis appears to be very helpful in the diagnosis and followup of ARPE. The pathophysiology of ARPE remains complex and still poorly understood. These techniques help define the location and extent of structural damage occurring in this disease.

Detection of Treponema pallidum in aqueous humor by real-time polymerase chain reaction.

PURPOSE: To report the additional clinical value of real-time Polymerase chain reaction (PCR) in the detection of Treponema pallidum in aqueous humor. METHODS: A real-time (RT) PCR assay targeting the polymerase 1 gene of Treponema pallidum was performed in aqueous humor samples collected in consecutive patients with ocular syphilis. RESULTS: Five patients presenting with optic neuritis (1), posterior placoid chorioretinitis (1), or panuveitis with retinitis (3) were tested. The PCR results were positive in the 3 cases of panuveitis and negative in the 2 other cases. CONCLUSION: RT-PCR for Treponema pallidum in aqueous humor is useful to confirm syphilitic panuveitis.