Use of Fundus Autofluorescence Combined with Optical Coherence Tomography for Diagnose of Geographic Atrophy in Age-Related Macular Degeneration.

The aim of this study was to demonstrate the sensitivity of Optical coherence tomography (OCT) in detection of geographic atrophy (GA) secondary to exudative age related macular degeneration (AMD). In this retrospective case series study 77 patients (53% female, with mean ± standard deviation [SD] of 82.6±9.3 years) with 97 eyes (45 OS [left eyes]/52 OD [right eyes]) were included. This was a retrospective review of the charts of patients who presented with exudative AMD at the Pitié Salpetrière Hospital, Paris, France, between December 2016 and August 2017 that received intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) therapies. At baseline, following biomicroscopy examination, multimodal imaging was performed including, fluorescein angiography (FA), fundus auto-fluorescence (FAF), spectral domain optical coherence tomography (SD-OCT) and indocyanine green angiography (ICGA). During the follow-up, SD-OCT with/without FAF and FA were performed for each patient at 6, 12 and 18 months. For investigation of the prevalence of GA in eyes undergoing intravitreal injections with anti-VEGF therapy, FAF and SD-OCT images were qualitatively reviewed by four independent observers (two graders per group). Kappa coefficient of Cohen was calculated to determine agreement between the graders. The kappa coefficient of Cohen, for inter-rater agreement in the evaluation of FAF images was 0.468, indicating a moderate agreement between the first and second raters. Thus, the sensitivity and specificity of FAF for the diagnosis of GA were 70% and 57%, respectively. If atrophy was assessed with SD-OCT image analysis, the kappa coefficient for inter-rater agreement was 0.846, implying an acceptable agreement between both readers. The sensitivity and specificity of SD-OCT were 93% and 58% respectively. In conclusion, SD-OCT image analysis was more sensitive than FAF for identifying GA in patients treated for exudative AMD.

Reliability and Reproducibility of Pigment Epithelial Detachment Volume Measurements in AMD Using a New Tool: ReVAnalyzer.

BACKGROUND AND OBJECTIVE: To describe and present the reliability and reproducibility of a new software, Retinal Volume Analyzer (ReVAnalyzer), for pigment epithelium detachment (PED) volume quantification. PATIENTS AND METHODS: This is a retrospective study including patients with PEDs secondary to exudative age-related macular degeneration (AMD). Macular volume scans on spectral-domain optical coherence tomography on enhanced depth imaging mode were performed in all eyes. Image batches were then exported in .xml format to the ReVAnalyzer software. A semiautomated PED volume measurement was performed by three independent readers (RBG, VC, OS) twice, at the beginning and end of a 15-day period. Bland-Altman assessment for agreement was used to compare intra- and interobserver observations. RESULTS: Twenty eyes of 20 patients presenting with PED were analyzed. Bland-Altman analysis indicated a good agreement between inter- and intraobserver measurements. The intraclass correlation coefficient for intraobserver PED volume measurements and between the three observers (interobserver) was greater than 0.99, demonstrating high reproducibility and consistency of the methodology. CONCLUSIONS: ReVAnalyzer is a reliable tool that can assist in the analysis of PED volume with high reproducibility. This type of specific retinal volume analysis can be of help for monitoring disease activity and therapeutic response in AMD. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:e242-e249.].

Sensitivity and specificity of optical coherence tomography angiography (OCT-A) for detection of choroidal neovascularization in real-life practice and varying retinal expertise level.

PURPOSE: To evaluate the diagnostic accuracy of OCT angiography (OCT-A) detecting or predicting choroidal neovascularization (CNV), by ophthalmologists of disparate degrees of skills in retinal diseases, using spectral domain optical coherence tomography (SD-OCT) and fluorescein angiography (FA) as a standard reference. METHODS: Retrospective observational case series. Patient presenting maculopathy and complete imaging were included. FA, SD-OCT, OCT-A and FA coupled to SD-OCT images were graded independently for presence or absence of CNV by ophthalmologists with varying expertise levels. RESULTS: Overall sensitivity of OCT-A was 85.62% (95% CI 79.04-90.76%) and specificity was 81.51% (95% CI 73.36-88.03). Sensitivity of FA was 74.51% (95% CI 66.84-81.20), and specificity was 82.35% (95% CI 74.30-88.73). Sensitivity of FA + SD-OCT was 92.72% (95% CI 87.34-96.30), and specificity was 90.91% (95% CI 84.31-95.37). CONCLUSION: OCT-A has good sensitivity and specificity for the detection of CNV in all expertise level groups. OCT-A may soon become a routine tool for CNV diagnosis and follow-up.

Electroretinogram Findings in Early-Stage Sickle Cell Retinopathy According to Hemoglobin Type.

Purpose: Although extensive clinical research has been performed on structural analysis of sickle cell (SC) retinopathy, functional aspects have been poorly investigated. Our purpose was to report full-field electroretinogram (ffERG) findings in patients with early SC retinopathy according to the following hemoglobin types: HbSS or HbSC (homozygous or heterozygous mutations, respectively). Methods: In this monocentric retrospective observational study, patients affected by nonproliferative SC retinopathy were included from November 2014 to April 2016. Patients were separated into one of the following three groups: HbSS, HbSC, and control. All groups underwent full ophthalmologic examination (fundus examination) and ffERG. For SC patients, additional imaging testing was also performed (fluorescein angiography and spectral domain optical coherence tomography). Results: A total of 24 eyes from 12 patients (6 HbSS and 6 HbSC) and 12 eyes from 6 controls were included. The HbSS group exhibited a dramatic decrease of the b-wave amplitudes for all dark-adapted (DA) ffERG responses when compared with the control group (P = 0.02, P = 0.003, P = 0.005, respectively, after DA 0.01, DA 3.0, and DA 10.0 cd.s.m-2 stimulations) and decreased a-wave amplitudes for light-adapted responses (P = 0.03 after light-adapted 3.0 cd.s.m-2 stimulations). The a-Wave amplitudes were significantly reduced for all dark-adapted and light-adapted responses in HbSC group compared to the control group (P = 0.03, P = 0.01, P = 0.03, respectively, after DA 3.0, DA 10.0, and light-adapted 3.0 cd.s.m-2 stimulations). The HbSS+HbSC groups presented decreased a-wave amplitudes for DA and light-adapted responses and decreased b-wave amplitude after DA 0.01 and 10.0 cd.s.m-2 stimulations when compared to the control group. Conclusions: These results could suggest an early involvement of the inner retinal cells in the disease process in HbSS patients and of the outer retinal cells in HbSC patients. This could provide new insights on the pathophysiology of the retinal affection in HbSS/HbSC SC disease.

Macular Microangiopathy in Sickle Cell Disease Using Optical Coherence Tomography Angiography.

PURPOSE: To characterize the optical coherence tomography angiography (OCTA) appearance of the perifoveal macular microvasculature in visually asymptomatic patients with sickle cell disease, and to compare these findings with those of fluorescein angiography (FA). DESIGN: Retrospective observational case series. METHODS: Eighteen eyes of 9 consecutive patients with a median age of 41 years (range: 19-54 years) with electrophoretic confirmation of sickle cell disease were included and analyzed. A complete ophthalmologic examination was performed, including fundus examination, FA, and OCTA. Nine eyes of 5 healthy subjects were also analyzed with OCTA to serve as a control group. RESULTS: OCTA demonstrated microvascular abnormalities in the perifoveal region of the macula in all eyes, whereas FA appeared normal in 9 of 18 eyes (50%). Most capillary abnormalities were located in the temporal juxtafoveal region and involved both the superficial and the deep capillary plexuses. The nonflow area (foveal avascular zone) was significantly larger in sickle cell disease patients than in the control group, both in the superficial and the deep capillary plexuses (P < .0001). The perifoveal vessel density was significantly lower in the sickle cell disease patients than in the control group in both the superficial (P = .0011) and the deep capillary plexuses (P = .0018). CONCLUSION: OCTA provided detailed imaging of the perifoveal microvasculature in sickle cell disease. It appeared more sensitive than FA in detecting macular microangiopathy in asymptomatic patients. Microvascular abnormalities in sickle cell disease involved both the superficial and the deep capillary plexuses.

Optical Coherence Tomography Angiography in Retinal Vein Occlusion: Evaluation of Superficial and Deep Capillary Plexa.

PURPOSE: To evaluate the optical coherence tomography angiography (OCT angiography) appearance of the superficial and deep capillary plexa in eyes with retinal vein occlusion (RVO) and to compare these findings with those of fluorescein angiography (FA) and spectral-domain optical coherence tomography (SD OCT). DESIGN: Retrospective observational case series. METHODS: Patients presenting with RVO to Creteil University Eye Clinic were retrospectively evaluated. All patients had undergone a comprehensive ophthalmic examination including FA, SD OCT, and OCT angiography. RESULTS: There were 54 (31 male, 57%) RVO patients with a mean age of 70 years. The perifoveal capillary arcade was visible in 52 of 54 eyes (96%) on OCT angiography and in 45 eyes (83%) on FA; this arcade was disrupted in 48 eyes (92%) and 39 eyes (72%) on OCT angiography and FA, respectively (P = .002). Perifoveal capillary arcade disruption was correlated with peripheral retinal ischemia (P = .025). Intraretinal cystoid spaces were observed in 34 eyes (68%) using FA, in 40 eyes (76%) using SD OCT, and in 49 eyes (90%) using OCT angiography (P = .008 for OCT angiography vs SD OCT and P = .001 for OCT angiography vs FA). Retinal capillary network abnormalities were observed in all patients in both superficial capillary plexus and deep capillary plexus on OCT angiography. Nonperfusion grayish areas were more frequent in the deep capillary plexus (43 eyes, 84%) than in the superficial capillary plexus (30 eyes, 59%, P < .001). CONCLUSION: OCT angiography can simultaneously evaluate both macular perfusion and edema. For the first time, an imaging technique enables the evaluation of the deep capillary plexus, which appears to be more severely affected than the superficial capillary plexus in RVO.

Spectral-Domain Optical Coherence Tomography of Subretinal Hyperreflective Exudation in Myopic Choroidal Neovascularization.

PURPOSE: To study the effect of anti-vascular endothelial growth factor (VEGF) therapy on subretinal hyperreflective exudation detected by spectral-domain optical coherence tomography (SD OCT) in myopic choroidal neovascularization (CNV). DESIGN: Retrospective consecutive observational cohort study. METHODS: Thirty-one eyes of 31 consecutive highly myopic patients with CNV and showing a subretinal hyperreflective exudation on SD OCT were included. Morphologic changes were assessed before and after anti-VEGF therapy, based on the subretinal hyperreflective exudation thickness, retinal thickness at the level of the CNV, and central macular thickness. RESULTS: After anti-VEGF treatment (mean follow-up of 1.9 ± 0.8 months, mean number of injections 1.8 ± 0.6), the subretinal hyperreflective exudation regressed completely in 29 of 31 eyes (93.5%) and partially in 2 of 31 eyes (6.5%). Mean subretinal hyperreflective exudation thickness, mean retinal thickness at the level of the CNV, and mean central macular thickness significantly decreased from 102 ± 50 µm to 2.6 ± 10.2 µm (P < .0001), from 419 ± 99 µm to 312 ± 64 µm (P < .0001), and from 361 ± 69 µm to 326 ± 72 µm (P = .0008), respectively. CONCLUSION: The subretinal hyperreflective exudation was an SD OCT finding that correlated with signs of active myopic CNV (either subretinal fluid/intraretinal cysts on SD OCT or dye leakage on fluorescein angiography) and responded to treatment with anti-VEGF agents. The presence of a subretinal hyperreflective exudation on SD OCT could help in making decisions on the need to perform or not perform fluorescein angiography, and regarding treatment or retreatment.

Intraocular pressure after intravitreal injection of dexamethasone implant for macular edema resulting from retinal vein occlusion.

PURPOSE: A recognized side effect of corticosteroids intravitreal injections (IVT) is the onset of ocular hypertension. The aim of our study was to analyze changes in short-term intraocular pressure (IOP) after IVT of sustained-release dexamethasone implant in order to provide an appropriate monitoring scheme. METHODS: In this retrospective study, the charts of 44 eyes of 42 patients treated by IVT of dexamethasone implant for macular edema resulting from retinal vein occlusion were reviewed. The IOP measurements were performed at baseline and at 15 minutes, 7 days (D7), 1 month (M1), 2 months (M2), and 4 months (M4) after IVT. RESULTS: Mean IOP was 13.4 ± 2.5 mm Hg at baseline. Twelve eyes out of 44 (27.3%) were treated with antihypertensive eyedrops for a well-controlled glaucoma at baseline. Following IVT, mean IOP was 11.5 ± 3.6 mm Hg at 15 minutes, 14.7 ± 3.1 mm Hg at D7, 16.4 ± 7.0 mm Hg at M1, 19.3 ± 7.9 mm Hg at M2, and 13.5 ± 3.1 mm Hg at M4. An IOP ≥25 mm Hg or increased by 10 mm Hg or more was not observed in any eye at 15 minutes, D7, or M4 after IVT, but in 8.6% of cases at M1 and in 25% at M2. CONCLUSIONS: It seems reasonable to perform the first IOP monitoring 1 month after IVT of dexamethasone implant and at each efficacy assessment visit (M2, M4). Special attention should be given to patients at risk, such as glaucoma patients. An IOP measurement immediately after IVT and in the following days (1 week) does not seem to be appropriate on a routine basis.

In vivo visualization of perforating vessels and focal scleral ectasia in pathological myopia.

PURPOSE: To describe focal scleral ectasia in areas of macular/perimacular patchy chorioretinal atrophy secondary to pathologic myopia. METHODS: Thirty-nine consecutive patients with pathologic myopia and chorioretinal atrophy in at least one eye, with and without focal scleral ectasia, were analyzed by infrared reflectance (IR) and/or multicolor imaging, enhanced depth imaging optical coherence tomography (EDI-OCT) (39 patients, 78 eyes), and swept source (SS)-OCT (13 out of 39 patients, 26 eyes) cross-sectional scan. RESULTS: Focal scleral ectasia was found in 12 out of 68 eyes (11 out of 39 consecutive patients, 27 females/12 males; mean age 65.7 ± 11.9 years) with macular/perimacular patchy chorioretinal atrophy, and was always observed inferior or temporal to the macula (mean 1.25 ± 0.38/eye). Focal scleral ectasia, appearing on fundus examination as a deep dark round/oval lesion with well-defined borders, was characterized on EDI-OCT and SS-OCT by an abrupt posterior bow of the sclera with different degrees of scleral schisis on its borders. The retinal pigment epithelium and the choroid were absent in all lesions. IR reflectance and multicolor imaging showed large vessels that seem to emerge from the focal scleral ectasia, and crossing the area of patchy atrophy. EDI-OCT and SS-OCT revealed retrobulbar vessels perforating the sclera at the borders/bottom of the abrupt posterior bow of the sclera (i.e., focal scleral ectasia) and running through the superficial scleral thickness for the whole extension of the atrophic area. CONCLUSIONS: We showed that perforating vessels are localized at the border/bottom of focal scleral ectasia in pathologic myopia.

Morphologic characterization of dome-shaped macula in myopic eyes with serous macular detachment.

PURPOSE: To analyze dome-shaped maculas topographic features and related serous retinal detachment (SRD) in eyes with myopic staphyloma. DESIGN: Retrospective, observational case series. METHODS: We reviewed the records of 48 eyes in 33 patients with dome-shaped maculas who were referred because of decreased vision. Ophthalmologic examination included axial length measurement, spectral domain optical coherence tomography (OCT), and fluorescein and indocyanine green angiography. The height of the macular bulge was measured, and the choroidal thickness was mapped. RESULTS: Patient mean age was 55.0 ± 13.6 years. Mean axial length was 27.49 ± 2.53 mm. Mean best-corrected visual acuity (BCVA) was 0.50 ± 0.33 logMAR. Three dome-shaped macula patterns were observed: round dome in 10/48 (20.8%) eyes; horizontal oval-shaped dome in 30/48 (62.5%) eyes; and vertical oval-shaped dome in 8/48 (16.7%) eyes. The mean macular bulge height was 407.7 ± 215.1 µm (120-1130) and was significantly greater in vertical oval-shaped domes. The mean central choroidal thickness (CCT) was 146.5 ± 56.0 µm, significantly greater than at 3 mm nasal and temporal to the fovea (P < 0.0001). The CCT was positively correlated to macular bulge height but not to BCVA. Foveal SRD was present in 25/48 eyes and significantly increased for macular bulge height greater than 350 µm (P = 0.0047). BCVA was significantly lower when SRD was present (P = 0.043). CONCLUSIONS: Most dome-shaped maculas did not display a round but a horizontal or vertical oval-shaped dome and could be missed on a single OCT scan. Chronic foveal SRD was associated with decreased vision and was more common when the macular bulge was highly elevated.

Ranibizumab for choroidal neovascularization associated with adult-onset foveomacular vitelliform dystrophy: one-year results.

PURPOSE: To evaluate the efficacy of intravitreal injections of ranibizumab for choroidal neovascularization associated with adult-onset foveomacular vitelliform dystrophy. METHODS: Retrospective case series of 24 eyes affected with choroidal neovascularization associated with adult-onset foveomacular vitelliform dystrophy treated by intravitreal injections of ranibizumab (0.5 mg/0.05 mL). Best-corrected visual acuity, fundus examination, spectral domain optical coherence tomography, fundus autofluorescence, and fluorescein and indocyanine green angiography were performed for the diagnosis of adult-onset foveomacular vitelliform dystrophy and choroidal neovascularization. After initial 3 monthly injections of ranibizumab, patients were followed up monthly and retreated if neovascular activity persisted. Outcome measure was the proportion of patients losing fewer than 3 lines of visual acuity from baseline to 12 months (final visit). RESULTS: At final visit, the mean number of ranibizumab injections was 4.5 ± 1.29. From baseline to final visit, 21 of 24 eyes (87.5%) lost fewer than 3 lines of visual acuity. Mean best-corrected visual acuity did not change significantly from baseline to final visit (0.37 ± 0.2 logarithm of the minimum angle of resolution vs. 0.30 ± 0.25 logarithm of the minimum angle of resolution, respectively; P = 0.115). Mean central macular thickness significantly decreased from baseline to final visit (327 ± 83 µm vs. 260 ± 57 µm, respectively; P = 0.001). CONCLUSION: In this series, ranibizumab succeeded in stabilizing best-corrected visual acuity in patients with choroidal neovascularization associated with adult-onset foveomacular vitelliform dystrophy. Ranibizumab seems to be a reasonable therapeutic option in this condition.

Angiographic and optical coherence tomography characteristics of recent myopic choroidal neovascularization.

PURPOSE: To analyze the contribution of fluorescein angiography (FA) and spectral-domain optical coherence tomography (SD OCT) to the diagnosis of recent choroidal neovascularization (CNV) associated with high myopia. DESIGN: Retrospective, observational case series. METHODS: Ninety eyes of 73 highly myopic patients (refractive error ≥-6 diopters) with CNV in 1 or both eyes were included. Epidemiologic features, refractive error, fundus examination, fluorescein angiography, and SD OCT findings at onset of CNV were analyzed. RESULTS: Mean age at onset of CNV was 54.4 ± 14 years. CNV was bilateral in 17 of 73 cases. Mean refractive error was -13.9 ± 5.2 diopters. Myopic CNV was associated more frequently with patchy or geographic atrophy (P = .019). CNV was associated with exudative features on fluorescein angiography in 82% of cases (64/78), and on SD OCT in 48.6% of cases (36/74). There was no agreement about signs of active CNV between these 2 imaging methods (κ = 25.7 ± 10%; P = .0044). CNV area was significantly smaller in younger patients (<55 years) than in older patients (0.57 mm(2) vs 1.21 mm(2), respectively; P = .023). CONCLUSIONS: Exudative features of myopic CNV are more obvious on FA than on SD OCT, suggesting that fluorescein angiography should be performed when new-onset myopic CNV is suspected. Myopic CNV occurring in older patients (≥55 years) is larger than those seen in younger patients and resembles CNV associated with age-related macular degeneration. This suggests an overlap between myopic CNV in older patients and age-related macular degeneration.

Bilateral macular serous retinal detachment revealing acute myeloblastic leukemia.

PURPOSE: To report a case of bilateral serous retinal detachment revealing acute myeloblastic leukemia. METHODS: A 31-year-old man presenting with decreased vision in both eyes, 20/50 in the right eye and 20/32 in the left eye, was submitted to a complete ophthalmologic and systemic evaluation. RESULTS: Fundus biomicroscopy, fluorescein and indocyanine green angiography, and spectral domain optical coherence tomography showed bilateral serous retinal detachment and signs of choroidal ischemia. Enhanced depth imaging spectral domain optical coherence tomography allowed a precise examination of the choroid, by showing an overall thickening of the choroid (749 µm in the right eye and 728 µm in the left eye) and disappearance of the normal hyporeflective visualization of the choroidal vessels. On systemic investigation, the patient was diagnosed with acute myeloblastic leukemia. After systemic chemotherapy, visual acuity improved to 20/20 in both eyes, with resolution of the bilateral serous retinal detachment and choroidal changes. CONCLUSION: Bilateral serous retinal detachment may be a presenting sign of acute myeloblastic leukemia. Examination of the choroid using enhanced depth imaging spectral domain optical coherence tomography may suggest the etiology and contribute to early diagnosis and treatment.

Genetic factors for choroidal neovascularization associated with high myopia.

PURPOSE: Nonsyndromic high myopia, defined by a refractive error greater than -6 diopters (D), is associated with an increased risk of macular choroidal neovascularization (CNV), a vision-threatening complication. The aim of this study was to investigate whether genetic factors associated with age-related macular degeneration (AMD) are related to myopic CNV. METHODS: We conducted a case-control study, including 71 cases with myopic CNV and 196 myopic controls without CNV, from Creteil and Toulouse, France, and Boston, MA. Single nucleotide polymorphisms (SNPs) from 15 genes reported to be related to AMD were selected for association testing in this study. RESULTS: In univariate analysis, the rs10033900 SNP located in CFI was associated with myopic CNV (P = 0.0011), and a SNP in APOE was also related (P = 0.041). After adjustment for age, sex, and degree of myopia, SNPs in three genes were significantly associated, including CFI (odds ratio [OR] 2.1, 95% confidence interval [CI] 1.3-3.37, P = 0.0023), COL8A1 (OR 1.88, 95% CI 1.18-2.98, P = 0.0076), and CFH (OR 1.65, 95% CI 1.02-2.66, P = 0.04). After correction for multiple testing, only CFI remained significantly related to high myopic CNV (P = 0.045). CONCLUSIONS: We report the first genetic associations with choroidal neovascularization (CNV) in a high myopic Caucasian population. One SNP (rs10033900) in the CFI gene, which encodes a protein involved in the inflammatory pathway, was significantly associated with myopic CNV in multivariate analysis after correction for multiple testing. This SNP is a plausible biological marker associated with CNV outgrowth among high myopic patients. Results generate hypotheses about potential loci related to CNV in high myopia, and larger studies are needed to expand on these findings.