Areas Of Retinal Pigment Epithelium Atrophy Research Articles

Multimodal Retinal Imaging Reveals New Pathogenic Insights in Central Areolar Choroidal Dystrophy: A Case Series.

To describe novel imaging findings in a family affected by central areolar choroidal dystrophy (CACD). Case series with multimodal retinal imaging assessment. A 19-year-old asymptomatic woman was referred for bilateral macular defects of the retinal pigment epithelium (RPE). Blue-light autofluorescence (BAF) of her right eye revealed a speckled pattern in the macular area with a ring of decreased autofluorescence using near-infrared autofluorescence (NIR-AF). Multimodal assessment of her left eye disclosed a single parafoveal spot of decreased pigmentation that was clearly visible as hyper-autofluorescent using BAF and as hypo-autofluorescent using NIR-AF. Optical coherence tomography angiography (OCT-A) revealed several tiny areas of flow voids in correspondence of the RPE alterations of both eyes.Three family members were recently diagnosed with presumed age-related macular degeneration and demonstrated well-demarcated areas of RPE atrophy surrounded by yellowish deposits and a hypo-pigmented halo.Next-generation genetic analysis for inherited macular dystrophies was performed on the index case and the affected family members and revealed a p.Arg172Gln missense mutation in PRPH2 gene, leading to the diagnosis of CACD. Multimodal imaging can reveal new pathogenic insights in CACD. Of notice, NIR-AF and OCT-A are able to detect RPE hypopigmentation and choriocapillaris rarefaction, respectively, since the earliest stages of the disease.

Morphometric Risk Factors for Drusenoid Pigment Epithelium Detachment Collapse and Retinal Pigment Epithelium Atrophy Expansion.

The purpose of this study was to investigate factors associated with drusenoid pigment epithelium detachment (dPED) growth rate, incidence of dPED collapse, and retinal pigment epithelium (RPE) atrophy enlargement rate following dPED collapse and their impact on visual acuity (VA). This was a retrospective longitudinal study on 44 eyes. Serial spectral-domain optical coherence tomography (SD-OCT) and fundus autofluorescence (AF) imaging were performed. Qualitative features and quantitative dPED-related metrics were assessed. The surface-to-volume ratio (S/V) was computed to evaluate dPED shape irregularity. AF imaging was utilized to measure RPE atrophy area in eyes experiencing dPED collapse. Regression models were used to analyze associations among VA, dPED growth rate, and RPE atrophy enlargement rate. Cox regression was used to identify risk factors for dPED collapse. Significant correlations were observed between dPED area, surface, and volume (P < 0.05 for all pairs). The dPED metrics were inversely correlated with the S/V. Incidence of dPED collapse was 22 per 100 eye-years over a mean follow-up of 59 ± 41 months. Eyes experiencing collapsed dPED had worse baseline VA (P < 0.001). RPE hypertransmission (hazard ratio [HR] = 3.68, P = 0.004) and hyper-reflective foci (HR = 3.45, P = 0.02) were risk factors for dPED collapse; a higher S/V ratio was protective (HR = 0.78, P = 0.03). A faster rate of RPE atrophy enlargement was associated with a faster rate of dPED volume increase (r = 0.47, P = 0.02) and worse VA over time (P = 0.02). Risk stratification in patients with dPED can be aided by identifying risk factors for dPED collapse. Identifying factors associated with RPE atrophy enlargement may have implications for treatment decision making.

Progression of Pentosan Polysulfate Sodium Maculopathy in a Prospective Cohort

To describe the progression of pentosan polysulfate sodium (PPS) maculopathy after drug discontinuation qualitatively and quantitatively using multimodal imaging assessmen. Prospective case series. Patients with PPS maculopathy were evaluated after discontinuation of PPS. Near-infrared reflectance (NIR), fundus autofluorescence (FAF), and optical coherence tomography (OCT) were evaluated in all patients at baseline and at the final follow-up visit at least 12 months later. A qualitative and quantitative analysis of the retinal imaging findings was performed. Patterns of disease progression were evaluated. Area of disease involvement on FAF, retinal pigment epithelium (RPE) atrophy on FAF and NIR, and retinal layer thicknesses on OCT were measured at baseline and at the follow-up visit. A total of 26 eyes were included, with a follow-up period ranging from 13 to 30 months. The diseased area measured on FAF showed significant expansion in all eyes from baseline to follow-up despite drug cessation (P=.03) with a median linearized rate of change of 0.42 mm/y. There was significant reduction in the central macular thickness (P=.04), inner nuclear layer thickness (P=.003), outer nuclear layer thickness (P=.02), and subfoveal choroidal thickness (P=.003) at follow-up vs baseline. New areas of RPE atrophy on FAF in the macula developed in 4 eyes while preexisting atrophic lesions increased in size in 5 eyes. Eyes with baseline PPS maculopathy all exhibited remarkable progression with qualitative and quantitative multimodal imaging analysis despite drug discontinuation. Disease progression may be attributed to underlying inner choroidal ischemia or RPE impairment.

Optical coherence tomography angiography in Bietti crystalline dystrophy.

Bietti crystalline dystrophy (BCD) is a rare autosomal recessive retinal dystrophy caused by pathogenic variants of CYP4V2 gene and characterized by shiny yellow deposits in the retina and progressive atrophy of the retinal pigment epithelium (RPE) and choriocapillaris. The main aim of the present study is to describe the optical coherence tomography angiography (OCTA) characteristics of a patient affected by BCD. A 59-years-old female with genetically confirmed BCD underwent an ophthalmological examination complete of OCTA performed in the atrophic retina, the junctional zone and the apparently normal retina. The area of choriocapillaris (CC) atrophy was compared to the area of RPE atrophy on fundus autofluorescence (FAF) imaging. A severe vessel density (VD) deficit at the level of superficial and deep capillary plexa as well as CC was registered in atrophic areas, which resulted deeper with respect to the junctional area, whereas the apparently preserved retina revealed VD values similar to that of control eyes. The area of RPE atrophy on FAF was larger (55.90 mm2 in right eye and 48.76 mm2 in left eye) than the area of CC atrophy on OCTA imaging (51.86 mm2 and 42.44 mm2 respectively in right and left eye). Our findings suggest that VD impairment of retinal plexa and CC follows the degeneration of RPE as demonstrated by the greater size of the area of RPE atrophy compared to CC atrophy. Further investigations based on OCTA imaging are necessary to enhance our knowledge of this rare disease.

Outer nuclear layer relevance in visual function correlated to quantitative enface OCT parameters in Stargardt disease.

To evaluate the correlation between Best Corrected Visual Acuity (BCVA) and the following parameters in Stargardt Disease (STGD): Central Retinal Thickness (CR-T), Central Outer Nuclear Layer Thickness (C-ONL-T), Areas of macular Photoreceptor loss (PHRa), and Retinal Pigment Epithelium (RPE) loss (RPEa). A total of 64 eyes of 32 STGD patients were included in the study. All patients received a comprehensive ophthalmological examination, color fundus photographs, fundus auto-fluorescence imaging, and Optical Coherence Tomography (OCT). The CR-T and C-ONL-T were evaluated from standard SD-OCT scans. The PHRa and RPEa were calculated from enface OCT scans (sub RPE slab and photoreceptor slab). The collected OCT parameters were evaluated for possible association with BCVA. The mean macular PHRa and RPEa was 16.16 ± 13.36 and 12.05 ± 12.57 mm2 respectively. The mean CR-T measured 120.78 ± 41.49 μm while the mean C-ONL-T was assessed at 4.60 ± 13.73 μm. BCVA showed the highest correlation with the C-ONL-T (r = -0.72; p < 0.001) while there was no correlation with the CR-T (r = -0.17; p = 1.00). Enface OCT permits a rapid and precise quantitative evaluation of the macular PHR and RPE atrophy area in STGD. Nonetheless, the OCT parameter that showed the highest correlation with visual acuity in STGD was the ONL thickness.

Retinal Pigment Epithelium Atrophy in Recessive Stargardt Disease as Measured by Short-Wavelength and Near-Infrared Autofluorescence.

PurposeTo compare the detection of retinal pigment epithelium (RPE) atrophy in short-wavelength (SW-AF) and near-infrared autofluorescence (NIR-AF) images in Stargardt disease (STGD1) patients.MethodsSW-AF and NIR-AF images (115 eyes from 115 patients) were analyzed by two independent graders. Hypoautofluorescent (hypoAF) areas, indicative of RPE atrophy, were measured, and the two modalities were compared.ResultsPatients were segregated into four groups: nascent (6 [5%]), widespread (21 [18%]), discrete (55 [48%]), and chorioretinal atrophy (33 [29%]). The areas of hypoAF were larger in NIR-AF compared to SW-AF images in discrete (3.9 vs. 2.2 mm2, P < 0.001) and chorioretinal atrophy (12.7 vs. 11.4 mm2, P = 0.015). Similar findings were observed qualitatively in nascent and widespread atrophy patients. Using the area linear model (ALM), lesion area increased at similar rates in SW-AF and NIR-AF images of discrete atrophy (0.20 vs. 0.32 mm2/y, P = 0.275) and chorioretinal atrophy (1.30 vs. 1.74 mm2/y, P = 0.671). Using the radius linear model (RLM), the lesion effective radius also increased similarly in SW-AF and NIR-AF images in discrete (0.03 vs. 0.05 mm2/y, P = 0.221) and chorioretinal atrophy (0.08 vs. 0.10 mm2/y, P = 0.754) patients.ConclusionsNIR-AF reveals a larger area of RPE atrophy in STGD1 patients compared to SW-AF images, but rates of lesion enlargement in the two modalities are similar.Translational RelevanceMeasurements of RPE atrophy by AF imaging are crucial for monitoring STGD1 disease progression and given our findings we advocate greater use of NIR-AF for patients.

Retinal pigment epithelial tear in age-related macular degeneration

Retinal pigment epithelial tear (RPET) occurs in a number of diseases, most often in age-related macular degeneration (AMD). RPET develops in the setting of retinal pigment epithelium (RPE) detachment and represents a violation of the integrity of its monolayer accompanied by the formation of a demarcation line between the RPE atrophy area and RPE folds. Its incidence varies widely. In the earlier studies, diagnosis of RPET was performed using fluorescent angiography or angiography with indocyanine green (ICG-FA). The advent of optical coherence tomography made the detection of RPET easier and more accessible. The mechanism of RPET formation is quite polymorphic and ambiguous. Scientific literature contains descriptions of the occurrence of RPET when using both ranibizumab and aflibercept, and bevacizumab in equal proportions, implying that the drug choice does not affect the occurrence of complications. Continuous monitoring and adherence to anti-VEGF therapy leads to better anatomical and functional results in the long term, which is crucial for improving the quality of life of patients with age-related macular degeneration. This article reviews the literature and presents current data on RPET, identifies risk factors and mechanisms of its development, provides classification, and describes modern options for its diagnosis and treatment.

Fluorescence Lifetime Patterns of Retinal Pigment Epithelium Atrophy in Patients with Stargardt Disease and Age-Related Macular Degeneration

Purpose: To investigate whether autofluorescence lifetime patterns within retinal pigment epithelium (RPE) atrophy differ between age-related macular degeneration (AMD) and Stargardt disease (STGD). Methods: Mean retinal autofluorescence lifetimes were measured in a short and a long spectral channel (SSC: 498–560 nm; LSC: 560–720 nm). Mean retinal fluorescence lifetimes were analyzed with corresponding clinical features, fundus images, fundus autofluorescence intensity images, and optical coherence tomography. Mean fluorescence lifetime values of atrophic areas were compared between the two cohorts and within the same patient to adjacent nonatrophic regions. Results: Mean fluorescence lifetimes within areas with RPE atrophy of 13 patients with STGD (mean age ± SEM 43.7 ± 5 years) and 30 patients with geographic atrophy (mean age: 78 ± 2 years) were analyzed and compared to age-matched healthy participants. The mean area of RPE atrophy in STGD and AMD was 6.6 ± 2.3 mm² (range: 0.66–33.17 mm²) and 17.5 ± 3.8 mm² (range: 0.58–50.02 mm²), respectively. In patients with AMD, atrophic areas revealed significantly longer mean fluorescence lifetime values as compared with patients with STGD (SSC: 997 ± 60 vs. 363 ± 26 ps; LSC: 880 ± 46 vs. 393 ± 23 ps; p < 0.0001). Conclusions: This study established that RPE atrophy in patients secondary to STGD and AMD display distinctive mean fluorescence lifetime characteristics. As retinal fluorescence lifetimes within areas of RPE atrophy were significantly longer in AMD patients, the analysis of specific lifetime patterns may provide additional insight into the disease processes and the pathogenetic mechanisms in the development of atrophic patches in AMD and STGD.

Retinal sensitivity in angioid streaks

To investigate retinal sensitivity in eyes with angioid streaks (AS). This study was a retrospective observational case series. A total of 13 eyes from 9 patients with AS underwent ophthalmologic examination, including fundus autofluorescence (FAF), spectral domain optical tomography (SD-OCT), and microperimetry. Retinal pigment epithelium (RPE) atrophy was assessed using FAF. Outer retinal atrophy, more specifically, disruption of the ellipsoid zone, was evaluated using SD-OCT images. The association between retinal sensitivity, RPE atrophy or outer retinal atrophy, and patient demographic characteristics or ophthalmologic findings were investigated. The mean area of outer retinal atrophy was 14.5 ± 12.9mm2, significantly larger than the mean area of RPE atrophy (9.0 ± 9.0mm2; P = 0.0028). The average retinal sensitivity in the area of RPE atrophy was 2.4 ± 5.6dB, that in the area of outer retinal atrophy outside RPE atrophy was 14.6 ± 7.5dB, and that in the area without any atrophy was 25.6 ± 5.1dB. Reticular pseudodrusen (RPD) was observed in 5 eyes. Eyes with RPD showed a greater extent of both outer retinal atrophy and RPE atrophy than those without RPD and a greater decrease in mean retinal sensitivity. In eyes with AS, especially in those with RPD, large areas of outer retinal atrophy and RPE atrophy were observed, and the retinal sensitivity in the areas was correspondingly decreased.

Correlation of Outer Retinal Degeneration and Choriocapillaris Loss in Stargardt Disease Using En Face Optical Coherence Tomography and Optical Coherence Tomography Angiography

This study measured and correlated degeneration of the junction between the inner and outer segments (IS/OS), the retinal pigment epithelium (RPE), and the choriocapillaris (CC) in Stargardt disease (STGD). Prospective cross-sectional study. This study was conducted at the Casey Eye Institute. A total of 23 patients with STGD were enrolled and underwent optical coherence tomography angiography (OCTA). Scans were centered on the fovea. OCT slab projections and en face boundary maps were used to create masks to measure total IS/OS loss or RPE atrophy as well as regions of isolated IS/OS loss, isolated RPE atrophy, and matched IS/OS and RPE degeneration or intact IS/OS junction and RPE. CC vascular density (CCVD) was quantified from the CC angiogram. Outcomesincluded the area of loss, and the CCVD of degeneration in different areas was quantified and correlated. The total area of IS/OS loss was strongly correlated with the total area of RPE atrophy (r=0.96; P < 0.0001) by a 1.6:1 ratio (r2= 0.90). CCVD within regions of matched degeneration (85.6% ± 2.7%; P < 0.0001), isolated IS/OS junction loss (93.6% ± 1.0%; P= 0.0011), and isolated RPE atrophy (94.1% ± 1.1%; P= 0.0065) were all significantly lower than normal (99.0% ± 0.17%). There was a trend for CCVD within intact areas (97.6% ± 0.38%) to decline as the area diminished (r= 0.68). Photoreceptor and RPE degeneration exhibited a strong relationship wherein the IS/OS loss was 1.6-fold greater than that of RPE atrophy, supporting the theory that photoreceptor degeneration precedes RPE in STGD. Both the photoreceptors and the RPE degeneration contributed synergistically to CCVD attenuation, but extralesional CCVD also tended to be abnormal. The findings and techniques in this study may be of utility in developing endpoints for clinical trials.

OCT Angiography of the Choriocapillaris in Central Serous Chorioretinopathy: A Quantitative Subgroup Analysis.

IntroductionTo quantify optical coherence tomography angiography (OCTA) signal changes at the level of the choriocapillaris (CC) in patients with different stages of central serous chorioretinopathy (CSC) and to explore any correlation between subretinal fluid (SRF) and retinal pigment epithelium (RPE) alterations and the OCTA CC signal.MethodsOne hundred one CSC eyes and 42 healthy control eyes were included in this retrospective study. CSC patients were allocated into four groups: acute, non-resolving, chronic atrophic and inactive CSC. CC OCTA images (AngioPlex®, Zeiss) were automatically quantified using an image-processing algorithm. Spatial correlation analysis of OCTA signals was performed by overlapping macular edema heatmaps and fundus autofluorescence images with corresponding OCTA images.ResultsActive CSC subgroups demonstrated significantly more increased and decreased flow pixels in the CC compared with controls (p < 0.0001). No significant OCTA changes were seen within the active CSC groups or between the inactive and healthy subgroup. Spatial correlation analysis revealed a decreased OCTA signal in the SRF area and an increased signal outside the SRF area in acute CSC. Areas of RPE atrophy co-localized with areas of increased choriocapillaris OCTA signal, while areas with RPE alterations exhibited a normal signal compared with unaffected RPE.ConclusionThe decreased OCTA signal in the area of SRF in acute CSC could be evidence of localized CC hypoperfusion or due to shadowing artifacts. The missing CC OCTA changes in altered RPE adjacent to atrophy argues against CC injury. Studies with higher resolution and optimized image acquisition are warranted to further validate our findings.Electronic supplementary materialThe online version of this article (10.1007/s40123-018-0159-1) contains supplementary material, which is available to authorized users.

New Insights Into the Development and Progression of Geographic Atrophy After Full Thickness Autologous Choroidal Graft.

To investigate if the contiguity between native and transplanted retinal pigment epithelium (RPE) represents a protective factor against the progression of atrophy after autologous choroidal graft. In addition, the changes in fundus autofluorescence (FAF) in the contiguous and noncontiguous RPE areas were explored. The first postoperative reliable FAF image was selected and divided into sectors based on the characteristics of the RPE at the edge of the graft. The sectors were categorized into three groups: contiguous RPE, noncontiguous RPE, and not classifiable. The area of RPE atrophy, inside and outside the graft, was measured for each sector at baseline, one, three, and five years of follow-up. The FAF pattern outside the graft was evaluated for every sector at baseline and during the follow-up. Nineteen patients met the inclusion criteria and were included in this study. Trend analysis showed that the atrophy progression outside the graft was statistically significant in areas where native and transplanted RPE were noncontiguous (P < 0.0001) yet not so in contiguous areas (P < 0.058). Inside the graft, both groups showed an increase in atrophy over time. In addition, the noncontiguous group developed more severe increased FAF patterns compared with the contiguous group. RPE contiguity after autologous choroidal graft seems to be a protective factor against atrophy progression, whereas any area of damaged or absent RPE tends to enlarge over time. This may suggest that the transplantation of an RPE sheet is more likely to be effective than an RPE cell suspension.

Fundus Autofluorescence Lifetime Patterns in Retinitis Pigmentosa.

We investigated whether fundus autofluorescence (FAF) lifetimes in patients with retinitis pigmentosa display a disease-specific lifetime pattern. Fundus autofluorescence lifetime imaging ophthalmoscopy (FLIO) was performed in two spectral channels (498-560 and 560-720 nm) after excitation with a 473 nm pulsed laser in patients with retinitis pigmentosa and compared to healthy controls of a similar age range. Corresponding FAF intensity and spectral domain optical coherence tomography (OCT) data, as well as best corrected visual acuity (BCVA) were acquired and compared to fluorescence lifetime data. We investigated 43 eyes from 43 patients with retinitis pigmentosa (mean age 45 ± 15 years) and compared them to eyes of 13 age-matched healthy participants. Mean FAF lifetimes were prolonged in areas of photoreceptor atrophy with preserved retinal pigment epithelium (RPE) (P = 0.0036) and even longer in areas with total atrophy of photoreceptors and RPE (P = 0.0002). The prevalence of perifoveal ring structures characterized by prolonged fluorescence lifetimes in FLIO was higher (63% vs. 49%) and the rings were wider compared to the hyperautofluorescent rings in qualitative fundus autofluorescence intensity images. In the central fovea with intact retinal layer structure identified by OCT, fluorescence lifetimes were slightly prolonged compared to those of age-matched healthy controls (short spectral channel [SSC], P = 0.0044; long spectral channel [LSC], P = 0.0128). Short lifetimes within the macular center were negatively correlated with BCVA (R2 = 0.33, P < 0.0001) as well as the greatest diameter of the ellipsoid band in OCT. FLIO in retinitis pigmentosa reveals characteristic patterns that allow identification of areas of photoreceptor atrophy, RPE atrophy, and remaining photoreceptor segments in areas of RPE atrophy. Fluorescence lifetimes can be used to identify ellipsoid zone loss that correlates with functional parameters.

Visual Cortex Activation in Patients With Stargardt Disease.

Primary visual cortex (PVC) contains a retinotopic map in which the central visual field (CVF) is highly magnified compared to the peripheral field. Several studies have used functional magnetic resonance imaging (fMRI) in patients with macular degeneration to assess the reorganization of visual processing in relationship with the development of extrafoveal preferred retinal locus (PRL). We evaluated the functional response in PVC and its correlation with retinal parameters in patients with Stargardt disease due to ABCA4 mutations (STGD1). Twenty-four STGD1 patients underwent best-corrected visual acuity, full-field standard electroretinogram (ERG), optical coherence tomography, and microperimetry. Furthermore, patients underwent fMRI to assess cerebral activation during visual stimulation by a flickering checkerboard in four PVC subdivisions, corresponding to 0° to 5° (V1), 5° to 10° (V2), 10° to 15° (V3), and 15° to 40° (V4) of CVF. Higher ERG responses were significantly (P < 0.0125) associated with larger functional cerebral response in V1, V2, and V3 subdivisions. Moreover, larger retinal pigment epithelium atrophy area was significantly (P < 0.0125) associated with smaller PVC activation in V2 and V3 subdivisions. Larger activation in V1 subdivision was significantly (P = 0.001) associated with higher mean macular sensitivity and smaller dense scotoma size. Finally, our results showed reduced activation in V2 and V3 with increased PRL eccentricity. Our study, for the first time in the literature, showed stronger PVC activation in STGD1 patients with a more preserved retinal function and macular structure. Furthermore, our study data strongly suggest that the evaluation of neuronal reorganization could be performed by considering only retinal parameters, particularly ERG responses.

Progression of Retinal Pigment Epithelium Atrophy in Patients with Long-Term Anti-Vegf Treatment for Exudative Age-Related Macular Degeneration

Abstract Introduction.Age-related macular degeneration is the leading cause of visual impairment in developed world. The reason for using intravitreal injections of anti-vascular endothelial growth factor (VEGF) is to prevent choroidal neovascularization which is the main pathogenic mechanism for exudative age-related macular degeneration. Although injections may improve visual acuity, there are evidence showing association of anti-VEGF injections with progression of retinal pigment epithelium (RPE) atrophy. Aim of the Study.The purpose of this study was to investigate the intravitreal anti-vascular endothelial growth factor impact on retinal pigment epithelium atrophy development and progression. Material and methods.A single-centre retrospective study was conducted. Total 51 eyes of 39 patients with exudative age-related macular degeneration undergoing intravitreal anti-vascular endothelial growth factor therapy for 48 months. Heidelberg Spectralis Optical Coherence Tomography and fundus autofluorescence were used for evaluation of retinal pigment epithelium atrophy area and retinal thickness. Measurements were made manually. Best-corrected visual acuity (BCVA) measurements were taken from patient medical histories. For statistical analysis, IBM Statistical Package for the Social Sciences, version 23.0 was used. Results.The average age of patients was 81.6 ± 6.7 years. After first year of intravitreal anti-VEGF therapy, retinal pigment epithelium atrophy area enlarged from baseline (from 1.91 ± 2.3 mm2 to 2.74 ± 2.3mm2, p &lt; 0.001). The mean number of intravitreal anti- VEGF injections received in 48 months was 15.47 ± 5.14. There was a statistically significant correlation between total number of intravitreal injections and RPE atrophy (R = 0.757, p &lt; 0.001). After first year of anti-VEGF therapy best-corrected visual acuity (decimals) was statistically improved from baseline (0.32 ± 0.26 to 0.37 ± 0.24, p = 0.04). However, despite significant improvement at first year, the further treatment contributed BCVA reduction. Conclusions.Retinal pigment epithelium atrophy is a frequent finding in eyes with exudative age-related macular degeneration before and after anti-VEGF therapy. Our data show statistically significant association between total number of intravitreal anti-VEGF injections and retinal pigment epithelium atrophy area enlargement. Also there was statistically significant best-corrected visual acuity improvement after first year of anti-VEGF therapy.

Influence of repetitive intravitreal ranibizumab for neovascular age-related macular degeneration on retinal pigment epithelium and choroidal thickness

Background Intravitreal injection of ranibizumab (IVR) is one of the most effective therapies for neovascular age-related macular degeneration (nAMD). Understanding the influence of IVR on retinal pigment epithelium (RPE) and choroidal thickness is helpful for us to choose the operative times and timing based on pharmacologic effects and tissue response.However, limited studies are available about quantitative analysis of RPE atrophic area and subfoveal choroidal thickness after IVR for nAMD. Objective This study was to report the changes of RPE atrophic area and subfoveal choroidal thickness after IVR for nAMD. Methods A prospective series cases-observational study was designed.Forty-one eyes of 41 consecutive patients with nAMD were enrolled in Renmin Hospital of Wuhan University from January 2015 to June 2015, and written informed consent was obtained from each patient prior to entering the cohort.The affected eyes received intravitreal injection of 0.05 ml ranibizumab (10 mg/ml) and then followed up monthly for 12 months.The RPE atrophy area around macula and subfoveal choroidal thickness were measured by a newly developed RPE analysis software spectral-domain optical coherence tomography (OCT) and enhanced depth imaging of SD-OCT (EDI-OCT), respectively, and the RPE atrophy area and choroidal thickness changes were compared before IVR and 3, 6 and 12 months after IVR.The correlation between RPE atrophy area and choroidal thickness before and after IVR was analyzed. Results All the patients finished the treating procedure and follow up.The visual acuity (logMAR) after IVR was considerably improved in comparison with before IVR (F=7.631, P 6 times and ≤6 times (r=0.297, -0.327), but these results were not statistically significant (P=0.248, 0.282, 0.103). At the end of the follow up, weak linear correlations were seen in RPE atrophy area change values and choroidal thickness change values with IVR times (rs=-0.266, 0.342), but these results were not statistically significant (P=0.148, 0.060). Conclusions IVR for nAMD can lead to subfoveal choroid atrophy instead of RPE atrophy.IVR does not accelerate the atrophy progression of both RPE and choroid. Key words: Antibodies, monoclonal, humanized/therapeutic use; Ranibizumab; Wet age-related macular degeneration/drug therapy; Choroidal neovascularization/drug therapy; Intravitreal injection; Pigment epithelium of eye; Choroidal thickness/drug effects; Tomography, optical coherence

Differential Disease Progression in Atrophic Age-Related Macular Degeneration and Late-Onset Stargardt Disease.

To compare the disease course of retinal pigment epithelium (RPE) atrophy secondary to age-related macula degeneratio (AMD) and late-onset Stargardt disease (STGD1). Patients were examined longitudinally by fundus autofluorescence, near-infrared reflectance imaging, and best-corrected visual acuity (BCVA). Areas of RPE atrophy were quantified using semi-automated software, and the status of the fovea was evaluated based on autofluorescence and near-infrared reflectance images. Mixed-effects models were used to compare atrophy progression rates. BCVA loss and loss of foveal integrity were analyzed using Turnbull's estimator. A total of 151 patients (226 eyes) with RPE atrophy secondary to AMD and 38 patients (66 eyes) with RPE atrophy secondary to late-onset STGD1 were examined for a median time of 2.3 years (interquartile range, 2.7). Mean baseline age was 74.2 years (SD, 7.6) in AMD and 63.4 (SD, 9.9) in late-onset STGD1 (P = 1.1 × 10-7). Square root atrophy progression was significantly faster in AMD when compared with late-onset STGD1 (0.28 mm/year [SE, 0.01] vs. 0.23 [SE, 0.03]; P = 0.030). In late-onset STGD1, the median survival of the fovea was significantly longer when compared with eyes with AMD (8.60 vs. 3.35 years; P = 0.005) with a trend to a later BCVA loss of ≥3 lines (5.97 vs. 4.37 years; P = 0.382). These natural history data indicate differential disease progression in AMD versus late-onset STGD1. The results underline the relevance of refined phenotyping in elderly patients presenting with RPE atrophy in regard to prognosis and design of interventional trials.

CHOROIDAL ALTERATIONS IN ABCA4-RELATED RETINOPATHY

To investigate choroidal alterations in ABCA4-related retinopathy. Mean choroidal thickness and subfoveal choroidal thickness were measured in the right eyes of 40 patients with ABCA4-related retinopathy using enhanced-depth imaging optical coherence tomography. The right eyes of 65 age-matched healthy subjects were used for comparison. Compared with controls, patients with ABCA4-related retinopathy revealed a reduced subfoveal choroidal thickness ([mean ± SEM] 347 ± 10 μm vs. 302 ± 12 μm; P = 0.006) and mean choroidal thickness (315 ± 9 μm vs. 275 ± 10 μm; P = 0.005). This difference was mainly due to choroidal thinning in eyes with reduced photopic and/or scotopic amplitudes on full-field electroretinography. Atrophy of the retinal pigment epithelium (RPE) was associated with a thinner choroid compared with eyes without RPE atrophy (subfoveal choroidal thickness: 277 ± 17 μm vs. 341 ± 16 μm; mean choroidal thickness: 252 ± 13 μm vs. 313 ± 13 μm; both, P ≤ 0.001), but choroidal thinning was not restricted to the area of RPE atrophy. Choroidal thickness was similar to controls when RPE atrophy and functional loss were limited to the central retina. There was no association between visual acuity and choroidal thickness. The results indicate choroidal alterations in widespread ABCA4-related retinopathy, especially when associated with atrophy of the RPE. The absence of focal choroidal thinning in areas of RPE atrophy is suggestive for a diffusible factor from the RPE sustaining the choroidal structure.

TREAT-AND-EXTEND REGIMEN WITH AFLIBERCEPT FOR RETINAL ANGIOMATOUS PROLIFERATION.

To evaluate the effects of aflibercept therapy using a treat-and-extend regimen on treatment-naïve retinal angiomatous proliferation (RAP) and development of retinal pigment epithelium (RPE) atrophy. We retrospectively studied 17 treated eyes with RAP and 13 untreated fellow eyes. We assessed best-corrected visual acuity (BCVA) in logarithm of the minimal angle of resolution (logMAR) units and recorded the total number of injections for 12 months. Central macular thickness (CMT) and central choroidal thickness (CCT) were assessed by optical coherence tomography (OCT), and RPE atrophy extent in the macular area was assessed by fundus autofluorescence. Average BCVA in eyes with RAP was 0.57 logMAR units (Snellen 20/74 or approximately 56.5 ETDRS letters) before treatment and significantly improved to 0.38 (Snellen 20/48 or approximately 66 ETDRS letters, P < 0.01) after 3 months and 0.32 (Snellen 20/42 or approximately 69 ETDRS letters, P < 0.01) after 12 months. Average CMT was 340 μm before treatment and significantly reduced to 133 μm (P < 0.001) after 3 months and 130 μm (P < 0.001) after 12 months. Average CCT was 147 μm before treatment, 123 μm (P < 0.01) after 3 months, and 131 μm (P < 0.01) after 12 months. Average total number of injections was 7.2. Average area of RPE atrophy enlarged by 1.00 mm in treated eyes compared with 0.34 mm in fellow eyes (P < 0.01). The enlarged area of RPE atrophy was inversely correlated with central choroidal thickness after 12 months (rs = -0.49, P < 0.01) and positively correlated with the number of injections (rs = 0.58, P < 0.01). Treat-and-extend intravitreal therapy with aflibercept may be effective for improvement and stabilization of visual acuity and exudative change in eyes with RAP. However, choroidal thinning during the treatment regimen may accelerate enlargement of RPE atrophy.

Patterned macular dystrophy as the first sign of maternally‐inherited diabetes and deafness (MIDD)

PurposeMaternally inherited diabetes and deafness (MIDD) is a mitochondrial disorder characterized by the mutation of the mitocondrial DNA (mtDNA) at the 3,243 position. The prevalence accounts for 0.5–2.8% of all cases of diabetes. In more than 80% of cases it is associated with a good prognosis bilateral pattern macular dystrophy. We show the importance of ocular examination to diagnose MIDD.MethodsWe present a case report of MIDD.ResultsA 42 year‐old man was referred for a nonspecific blurred vision in both eyes since two months ago. Diabetes mellitus type 1 and migraine had been diagnosed at the age of 20. The patient wore a hearing aid because he had bilateral sensorineural hearing loss. Best‐corrected visual acuity (BCVA) was 20/20 in both eyes. Fundus examination revealed bilateral hyperpigmented lesions surrounding the macula combined with depigmented areas of retinal pigment epithelium (RPE). Spectral‐domain optical coherence tomography (SD‐OCT) showed hyperreflective dome‐shaped lesions corresponding to a hyperpigmented areas that seemed to originate from the RPE. Fundus autofluorescence (FAF) was characterized by a diffuse speckled appearance of the macula with decreased FAF signal in areas of RPE atrophy and irregular increased FAF signal between the areas of RPE atrophy. Results from automated static perimetry and magnetic resonance imaging (MRI) of the brain was unremarkable. We suspected MIDD and genetic testing of mtDNA confirmed a point mutation at the locus 3,243 with 85% heteroplasmy.ConclusionsOphthalmologists need to be aware in patients presenting patterned dystrophies of the RPE in the context of diabetes or deafness. It is possible that there are other family members with undiagnosed disorders related to mitochondrial mutation who would benefit from ophthalmic evaluation, auditory testing and screening for diabetes mellitus.