Hyperpigmentary Changes Research Articles

Multimodal Imaging, OCT B-Scan Localization, and En Face OCT Detection of Macular Hyperpigmentation in Eyes with Intermediate Age-Related Macular Degeneration.

PurposeMultimodal imaging was used to identify and characterize the cause of hyperpigmentation seen on color fundus images (CFIs) of eyes with intermediate age-related macular degeneration (iAMD).DesignRetrospective review of a prospective study.ParticipantsPatients with iAMD.MethodsColor fundus images with macular hyperpigmentation were compared with same-day images obtained using fundus autofluorescence (FAF), near infrared reflectance (NIR), and swept-source (SS) OCT imaging. Two SS OCT en face slabs were generated: a retinal slab to identify hyperreflective foci within the retina and a slab from beneath the retinal pigment epithelium (RPE; the sub-RPE slab) that was used to detect regions that cause decreased light transmission into the choroid, also known as hypotransmission defects. All images were registered to allow for qualitative comparisons by 2 independent graders.Main Outcome MeasuresComparison between foci of macular hyperpigmentation seen on CFIs with the detection of these regions on FAF, NIR, and SS OCT en face images.ResultsCompared with CFIs, FAF imaging seemed to be the least sensitive method for the detection of hyperpigmentation, whereas NIR and SS OCT imaging reliably detected these hyperpigmented areas. Although NIR imaging detected most of the hyperpigmentation seen in CFIs, SS OCT imaging detected all the areas of hyperpigmentation and anatomically localized these areas by using both en face and B-scan images. En face OCT slabs of the retina and sub-RPE region were registered to the CFIs, and areas of hyperpigmentation were shown to correspond to hyperreflective foci in the retina and regions of thickened RPE seen on OCT B-scans. Although both hyperpigmentation and early atrophic lesions appeared bright on NIR imaging, en face SS OCT imaging was able to distinguish these lesions because hyperpigmentary changes appeared dark and early atrophic lesions appeared bright on the sub-RPE slab.ConclusionsEn face OCT imaging in conjunction with OCT B-scans were able to identify and localize the hyperpigmentation seen in CFIs reliably. This hyperpigmentation was not only associated with intraretinal hyperreflective foci, but also corresponded to areas with a thickened RPE.

ULTRAWIDEFIELD PSEUDOCOLOR RETINAL IMAGING VERSUS REAL-COLOR FUNDUS PHOTOGRAPHY FOR DETECTION OF INTRARETINAL PIGMENT MIGRATION IN AGE-RELATED MACULAR DEGENERATION.

To compare pseudocolor Optos ultrawidefield (UWF) retinal images with conventional real-color fundus photography (CFP) for detecting macular hyperpigmentary changes in intermediate age-related macular degeneration. This retrospective study included 50 patients diagnosed with intermediate age-related macular degeneration. All patients underwent Optos imaging and CFP. The overall accuracy to visualize hyperpigmentation and its morphologic features was graded by two independent readers using a standardized grid. Structural and en face optical coherence tomography images were correlated with UWF and CFP images to determine spatial correspondence of pigment clumping on fundus images and hyperreflective foci on optical coherence tomography. One hundred eyes of 50 patients had hyperpigmentary changes on funduscopic examination and were included. The intragraders and intergraders agreements were high for all measurements (P < 0.001). At least one hyperpigmentary changes within the standardized grid was detected in 93% using CFP and 100% using UWF camera (P = 0.02). The total area of hyperpigmentation measured on UWF images was significantly higher than on CFP images (P < 0.001). There was a significant correlation between the presence of hyperpigmentary changes on both CFP and UWF images and hyperreflective foci on structural optical coherence tomography (P < 0.001). Ultrawidefield fundus images allow high detection and accurate quantification of macular hyperpigmentary changes in intermediate age-related macular degeneration compared with conventional CFP.

Macular hyperpigmentary changes in ABCA4-Stargardt disease

BackgroundStargardt disease (STGD) and age-related macular degeneration (AMD) share clinical and pathophysiological features. In AMD, macular hyperpigmentary changes are associated to a worse prognosis. The purpose of this study was to characterize macular hyperpigmentary changes in patients with STGD and associate them with the severity of phenotype.Materials and methodsThis retrospective cross-sectional study included 141 patients with STGD. Hyperpigmentary changes were evaluated on color fundus photography and spectral-domain optical coherence tomography. Severity of phenotype was assessed by full-field electroretinogram (ffERG) and fundus autofluorescence (FAF) patterns, and visual acuity (VA).ResultsThirty patients (21.7%) showed macular hyperpigmentary changes in four distinct patterns. Out of seventeen patients who had follow-up images, eleven patients demonstrated increases of the hyperpigmented lesions, and progression of the underlying RPE atrophy overtime. VA remained stable. Of 28 patients who had ffERG, 17 patients presented with reduction of photopic and scotopic responses, while 8 presented with reduction of photopic responses only, and 3 presented with preserved photopic and scotopic responses. Of 25 patients who had FAF available, 12 presented with widespread disease extending anteriorly to the vascular arcades, while eight presented with widespread disease, extending beyond the vascular arcades, and 5 presented with disease confined to the foveal area.ConclusionIn this study, we demonstrated that patients with STGD with macular hyperpigmented lesions had a severe phenotype. Overtime, hyperpigmented lesions increased in size, spread across the retina, and migrated to different retinal layers. Macular hyperpigmentation may be a marker of advanced stage of the disease.

Quantitative Analysis of the Ellipsoid Zone Intensity in Phenotypic Variations of Intermediate Age-Related Macular Degeneration.

Reduction of the ellipsoid zone (EZ) intensity has been reported in eyes with age-related macular degeneration (AMD). This study determined whether overall EZ intensity, in retinal locations undisturbed by pathologic features, is associated with the presence of clinical features, which are known important phenotypic risk factors for disease progression, large drusen, reticular pseudodrusen (RPD), and pigmentary abnormalities. A horizontal B-scan through the foveola on spectral-domain optical coherence tomography (SD-OCT) was performed in both eyes of 75 participants with bilateral intermediate AMD and 10 age-similar control participants. Eyes with AMD were classified as per the presence of large drusen, RPD, and hyperpigmentary changes. The relative EZ intensity profile, up to an eccentricity of 3400 μm, was averaged over seven 1000-μm retinal segments. The association between relative EZ intensity profile over seven retinal segments and AMD pathologic features was analyzed. The average relative EZ intensities were significantly reduced in eyes with intermediate AMD compared to normal eyes (P ≤ 0.025) and with increasing age (P ≤ 0.020). On multivariate analyses, only the presence of hyperpigmentary changes and increasing age were significantly associated with reduced overall relative intensities (P ≤ 0.024), but not the presence of large drusen or RPD (P ≥ 0.115). The presence of hyperpigmentary change in the macula in association with large drusen, not large drusen alone, nor large drusen with RPD, was significantly associated with a generalised reduction in EZ intensity. Quantitative assessment of the relative EZ intensity may serve as an effective biomarker of disease severity and progression.

Automated Retinal Image Analysis for Evaluation of Focal Hyperpigmentary Changes in Intermediate Age-Related Macular Degeneration.

PurposeTo develop and evaluate a software tool for automated detection of focal hyperpigmentary changes (FHC) in eyes with intermediate age-related macular degeneration (AMD).MethodsColor fundus (CFP) and autofluorescence (AF) photographs of 33 eyes with FHC of 28 AMD patients (mean age 71 years) from the prospective longitudinal natural history MODIAMD-study were included. Fully automated to semiautomated registration of baseline to corresponding follow-up images was evaluated. Following the manual circumscription of individual FHC (four different readings by two readers), a machine-learning algorithm was evaluated for automatic FHC detection.ResultsThe overall pixel distance error for the semiautomated (CFP follow-up to CFP baseline: median 5.7; CFP to AF images from the same visit: median 6.5) was larger as compared for the automated image registration (4.5 and 5.7; P < 0.001 and P < 0.001). The total number of manually circumscribed objects and the corresponding total size varied between 637 to 1163 and 520,848 pixels to 924,860 pixels, respectively. Performance of the learning algorithms showed a sensitivity of 96% at a specificity level of 98% using information from both CFP and AF images and defining small areas of FHC (“speckle appearance”) as “neutral.”ConclusionsFHC as a high-risk feature for progression of AMD to late stages can be automatically assessed at different time points with similar sensitivity and specificity as compared to manual outlining. Upon further development of the research prototype, this approach may be useful both in natural history and interventional large-scale studies for a more refined classification and risk assessment of eyes with intermediate AMD.Translational RelevanceAutomated FHC detection opens the door for a more refined and detailed classification and risk assessment of eyes with intermediate AMD in both natural history and future interventional studies.

Imatinib mesylate-induced hyperpigmentation of the nose and palate.

Dear Editor: Imatinib mesylate, a tyrosine kinase inhibitor targeting c-kit and platelet-derived growth factor, has been used for the treatment of hematologic malignancies. Its cutaneous adverse effects are diverse, including maculopapular exanthema, vasculitis, and Stevens-Johnson syndrome1. A well-established pigmentary change is hypopigmentation, which is characterized by generalized skin lightening, vitiligo-like lesions, and hair graying2. However, paradoxical hyperpigmentary changes were rarely observed3,4. We present a case of hyperpigmentation of the nose and hard palate associated with imatinib mesylate. A 58-year-old man was referred for discoloration of the nose. He was diagnosed with chronic myelogenous leukemia and was treated with imatinib mesylate (Gleevec; Novartis, Basel, Switzerland). Not long after imatinib treatment, he noticed insidious pigmentary changes on his nose. He had no history of skin eruptions or use of other medication. Physical examination revealed an ill-defined, slate-gray patch on the nose and on the hard palate, which suggested a diagnosis of dermal pigmentary disorders including acquired bilateral nevus of Ota-like macules (Fig. 1). Biopsy of the lesional skin and perilesional normal skin of the nose was performed. Fontana-Masson staining showed increased basal pigmentation and dermal melanophages in the lesional skin compared with the perilesional normal skin (Fig. 2A). Imunohistochemical staining with the NKI/beteb antibody confirmed the absence of melanocytes in the dermis (Fig. 2B). Therefore, the pigmentation was speculated to be imatinib-associated hyperpigmentation. Although hypopigmentation is a well-known pigmentary change due to imatinib treatment, paradoxical hyperpigmentation has been rarely reported. In hyperpigmentation, the changes are not generalized like hypopigmentary changes. The disorder pigmentation is localized in the oral cavity, including the hard palate and gum, nose, ear lobe, or nails3,4. The present case was consistent with these features, and the patient showed localized pigmentation on the nose and hard palate. There has been no report about the prognosis of this pigmentary change. In case of hypopigmentation, it could be reversible when the doses are tapered or the treatment is stopped2. Our patient is continuing imatinib treatment, and there has been no change in the pigmentation. It has been suggested that imatinib-induced hypopigmentation is mediated by c-kit inhibition, resulting in reduced tyrosinase activity in melanocytes5. The mechanism of this paradoxical hyperpigmentation is unclear. However, an in vitro study has shown the stimulating effect of imatinib on the tyrosinase activity of cultured melanocytes, which suggests the target-dependent stimulating effects of imatinib mesylate on pigmentation. Further studies are required to elucidate these pigmentary changes related to imatinib mesylate medication. Herein, we report a case of paradoxical hyperpigmentation of the nose and hard palate after imatinib mesylate treatment, warranting further evaluation of this mechanism. Fig. 1 Ill-defined slate grey-colored pigmentation on nose (A) and palate (B). Fig. 2 (A) Increased epidermal pigmentation and dermal melanophages in the lesional skin (L) compared with perilesional normal skin (N) (Fontana-Masson stainining, ×200). (B) There were no melanocytes in the dermis (gp100, ×200).

Markers of disease progression in atrophic AMD

AbstractGeographic Atrophy (GA) is a common cause for severe visual loss in age‐related macular degeneration (AMD). In contrast to neovascular AMD in which efficient therapy is now available with intravitreally administered inhibitors of VEGF, there is as yet no therapy available for patients with GA. Natural history studies have demonstrated a continuous progression of outer retinal atrophy in patients with GA. Hereby, a high interindividual variability has been documented with regard to enlargement rates of GA ptaches over time. Various markers of disease progression have been identified including phenotypic charatersitcs on fundus photographs such as soft drusen and hyperpigmentary changes. Furthermore, certain abnormal patterns of increased fundus autofluorescence (FAF) on confocal SLO images have been shown to represent risk characteristics for GA evolution and aloow disrimintaion of slow vs. fast progressors. The status of the fellow also has an imapct on progression rates. SD‐OCT imaging is currently evaluated in ongoing longitudinal studies with respect to specific microstructural alterations in the junctional zone of GA and their impactz for future progression. Idenfication of progrnostic markers is not o9nly important for a better understandibng of the disease process, but also for the design and conduct of interventional clinical trials in patients with GA as enrichment for fast progressors allows to perform such trials in an acceptable time period in a relatively slowly progressing disease, to reduce costs for clinical developments and to increase the likelyhood for the identification of a therapeutic signal.

Spatial Correlation between Hyperpigmentary Changes on Color Fundus Photography and Hyperreflective Foci on SDOCT in Intermediate AMD

Macular hyperpigmentation is associated with progression from intermediate to advanced age-related macular degeneration (AMD). The purpose of this study was to accurately correlate hyperpigmentary changes with spectral domain optical coherence tomography (SDOCT) hyperreflective foci in eyes with non-advanced AMD. A prospective cross-sectional analysis of 314 eyes (314 subjects) with intermediate AMD was performed in the multicenter Age-Related Eye Disease Study 2 (AREDS2) Ancillary SDOCT Study to correlate hyperpigmentary changes on color fundus photographs (CFP) with abnormal morphology on SDOCT. Spatial coregistration was performed with an automated algorithm in two nonoverlapping subsets of 20 study eyes, which permitted double-masked CFP and SDOCT grading by certified investigators. Macular CFP hyperpigmentation was significantly associated with SDOCT intraretinal hyperreflective foci in the 314 study eyes (P < 0.001). In a substudy of 40 eyes, automated intermodality spatial coregistration was successfully achieved in all 136 (100%) retinal regions selected for CFP and SDOCT grading. In one subset of 20 study eyes, 28 of 39 (71.8%) retinal CFP regions with hyperpigmentation were correlated with focal hyperreflectivity on SDOCT, versus seven of 39 (17.9%) control regions (P < 0.001). In another subset of 20 eyes, 21 of 29 (72.4%) SDOCT regions with hyperreflective foci were correlated with hyperpigmentary changes on CFP, versus two of 29 (6.9%) control regions (P < 0.001). A novel algorithm achieves automated intermodality spatial coregistration for masked grading of regions selected on CFP and SDOCT. In intermediate AMD, macular hyperpigmentation has high spatial correlation to SDOCT hyperreflective foci and often represents the same anatomical lesion. (ClinicalTrials.gov number, NCT00734487.).

Infrared imaging and spectral-domain optical coherence tomography findings correlate with microperimetry in acute macular neuroretinopathy: a case report

IntroductionSpectral-domain optical coherence tomography findings in a patient with acute macular neuroretinopathy, and correlation with functional defects on microperimetry, are presented.Case presentationA 25-year old Caucasian woman presented with bitemporal field defects following an upper respiratory tract infection. Her visual acuity was 20/20 in both eyes and a dilated fundus examination revealed bilateral hyperpigmentary changes in the papillomacular bundle. Our patient underwent further evaluation with spectral-domain optical coherence tomography, infrared and fundus autofluorescence imaging. Functional changes were assessed by microperimetry. Infrared imaging showed the classic wedge-shaped defects and spectral-domain optical coherence tomography exhibited changes at the inner segment-outer segment junction, with a thickened outer plexiform layer overlying these areas. Fluorescein and indocyanine green angiography did not demonstrate any perfusion defects or any other abnormality. Microperimetry demonstrated focal elevation in threshold correlating with the wedge-shaped defects in both eyes.ConclusionSpectral-domain optical coherence tomography findings provide new evidence of the involvement of the outer plexiform layer of the retina in acute macular neuroretinopathy.

Phthriasis Palpebrarum Mimicking Lid Eczema and Blepharitis

Phthiriasis palpebrarum (PP) is a rare eyelid infestation caused by phthirus pubis. We report a case of PP mimicking lid eczema and blepharitis. A 68-year-old woman had moderate itching in both eyes. Her initial diagnosis was considered to be lid eczema or blepharitis because of findings similar to exfoliative lesions and color changes in eyelids and to excretions over eyelashes. Careful observation revealed many lice and translucent nits, protuberances and hyperpigmentary changes, and the buried lice in both eyelids. No hyperemia or secretion was observed on the lids and in the conjunctiva in both eyes. The patient was treated with pilocarpine hydrochloride 4% drops. At the end of the first week, no louse or nit was present. Although it was known that PP is a rare cause of blepharoconjunctivitis, it might observe as an isolated infestation of the eyelids and this condition can easily be misdiagnosed as lid eczema and blepharitis.

Reduced Foveolar Choroidal Blood Flow in Eyes with Increasing AMD Severity

In an earlier study, the authors reported that foveolar choroidal blood flow (ChBFlow) decreases in patients with AMD and drusen. To explore further the choroidal circulatory changes in patients with AMD, the relationship between ChBFlow and fundus features associated with increased risk of choroidal neovascularization (CNV) were investigated. The study included 26 control eyes of 17 normal subjects and 163 eyes with early AMD characteristics of 123 patients with AMD. The AMD study eyes were divided into three groups according to increasing risk for development of CNV: (1) drusen > or =63 microm, no RPE hyperpigmentary changes in the study eye, and no CNV in the fellow eye; (2) drusen > or =63 microm, RPE hyperpigmentary changes in the study eye, and no CNV in the fellow eye; and (3) eyes with CNV in the fellow eye. Laser Doppler flowmetry was used to assess relative foveolar choroidal blood velocity (ChBVel), volume (ChBVol), and flow (ChBFlow). Differences in the mean circulatory parameters were assessed by analysis of variance (ANOVA) and test of linear trend. Mean ChBVel, ChBVol, and ChBFlow decreased with increased risk for CNV (linear trend, P < 0.05). The lowest circulatory parameters were observed in the eyes with the highest risk for CNV development. Trends for ChBVel and ChBFlow were still significant after adjustment for multiple factors. There is a systematic decrease in choroidal circulatory parameters with an increase in the severity of AMD features associated with risk for the development of CNV, suggesting a role for ischemia in the development of CNV.