Pachychoroid Pigment Epitheliopathy Research Articles

Clinical Characteristics of Punctate Hyperfluorescence Spots in the Fellow Eye of Patients with Unilateral Macular Neovascularization with No Drusen

Objectives: To assess the clinical characteristics of patients with macular neovascularization (MNV) with no drusen in the fellow eye, we investigated the incidence of MNV in fellow eyes and the outcomes of intravitreal aflibercept (IVA) monotherapy in MNV eyes of patients with unilateral MNV with a punctate hyperfluorescence spot (PHS) in the fellow eye. Methods: We retrospectively studied 58 treatment-naïve patients with unilateral MNV with no drusen in the fellow eye. Patients were classified into a PHS group (n = 29) or no-PHS group (n = 29) based on the presence of PHS. We evaluated the incidence of MNV in the fellow eye, and the retreatment rate after initiation of three monthly aflibercept injections over one year. Results: Fellow eyes in the PHS group had a thicker choroid (p < 0.05) and higher prevalence of pachychoroid pigment epitheliopathy (PPE) (p < 0.001). MNV eyes in the PHS group had a thicker choroid (p = 0.09). The PHS group had a lower retreatment rate (p < 0.05) and required fewer injections (p < 0.05) than the no-PHS group. MNV developed in one eye in both the PHS and no-PHS groups, and both cases occurred in areas of hypofluorescence on indocyanine green angiography within the PPE area before the onset of MNV. Conclusions: The PHS group frequently exhibited pachychoroid disease characteristics and responded better to IVA monotherapy than the no-PHS group. These groups may represent distinct populations of patients with unilateral MNV with no drusen in the fellow eye.

Pachychoroid pigment epitheliopathy in keratoconic eyes.

To report the association between keratoconus (KC) and pachychoroid pigment epitheliopathy (PPE). As secondary outcome, we explored the relation between subfoveal choroidal thickness (SFCT) and topometric indexes. Retrospective, observational, cross-sectional, case-control study. Multicentric study including patients with KC and healthy controls. Each subject underwent a complete ophthalmological visit, Placido-based corneal topography, Scheimpflug corneal tomography and spectral-domain OCT (SD-OCT) with the enhanced depth imaging (EDI) mode on. Linear mixed models (LMM) were employed for comparison between groups, and to examine the impact of different topometric factors on SFCT. KC stages were defined according to Belin grading. Overall, 56 eyes from 35 KC patients and 52 eyes from 27 healthy, age- and axial length-matched control subjects were included in the study. PPE was found in 10 (17.9%) eyes from 8 KC patients, whereas was absent in all healthy controls. SFCT was statistically significantly higher in keratoconic eyes (median: 390µm; interquartile range (IQR): 339 - 425µm) compared to healthy eyes (median: 240µm; IQR: 200 - 288µm) (p < 0.001). SFCT did not differ across different KC stages and between keratoconic eyes with and without PPE. PPE is a relatively frequent finding in eyes with KC, being present in about 1 out of 6 cases, regardless of disease stage. What is known: Keratoconus (KC) is a corneal disorder commonly associated with other chorioretinal abnormalities. It is well known that keratoconic eyes display increased choroidal thickness, and the rare association between KC and central serous chorioretinopathy (CSC) has already been reported in the literature. We identified an association between KC and pachychoroid pigment epitheliopathy (PPE), a precursor or forme fruste of pachychoroid diseases, such as CSC. PPE presence is independent from corneal parameters and is observed in about 1 out 6 KC eyes.

PREDNISOLONE EYE DROPS AS A POTENTIAL TREATMENT IN NONNEOVASCULAR PACHYCHOROID-RELATED DISEASES.

To investigate the functional and structural outcomes after treatment with prednisolone eye drops in the following pachychoroid-related diseases: chronic central serous chorioretinopathy, pachychoroid pigment epitheliopathy, and peripapillary pachychoroid syndrome. In this retrospective study, 54 eyes of 48 patients with pachychoroid-related disease were treated with prednisolone acetate 1% eye drops 3 times a day. Change in macular volume and retinal central subfield thickness on optical coherence tomography was measured. In addition, the foveal or complete resolution of fluid and the change in visual acuity were studied. The follow-up visit was at a mean of 41.2 ± 14.5 days. In the 44 eyes with chronic central serous chorioretinopathy, a significant reduction in retinal central subfield thickness ( P < 0.001) and macular volume ( P < 0.001) was observed. Foveal intra- or subretinal fluid resolved completely in 22% of the eyes. In the 8 peripapillary pachychoroid syndrome eyes, a reduction in the nasal retinal thickness was observed ( P = 0.025). One of the 2 pachychoroid pigment epitheliopathy eyes showed structural improvement. No significant change in visual acuity was observed in any of the pachychoroid spectrum diseases. In patients with chronic central serous chorioretinopathy, peripapillary pachychoroid syndrome, and pachychoroid pigment epitheliopathy, anatomical improvement was observed after therapy with prednisolone eye drops. Visual acuity did not change significantly.

Understanding the relationship between pachychoroid spectrum disorders and retinitis pigmentosa: A review of the evidence.

This study aims to investigate the relationship between pachychoroid spectrum disorders and retinitis pigmentosa (RP) or rod-cone dystrophy through a comprehensive literature review. The purpose is to explore the association between these disorders, understand their underlying mechanisms, and summarize the existing hypotheses and opinions. A thorough review of the literature was conducted using PubMed, focusing on articles related to central serous chorioretinopathy (CSC), RP, pachychoroid pigment epitheliopathy, pachychoroid neovasculopathy, polypoidal choroidal vasculopathy, focal choroidal excavation, peripapillary pachychoroid neovasculopathy, and peripheral exudative hemorrhagic chorioretinopathy. Relevant studies were selected for a detailed narrative review and analysis. Several studies have reported the coexistence of CSC and RP, indicating a potential association between the two conditions. The dysfunction of the retinal pigment epithelium is proposed as a common factor. Choroidal thinning is observed in RP, but conflicting results exist regarding choroidal thickness (CT). While some studies support choroidal thinning in RP, others suggest preserved or increased thickness. Additionally, cases of pachychoroid neovasculopathy and polypoidal choroidal vasculopathy in RP have been reported, suggesting an overlap between these conditions. The literature suggests conflicting reports on CT changes in RP. Future research should focus on large-scale studies using comprehensive imaging techniques, genetic analysis, and long-term follow-up to uncover the underlying mechanisms and determine the prevalence of pachychoroid spectrum disorders in RP patients.

Choroidal Thickness in Mild Autonomous Cortisol Secretion.

To evaluate the patients with mild autonomous cortisol secretion (MACS) by means of choroidal thickness (CT) and also investigate whether CT may be a diagnostic tool in the management of MACS or not. Twenty-seven patients with MACS and 25 age-sex-matched healthy controls were enrolled in this cross-sectional comparative study. All the participants underwent CT measurement by using Spectralis optical coherence tomography (Heidelberg Engineering, Heidelberg, Germany) with enhanced deep imaging mode at the subfoveal, 500-1000-1500 µm nasal and 500-1000-1500 µm temporal to the foveola. The groups were similar in terms of spherical equivalence, age and axial lengths. The mean CT was significantly thicker in patients with MACS than controls in all measurement quadrants (p<0.001). There was no significant correlation between CT, size of the adenoma, basal cortisol, 1mg dexamethasone suppression test, salivary cortisol, 24-hour total urine-free cortisol, ACTH and DHEAS levels. However, 2 mg dexamethasone suppression test results were found to be significantly correlated with CT in temporal 500-1000 and 1500 µm quadrants (r=0.436, p=0.023, r=0.443, p=0.021 and r=0.488, p=0.010, respectively). Five (18.5%) eyes had pachychoroid pigment epitheliopathy in the MACS group. CT increases in patients with MACS and those tend to have pachychoroid pigment epitheliopathy more frequent than healthy individuals. A thicker choroid in the patients with MACS may be a novel biomarker both as a diagnostic tool for the degree of hypercortisolemia and cortisol-related comorbidity.

Long-term visual outcomes in pachychoroid spectrum diseases and its associating factors of eyes with chronic central serous chorioretinopathy

To analyze the long-term visual outcomes of pachychoroid spectrum diseases (PSD). Retrospective study. We reviewed the medical charts of consecutive patients with PSD, including focal choroidal excavation (FCE), pachychoroid pigment epitheliopathy (PPE), central serous chorioretinopathy (CSC), and pachychoroid neovasculopathy (PNV). The patients initially visited the Tokyo University Hospital from January 2008 to March 2021. Survival analyses were performed, in which loss of vision was defined as visual acuity (VA) of 0.2 logarithm of minimal angle of resolution (logMAR) or worse, 0.5 logMAR or worse, or VA worsening by 0.3 logMAR or greater. Moreover, we further investigated factors associated with visual prognosis, particularly in the CSC group. A total of 741 eyes of 638 patients were included in this analysis. The CSC or PNV group showed significantly worse visual prognosis than the FCE&PPE group for VA to 0.2 logMAR or worse (P = 0.0117 or 0.0001, respectively) and for VA worsening by 0.3 logMAR or greater (P = 0.0283 or 0.0037, respectively). In the CSC group, unlike age, sex, or treatment history, the accumulative duration of subfoveal fluid existence ≥ 12 months (continuous or intermittent) was significantly associated with visual prognosis (P < 0.0001). Among PSD, CSC and PNV were associated with a higher risk of vision loss in the long term than FCE and PPE. The duration of subretinal fluid existence was identified as a significant factor affecting long-term visual outcomes in CSC.

Choroidal Vein Alterations in Pachychoroid Disease With Choroidal Vascular Hyperpermeability: Evaluated by Wide-Field Indocyanine Green Angiography.

The purpose of this study was to investigate choroidal vein (ChV) morphological features in pachychoroid disease (PCD) with choroidal vascular hyperpermeability (CVH). This retrospective study assessed subfoveal choroidal thickness (SFCT) and CVH area numbers and locations of recruited patients with PCD using multimodal images. ChV alteration patterns, including fusiform, bulbosity, sausaging, confluence, and anastomoses, as well as asymmetric ChVs, dominant ChVs, and non-dominant ChVs, were evaluated using wide-field indocyanine green angiograms. Of 68 PCD eyes from 35 patients (mean age: 46.16 ± 6.28 years, 71.4% men), 2.9% had uncomplicated pachychoroid, 32.4% had pachychoroid pigment epitheliopathy (PPE), 55.9% central serous chorioretinopathy (CSC), and 8.8% pachychoroid neovasculopathy (PNV). Mean SFCT was 468.65 ± 131.40 µm. Among 419 CVH areas, ChV fusiform, ChV bulbosity, and ChV sausaging accounted for 35.8%, 35.1%, and 29.1%, respectively; 21.2% had ChV confluence and 11.9% had ChV anastomoses. At CVH areas, 13.1% had retinal pigment epithelium (RPE) leakage. ChV fusiform is steadily declining (37.4%, 36.8%, and 22.9%, respectively), and ChV sausaging, ChV anastomoses, and ChV confluence are increased gradually in the PPE, CSC, and PNV groups (21.4%, 30.0%, and 37.1%; 11.4%, 11.1%, and 20.0%; and 19.8%, 20.9%, and 28.6%, respectively). Dominant ChVs had higher CVH area numbers than non-dominant ChVs in the PPE and CSC groups (P = 0.010, P = 0.001). Different patterns of ChV alterations, including the newly identified ChV confluence, are commonly present at CVH areas in PCD. The CVH areas in PCD eyes are primarily located within the dominant ChVs. These findings provide crucial evidence for advancing our understanding of the underlying mechanisms of PCD pathogenesis.

CURRENT VIEW OF THE SPECTRUM OF PACHYCHOROID DISEASES. A REVIEW.

The term "pachychoroid" (greek pachy- [παχύ] - thick) was first used by Warrow et al. in 2013. It is defined as an abnormal and permanent increase in choroidal thickness ≥ 300 μm, which is caused by dilatation of the choroidal vessels of the Haller's layer, thinning of the Sattler's layer and the choriocapillaris layer. Literary research focused on the current view of pachychoroid spectrum diseases, including clarification of the pathophysiological theories of the formation of "pachychoroid". It is assumed that "pachychoroid" disease has an autosomal dominant type of heredity. Depending on the further activity of various exogenous and/or endogenous factors, pachychoroid diseases may appear. According to the current knowledge, the spectrum of pachychoroid disease covers six clinical entities: pachychoroid pigment epitheliopathy, central serous chorioretinopathy, pachychoroid neovasculopathy, polypoid choroidal vasculopathy, focal choroidal excavation and peripapillary pachychoroid syndrome. In this study, we describe the clinical symptoms and objective findings of focal choroidal excavation and peripapillary pachychoroid syndrome. The current pathophysiological theory of pachychoroid diseases is based on impaired venous outflow from the choroid ("venous overload choroidopathy") and thickening of the sclera in the eyes of affected patients. Pachychoroid diseases should be included in the differential diagnosis of characteristic features observed during multimodal imaging analysis of choroidal changes.

Hyperreflective material in patients with non-neovascular pachychoroid disease

BackgroundThis study aimed to report eleven cases of non-neovascular pachychoroid disease with hyperreflective material (HRM) that occurred in Japanese patients.MethodsA retrospective review of data from eleven patients who had non-neovascular retinal pigment epithelium (RPE) protrusion with HRM in the neurosensory retina between March 2017 and June 2022 was conducted. Clinical examination, color fundus photography, fluorescein angiography, spectral-domain optical coherence tomography (SD-OCT), and OCT angiography data were analyzed. Main outcome measures were patient characteristics, changes in SD-OCT findings, and symptom outcomes.ResultsAll cases had RPE protrusion and HRM with dilated choroidal veins, which were characteristic of pachychoroid disease. However, none of the cases had macular neovascularization (MNV). In 9 eyes (81.8%), HRM improved spontaneously without intervention and resulted in alterations in RPE, referred to as pachychoroid pigment epitheliopathy (PPE) or focal choroidal excavation (FCE). In these cases, symptoms such as metamorphopsia and distortion improved without treatment. In the remaining two cases (18.2%), HRM still persisted during the follow-up period.ConclusionThere are some cases of non-neovascular pachychoroid disorder with HRM, which might be a new entity of pachychoroid spectrum disease or an early stage of PPE or FCE. These cases should not be misdiagnosed as MNV, and careful observation is necessary.

Pachychoroid Spectrum Disorders: An Updated Review.

Pachychoroid disease spectrum is a recent term that has been associated with an increasing number of phenotypes. This review discusses updated findings for each of the typical pachychoroid entities (central serous chorioretinopathy, pachychoroid pigment epitheliopathy, pachychoroid neovasculopathy, polypoidal choroidal vasculopathy, peripapillary pachychoroid syndrome, and focal choroidal excavation), as well as two relatively new additions (peripapillary pachychoroid neovasculopathy and peripheral exudative hemorrhagic chorioretinopathy). Here, we discuss the potential pathogenic mechanisms for these diseases and relevant imaging updates. Finally, we argue for a consistent classification scheme for these entities.

Analysis of the pachychoroid phenotype in an Asian population: methodology and baseline study population characteristics

AimTo describe the clinical characteristics in a cohort of patients with the pachychoroid phenotype and to evaluate the association of ocular and systemic factors with type of complications observed.MethodsWe report...

Natural Course of Pachychoroid Pigment Epitheliopathy.

To investigate the natural course of pachychoroid pigment epitheliopathy (PPE). A retrospective cohort study. From the Kyoto central serous chorioretinopathy (CSC) cohort consisting of 548 patients with CSC as of September 2020, we included consecutive unilateral patients with acute or chronic CSC between January 2013 and December2016. All patients underwent complete ophthalmic examination, including multimodal imaging such as fundus autofluorescence, spectral-domain optical coherence tomography, and fluorescein angiography/indocyanine green angiography and/or optimal coherence tomography angiography. The fellow eyes of eyes diagnosed with CSC were screened for PPE, and their natural course was evaluated. We also evaluated the association of ARMS2 rs10490924, CFH rs800292, TNFRSF10A rs13278062, and GATA5 rs6061548 genotypes with the natural course. Incidence of CSC, pachychoroid neovasculopathy, and pachychoroid geographic atrophy (GA). In total, 165 patients with unilateral CSC (mean age, 55.7±12.6 years; female, 22.4%) were included from the Kyoto CSC cohort. Among them, 148 (89.7%) were diagnosed as having PPE in their non-CSC eye. Survival analysis revealed that 16.8% of PPE eyes developed CSC during the 6-year follow up, whereas non-PPE eyes did not. Although genetic factors did not have significant association with CSC development (P>0.05, log-rank test), choroidal vascular hyperpermeability (CVH) and subfoveal choroidal thickness (SFCT) were significantly associated with CSC incidence (P=0.001, log-rank test). Survival analysis showed that eyes without CVH and eyes with SFCT < 300 μm did not develop CSC during the 6-year follow-up. Pachychoroid neovasculopathy developed in only 1 eye with PPE during a follow-up of 46.4 months. Pachychoroid GA did not develop in any of the studied eyes. This study revealed a natural history of PPE in a relatively large Japanese cohort. Choroidal vascular hyperpermeability and SFCT were significant risk factors for the development of CSC in PPE eyes. Although the current results cannot be generalized for all eyes with PPE, these findings present an important clinical implication.

Choroidal vascularity index: An emerging useful metric for choroidal structure assessment in pachychoroid spectrum disease

AbstractPurpose: To compare choroidal vascularity index (CVI) between eyes with different entities of pachychoroid spectrum diseases (PSD) and a control group.Methods: Eighty‐two eyes of 45 patients with PSD were included in our study. Fifteen eyes had uncomplicated pachychoroid (UCP), 27 eyes had pachychoroid pigment epitheliopathy (PPE), 32 eyes had central serous chorioretinopathy (CSC) and 8 had pachychoroid neovasculopathy (PNV). These eyes were compared to 67 eyes of 34 age‐matched healthy controls. All eyes underwent DRI‐OCT Triton Swept‐Source Optical Coherence Tomography (OCT). B‐scan images were binarized into blood vessels lumen and stroma using ImageJ software. The choroidal vascularity index (CVI) was defined as the ratio of luminal area (LA) to total choroidal area in a subfoveal region of 1500 μm width.Results: Mean CVI in patients with PSD was 64.45 ± 2.74%. A statistically significant difference was found between the PSD patients group and the control group (p &lt; 0.001) with a higher CVI in PSD eyes. Pairwise comparisons revealed statistically significant differences between PPE/PNV groups (p &lt; 0.05), PPE/control groups (p &lt; 0.001), CRSC/control groups (p &lt; 0.05) and CRSC/PPE groups (p = 0.05). The comparison between UCP/control groups, UCP/PPE groups, UCP/CRSC groups, UCP/PNV groups, PNV/control groups and PNV/CRSC groups showed no significant difference.Conclusions: Increased CVI may reflect choroidal vascular structure changes in eyes with PSD. These findings suggest that the CVI could be useful for evaluating choroidal vascular changes in eyes with PSD and predicting a potential progression form PPE to CRSC or PNV.

Pigment epithelium and choroid changes in pachychoroid pigment epitheliopathy: A descriptive study

AbstractPurpose: To describe characteristic elementary lesions of retinal pigment epithelium and choroidal vascular parameters determined by swept source optical coherence tomography (SS‐OCT) and OCT‐angiography (OCT‐A) in eyes with pachychoroid pigment epitheliopathy.Methods: Twenty‐seven patients with retinal pigment epithelium (RPE) abnormalities associated to pachychoroid features, with no history or findings indicative of subretinal fluid or soft drusen were evaluated. All eyes underwent comprehensive ophthalmic examination, fundus photography, SS‐OCT and OCT‐A. After binarization of B‐scan images with ImageJ Software, the choroidal vascularity index (CVI), the choroidal vascularity proportion (CVP) and flow voids area were calculated.Results: A total of 27 eyes of 23 patients, 19 of whom were male (70.37%), with a mean age of 59.11 ± 12.76 years were enrolled in this study. We detected six different types of RPE lesions: focal disruption in ellipsoid and interdigitation zones in 18 eyes (66.66%), RPE elevation with microbreak appearance in 12 eyes (44.44%), RPE thickening in 10 eyes (37.03%), small pigment epithelium detachment in seven eyes (25.92%), RPE spike in five eyes (18.51%) and outer nuclear layer thinning in five eyes (18.51%). The subfoveal choroidal thickness (SFCT) was 399, 78 ± 88, 13 μm. The mean inner choroidal thickness was 87.18 ± 36.67 μm. The CVI was 65.28 ± 3.35%. The CVP was 59.10 ± 0.58% in the choriocapillaris and 59.69 ± 1.42% in the Haller layer. The total choriocapillaris flow void area was 39.87 ± 1.21%.Conclusions: SS‐OCT and OCT‐A are valuable diagnostic tools to characterize pigment epithelium and choroidal changes in PPE eyes.

Are choroidal vascularity parameters influenced by age, hypertension and visual acuity in pachychoroid spectrum diseases?

AbstractPurpose: To identify correlations of subfoveal choroidal thickness (SFCT) and choroidal vascularity index (CVI) with age and best corrected visual acuity in eyes with pachychoroid spectrum diseases (PSD) and their association to systemic hypertension using a retrospective study design.Methods: Our study included 82 eyes of 45 patients with PSD: 15 eyes had uncomplicated pachychoroid (UCP), 27 had pachychoroid pigment epitheliopathy (PPE), 32 had central serous chorioretinopathy (CSC) and 8 had pachychoroid neovasculopathy (PNV). All patients underwent DRI TRITON Swept‐Source Optical Coherence Tomography (SS‐OCT). A 1500 mm width subfoveal choroidal area was defined in SS‐OCT B‐scans and divided into luminal area (LA) and stromal area (SA) by the imageJ binarization technique. CVI was defined as the ratio of LA to the total subfoveal choroidal area (TCA).Results: The mean SFCT was 393, 23 ± 95, 65 μm and it was correlated negatively with age (p = 0.003, R = −0.326). We found a negative correlation of TCA and LA with age (p = 0.043, r = −0.227, p = 0.04, r = −0.230). Mean choroidal vascularity index was 64.45 ± 2, 74% with no correlation with age (p = 0.169, R = −0.155). No parameter among SFCT, CVI, TCA, LA and SA had a significant correlation with BCVA or spherical equivalent. Patients with essential hypertension were found to have significantly thinner SFCT when compared with healthy controls (374, 49 ± 83 141 μm vs. 423, 98 ± 130 466 μm, p = 0.046). CVI was not affected by a history of systemic hypertension (64.05 ± 1.97 vs. 64.83 ± 3.3, p = 0.207). The total choroidal area, luminal area, and stromal area, as well as the CVI correlated with SFCT (p &lt; 0.001, r = 0.817, p &lt; 0.001, r = 0.821, p &lt; 0.001, r = 0.750 and p &lt; 0.001, r = 0.371 respectively).Conclusions: SFCT and CVI are dynamic parameters that are affected in patients with pachychoroid diseases. Unlike CVI, SFCT is also affected by age, ocular and systemic factors like hypertension. CVI may be a more specific biomarker for PSD.

Hyper- and hypo-perfusion of choriocapillaris in the eyes with pachychoroid pigment epitheliopathy.

To evaluate the changes in choriocapillaris vessel density (VD) in eyes with pachychoroid pigment epitheliopathy (PPE) using swept-source optical coherence tomography (OCT) angiography (OCTA). This study included 83 eyes with PPE and 42 control eyes. We collected OCT and OCTA parameters, including central point thickness, subfoveal choroidal thickness (SFChT), and choriocapillaris VD of the fovea (CC fovea) and parafovea. The parafoveal area was divided into superior, nasal, inferior, and temporal choriocapillaris areas. Maximum (CC max) and minimum (CC min) choriocapillaris VD were defined as the highest and lowest values among the four parafoveal subfield VDs, respectively. We analyzed the average choriocapillaris VD, CC max, CC min, CC fovea, and the difference between CC max and CC min (CC delta) individually and compared all the parameters between PPE and control eyes. CC max (56.0% ± 1.7%) was significantly higher and CC min (50.9% ± 2.0%) significantly lower in eyes with PPE than in control eyes (CC max, 55.3% ± 1.0%, P = 0.006; CC min, 51.5% ± 1.3%, P = 0.046). The CC delta value (5.0% ± 2.1%) and SFChT (389.9 ± 129.9μm) were also significantly higher in eyes with PPE than in the control group (3.7% ± 1.5%, P < 0.001; 268.2 ± 102.2μm, P < 0.001; respectively). Choriocapillaris VD showed higher variability (hyperperfusion and hypoperfusion) in eyes with PPE than in control eyes. Choriocapillaris hypoperfusion may precede the development of PPE; however, choriocapillaris hyperperfusion is associated with projection artifacts.

Pachychoroid Disease

Pachychoroid spectrum disorders include uncomplicated pachychoroid, pachychoroid pigment epitheliopathy, central serous chorioretinopathy, pachychoroid neovasculopathy, polypoidal choroidal vasculopathy/aneurysmal type 1 neovascularisation, focal choroidal excavation and peripapillary pachychoroid syndrome. They are characterized by a thickened and hyperpermeable choroid and thinning of the choriocapillaris. The disorders are being diagnosed with increasing frequency and differentiation due to the advancement of multimodality imaging. Current understanding of the development, course, possible complications and treatment of these diseases is growing rapidly, but not all mechanisms have yet been elucidated. A correct diagnosis is important, especially the differentiation between the presence of active neovascularisation or a purely exudative stage, in order to initiate a therapy. It is also not yet clear why patients have a thickened choroid and why some of these patients develop pathological changes such as subretinal fluid, RPE changes or neovascularisation.

Early Stages of Age-Related Macular Degeneration: Racial/Ethnic Differences and Proposal of a New Classification Incorporating Emerging Concept of Choroidal Pathology

The progression of age-related macular degeneration (AMD) is determined by environmental and genetic factors, and phenotypic or molecular risk factors have been investigated extensively. Interestingly, risk factor profiles for advanced AMD differ among individuals, and one of the causes of variation may be explained by their ethnic background. Recent advances in retinal imaging technology have led to the identification of previously unrecognized risk factors for advanced AMD on optical coherence tomography (OCT) and OCT angiography, which expands the concept of traditional imaging risk factors such as drusen and pigmentary abnormalities visible on color fundus photographs. This OCT imaging modality has identified novel pathognomonic changes for early AMD, including the associated photoreceptor, retinal pigment epithelium, and underlying choroidal changes. Regarding features of multimodal imaging associated with the presence or progression of geographic atrophy, there is an international expert consensus classification system; however, features associated with the progression of macular neovascularization (MNV) are still obscure. To make a consensus towards understanding features associated with the risk of MNV, this review focuses on the early stages of AMD by summarizing imaging characteristics and early signs and classifications in view of advanced multimodal imaging technology. Recent evidence suggests that neovascular AMD is not a single disease entity but a heterogeneous disease characterized by MNV. Besides drusen, OCT features associated with pigment abnormalities, such as shallow irregular RPE elevation (SIRE, also known as double-layer sign), pachychoroid pigment epitheliopathy, and choriocapillaris ischemia, seem to confer a high risk of MNV developing, especially for Asian populations.

Ocular findings in asymptomatic patients with primary antiphospholipid syndrome.

Primary antiphospholipid syndrome (PAPS) is characterized by the presence of antiphospholipid antibodies (aPL), repetitive fetal loss, and arterial/venous thrombosis and no association with other autoimmune rheumatic disease. Ocular involvement can also occur including retinal vascular thrombosis and neuro-ophthalmological manifestations, such as optic neuropathy and amaurosis fugax. Early detection of ocular changes is crucial to minimize functional loss. To perform a multimodal evaluation, including the use of Optical Coherence Angiotomography (OCTA), in patients with PAPS without ocular complaints and compare with healthy individuals. We performed a complete structural and functional ophthalmological evaluation using OCTA and microperimetry exam in patients with PAPS, followed at a tertiary Rheumatology outpatient clinic. We included 104 eyes of 52 subjects [PAPS without ocular complaints (N = 26) and healthy individuals (N = 26)]. Among PAPS patients, 21 were female (80.8%) and 21 (80.8%) were Caucasians. PAPS manifestations were venous (65.4%), arterial thrombosis (34.6%), and obstetrical (34.6%) and all of them had lupus anticoagulant. Ophthalmologic findings were more frequent in PAPS compared to healthy individuals (19.2% vs. 0%, p = 0.05). The most common retinal change was paracentral acute middle maculopathy (PAMM) (3 patients, 5 eyes), followed by drusen (1 patient, 2 eyes) and pachychoroid pigment epitheliopathy (PPE) (1 patient, 1 eye). Hypertension and hyperlipidemia were present in 100% of the PAPS patients with PAMM, while only six patients (26.1%) with PAPS without PAMM presented these two risk factors together (p = 0.03). We provide novel evidence that approximately 20% of our asymptomatic PAPS patients without ocular symptoms have ophthalmologic findings that require early identification and careful surveillance focusing on minimizing systemic and vascular risk factors.

Differentiating a pachychoroid and healthy choroid using an unsupervised machine learning approach

The purpose of this study was to introduce a new machine learning approach for differentiation of a pachychoroid from a healthy choroid based on enhanced depth-optical coherence tomography (EDI-OCT) imaging. This study included EDI-OCT images of 103 eyes from 82 patients with central serous chorioretinopathy or pachychoroid pigment epitheliopathy, and 103 eyes from 103 age- and sex-matched healthy subjects. Choroidal features including choroidal thickness (CT), choroidal area (CA), Haller layer thickness (HT), Sattler-choriocapillaris thickness (SCT), and the choroidal vascular index (CVI) were extracted. The Haller ratio (HR) was obtained by dividing HT by CT. Multivariate TwoStep cluster analysis was performed with a preset number of two clusters based on a combination of different choroidal features. Clinical criteria were developed based on the results of the cluster analysis, and two independent skilled retina specialists graded a separate testing dataset based on the new clinical criteria. TwoStep cluster analysis achieved a sensitivity of 1.000 (95-CI: 0.938–1.000) and a specificity of 0.986 (95-CI: 0.919–1.000) in the differentiation of pachy- and healthy choroid. The best result for identification of pachychoroid was obtained for a combination of CT, HR, and CVI, with a correct classification rate of 0.993 (95-CI: 0.980–1.000). Based on the relative variable importance (RVI), the cluster analysis prioritized the choroidal features as follows: HR (RVI: 1.0), CVI (RVI: 0.87), CT (RVI: 0.70), CA (RVI: 0.59), and SCT (RVI: 0.27). After performing a receiver operating characteristic curve analysis on the cluster membership variable, a cutoff point of 389 µm and 0.79 was determined for CT and HR, respectively. Based on these clinical criteria, a sensitivity of 0.793 (95-CI: 0.611–0.904) and a specificity of 0.786 (95-CI: 0.600–0.900) and 0.821 (95-CI: 0.638–0.924) were achieved for each grader. Cohen's kappa of inter-rater reliability was 0.895. Based on an unsupervised machine learning approach, a combination of the Haller ratio and choroidal thickness is the most valuable factor in the differentiation of pachy- and healthy choroids in a clinical setting.