Choroidal and central foveal thickness in patients with scleroderma and its systemic associations

Esen E., Tas D.A., Sizmaz S., Turk I., Unal I., Demircan N.

Coşkun E., Zengin O., Kenan S., Kimyon G., Erdogan Er K., Okumus S., Mesut Onat A., Erbagcı I., Kısacık B.

To investigate the choroidal thickness in patients with scleroderma and to compare them with healthy control subjects. Forty-six patients with scleroderma (3 male and 43 female) and 31 healthy controls (6 male and 25 female) were included in the study. Twenty-five patients had limited-type and 21 patients had diffuse-type scleroderma. Only left eyes of the patients and control subjects were used in the analysis. Demographic features of all the patients and control subjects were recorded. Each subject underwent ophthalmological examinations including refraction, visual acuity, intraocular pressure, axial length (AXL) measurement, slit-lamp biomicroscopy, and fundus examination. Body mass index (BMI) was estimated for all participants. There were no significant differences between the patients with scleroderma and the control subjects in terms of age, gender, BMI, mean AXL, and mean spherical equivalent refractive error (SE) (P=0.1, P=0.086, P=0.37, P=0.55, and P=0.072 respectively). The patients with scleroderma had significantly thinner nasal, temporal, and subfoveal choroid than the healthy control subjects (P1=0.012, P2=0.046, and P3<0.001, respectively). There were no significant differences between the patients with limited-type and diffuse-type scleroderma in terms of age, gender, BMI, mean AXL, mean SE, nasal, temporal, and subfoveal choroidal thicknesses (all P>0.05). Choroidal thickness in patients with scleroderma was significantly less than healthy control subjects. Vasculopathy in scleroderma is characterized by obliteration of arterioles and reduced capillary density may cause atrophy of choroid in patients with scleroderma.

Ingegnoli F., Gualtierotti R., Pierro L., Del Turco C., Miserocchi E., Schioppo T., Meroni P.L., Gagliardi M., Modorati G., Querques G.

Raynaud's phenomenon (RP) is a reversible vasospastic response of the extremities to cold or emotion, and can be the first manifestation or may be present before the development of an overt systemic sclerosis (SSc). The disturbance of the balance between vasodilation and vasoconstriction is not limited to the peripheral microcirculation of the skin, but it is also observed in other organs, such as the choroidal plexus of the eye. We aimed to examine the choroidal thickness (CT), the macular thickness and ganglion cell complex (GCC) average in thirty consecutive patients, without visual symptoms, classified as primary RP (pRP), RP secondary to suspected SSc, and overt SSc. All the patients underwent rheumatologic and ophthalmologic examination, capillaroscopy, test for anti-nuclear antibodies, anti-dsDNA, and anti-extractable nuclear antigens. Ophthalmologic examination included: best corrected visual acuity; slit lamp biomicroscopy; intraocular pressure measurements, fundus examination, and Spectral Domain-Optical Coherence Tomography (SD-OCT) with enhanced depth imaging scan system. Twenty-seven healthy subjects similar for gender and age were analyzed. In pRP, CT was significantly thinner than controls in the outer nasal and temporal regions. In secondary RP, the inner and outer nasal areas were significantly thinner than controls. In SSc, the central, inner inferior, inner nasal, inner superior, outer temporal, outer inferior, and outer nasal regions were significantly thinner than controls. A decreasing trend of central foveal thickness was noted. All the patients had GCC average significantly lower than controls. A thinning of choroidal and macular thickness, as well as of GCC was observed in patients with pRP and becomes more severe and extensive in RP secondary to suspected SSc and overt SSc. To our knowledge, this is the first study to analyze the choroidal features using SD-OCT in RP. These data may be clinically useful in suggesting an early involvement of ocular microcirculation with significant reduction of choroidal perfusion. • Impairment of ocular microcirculation is a feature of systemic sclerosis. • Subfoveal choroidal thickness is decreased since early phase of systemic sclerosis. • SD-OCT is a non-invasive tool for monitoring ocular microvascular involvement. • Ganglion cell complex average is significantly decreased in systemic sclerosis.

Ulaş F., Çelik F., Doğan Ü., Çelebi S.

Matucci-Cerinic M., Kahaleh B., Wigley F.M.

Kim M., Kim S.S., Kwon H.J., Koh H.J., Lee S.C.

To investigate the correlation of choroidal thickness (CT) with ocular perfusion pressure (OPP) in young, healthy subjects using enhanced depth imaging optical coherence tomography (EDI-OCT).A single horizontal section and a single vertical section of EDI-OCT scans in each eye of 69 young, healthy subjects were obtained at the macula. CT was measured at the fovea, and up to 3 mm, at intervals of 0.5 mm, away from the fovea in the superior, inferior, nasal, and temporal choroid. Univariable and multivariable analyses were performed to assess the association of CT with OPP while axial length (AL), refractive error (RE), sex, and/or body mass index (BMI), were taken into consideration.Mean subfoveal CT was 307.03 ± 91.27 μm (mean age, 22.3 ± 3 years; mean axial length, 25.35 ± 1.14 mm; mean refractive error, -3.89 ± 2.02 diopters; mean OPP, 44.18 ± 5.49 mm Hg). Multivariable regression analysis showed that in eyes with 6 diopters, subfoveal CT (225.17 ± 49.37 μm) was significantly thinner (P < 0.0001), and a significant correlation with OPP was not observed (P > 0.05).In vivo subfoveal CT as measured by EDI-OCT was significantly associated with OPP in young, healthy subjects when adjusted for RE, suggesting that subfoveal CT may be indirectly indicative of subfoveal ocular perfusion status. This association was not observed in subjects with high myopia.

Branchini L., Regatieri C.V., Flores-Moreno I., Baumann B., Fujimoto J.G., Duker J.S.

To investigate the reproducibility of choroidal thickness measurements in normal subjects on 3 spectral domain optical coherence tomography (SD-OCT) instruments: Zeiss Cirrus HD-OCT (Carl Zeiss Meditec Inc., Dublin, CA), Heidelberg Spectralis (Heidelberg Engineering, Heidelberg, Germany), and Optovue RTVue (Optovue Inc., Fremont, CA).Cross-sectional non-interventional study.Images were obtained in 28 eyes of 28 healthy undilated volunteers without ocular pathology in a clinical setting.All subjects were imaged on the fovea using Cirrus HD 1-line raster, Spectralis enhanced depth imaging (EDI), and RTVue retina-cross.The choroid was measured subfoveally, 750 μm temporal, and 750 μm nasal to the fovea. All measurements were performed by 2 independent observers. Two-way analysis of variance (ANOVA) with Bonferroni's post-test, Pearson correlation, and Bland-Altman analysis were used to compare measurements.The group of 28 subjects consisted of 7 men and 21 women, with an average age of 35.2 years (range, 23-64 years). A 2-way ANOVA with Bonferroni's post-test revealed no significant difference in the average subfoveal choroidal thickness (P > 0.05) among systems for any location: subfoveally, 750 μm temporal, and 750 μm nasal to the fovea. The measurements of choroidal thickness from any pair of 3 instruments (Cirrus vs. Spectralis, Cirrus vs. RTVue, Spectralis vs. RTVue) were also strongly correlated. The Pearson correlation among all 2 system pairs of the 3 systems was greater than 0.9 (P < 0.0001). The 95% limits of agreement among 4 choroidal thickness measurements were +11.21% to -13.57% (bias -1.17) between Cirrus and RTVue, +10.85% to -12.45% (bias -0.80) between Spectralis and RTVue, and +12.81% to -13.33% (bias -0.25) between Cirrus and Spectralis.In our population of young healthy adults with normal vision, there was good reproducibility among choroidal thickness measurements of images acquired with Cirrus, Spectralis, and RTVue.Proprietary or commercial disclosure may be found after the references.

Rabquer B.J., Koch A.E.

Systemic sclerosis (scleroderma [SSc]) is a multifactorial disease characterized by inflammation, extensive and progressive fibrosis, and multiple vasculopathies. The vascular manifestations can be seen early in the pathogenesis of the disease and include malformed capillaries, Raynaud’s phenomenon, and digital ulcers. As the disease progresses, the vasculopathy proceeds to significant clinical manifestations, including renal crisis and pulmonary arterial hypertension. Moreover, later stages of the disease are marked by increasingly avascular areas. Despite the obliteration of microvascular structures, compensatory vasculogenesis and angiogenesis do not occur normally. This is in spite of a general increase in many potent angiogenic factors. Recent studies are beginning to examine this paradox and subsequent paucity of an angiogenic response in SSc. In this review, we discuss these findings and examine the role that chemokine and growth factor receptors, proteases, adhesion molecules, and transcription factors play in the dysregulation of angiogenesis in SSc.

Manjunath V., Taha M., Fujimoto J.G., Duker J.S.

To examine choroidal thickness and area in healthy eyes using spectral-domain optical coherence tomography (SD-OCT).Retrospective, observational case series.Thirty-four eyes (34 subjects), with no retinal or choroidal disease, underwent high-definition raster scanning using SD-OCT with frame enhancement software. Choroidal thickness was measured from the posterior edge of the retinal pigment epithelium to the choroid/sclera junction at 500-microm intervals up to 2500 microm temporal and nasal to the fovea. The central 1-mm area of the choroid was also measured, along with foveal thickness of the retina. All measurements were performed by 2 independent observers. Statistical analysis was used to correlate inter-observer findings, choroidal thickness and area measurements with age, and choroidal thickness with retinal foveal thickness.The 34 subjects had a mean age of 51.1 years. Reliable measurements of choroidal thickness were obtainable in 74% of eyes examined. Choroidal thickness and area measurements had strong inter-observer correlation (r = 0.92, P < .0001 and r = 0.93, P < .0001 respectively). Area had a moderate negative correlation with age (r = -0.62, P < .0001) that was comparable to the correlation between mean subfoveal choroidal thickness and age (r = -0.61, P < .0001). Retinal and choroidal thickness were found to be poorly correlated (r = -0.23, P = .18). Mean choroidal thickness showed a pattern of thinnest choroid nasally, thickening in the subfoveal region, and then thinning again temporally. Mean subfoveal choroidal thickness was found to be 272 microm (SD, +/- 81 microm).Choroidal thickness can be measured using SD-OCT high-definition raster scans in the majority of eyes. Choroidal thickness across the macula demonstrates a thin choroid nasally, thickest subfoveally, and again thinner temporally, and a trend toward decreasing choroidal thickness with age.

Margolis R., Spaide R.F.

To measure macular choroidal thickness in normal eyes at different points using enhanced depth imaging (EDI) optical coherence tomography (OCT) and to evaluate the association of choroidal thickness and age.Retrospective, observational case series.EDI OCT images were obtained in patients without significant retinal or choroidal pathologic features. The images were obtained by positioning a spectral-domain OCT device close enough to the eye to acquire an inverted image. Seven sections were obtained within a 5 x 30-degree area centered at the fovea, with 100 scans averaged for each section. The choroid was measured from the outer border of the retinal pigment epithelium to the inner scleral border at 500-microm intervals of a horizontal section from 3 mm temporal to the fovea to 3 mm nasal to the fovea. Statistical analysis was performed to evaluate variations of choroidal thickness at each location and to correlate choroidal thickness and patient age.The mean age of the 30 patients (54 eyes) was 50.4 years (range, 19 to 85 years), and 14 patients (46.7%) were female. The choroid was thickest underneath the fovea (mean, 287 microm; standard deviation, +/- 76 microm). Choroidal thickness decreased rapidly in the nasal direction and averaged 145 microm (+/- 57 microm) at 3 mm nasal to the fovea. Increasing age was correlated significantly with decreasing choroidal thickness at all points measured. Regression analysis suggested that the subfoveal choroidal thickness decreased by 15.6 microm for each decade of life.Choroidal thickness seems to vary topographically within the posterior pole. The thickness of the choroid showed a negative correlation with age. The decrease in the thickness of the choroid may play a role in the pathophysiologic features of various age-related ocular conditions.

Tailor R., Gupta A., Herrick A., Kwartz J.

Systemic sclerosis is a chronic multi-system disorder predominantly affecting the skin, musculoskeletal, gastrointestinal, pulmonary, and renal systems. Although the exact etiology is unknown, recent evidence suggests that immune activation play a pivotal role in the pathogenesis. Ocular involvement in systemic sclerosis has been documented; however, due to the rare nature of the disease, most papers have been single case reports or small case series. This review paper aims to consolidate the findings of previous papers with a view to providing a comprehensive review of the ocular manifestations of systemic sclerosis.

Povazay B., Hermann B., Hofer B., Kajic V., Simpson E., Bridgford T., Drexler W.

To demonstrate high-speed, high axial resolution optical coherence tomography (OCT) at 1060 nm with penetration to the sclera. The clinical feasibility of dense, high-speed sampling for higher levels of detail at the macula and optic nerve head is explored with respect to motion artifacts.A three-dimensional (3D) OCT system making use of a high-speed camera operating at 47,000 depth scans/s was developed. The 1010- to 1080-nm wavelength band leads to 6.7 microm effective axial resolution and enables the acquisition of retinal and choroidal 130 Megavoxel volumes of human subjects within 7 seconds. Motion artifacts were reduced by numeric postprocessing techniques.Drift motion artifacts could be suppressed within fields up to 38 degrees x 38 degrees (approximately 1 cm(2)) using acquisition speeds of up to 74 frames/s at 512 x 512 pixel/frame. This isotropic OCT sampling of the human retina in vivo allowed reconstruction of the retinal microvasculature solely on vessel reflectivity, without the use of contrast agents, and revealed three interconnected capillary meshworks. Simultaneously in the choroid, the structure of the choriocapillaris, Sattler's layer, and Haller's layer were differentiated, and the choroidal-scleral interface was clearly delineated in densely sampled narrow- and wide-angle scans (>38 degrees). At the optic nerve head, the 3D fine structure of the lamina cribrosa and the circle of Zinn-Haller were visualized.OCT almost centered within the 1060-nm water transmission window significantly profits from lower scattering and allows investigation of the retina and choroid at an unprecedented combination of penetration and high speed at high resolution and may provide superior clinical feasibility to commercial 800-nm devices.

Spaide R.F., Koizumi H., Pozonni M.C.

To describe a method to obtain images of the choroid using conventional spectral-domain (SD) optical coherence tomography (OCT) and to evaluate choroidal thickness measurements using these images.Observational case series.The images were obtained by positioning the SD OCT device close enough to the eye to obtain an inverted representation of the fundus in healthy volunteers who did not have pupillary dilation. Seven sections, each comprised of 100 averaged scans, were obtained within a 5- x 15-degree rectangle centered on the fovea. The choroidal thickness under the fovea in each image was measured by independent observers.The choroidal thickness could be evaluated in every subject's choroidal image. The mean choroidal thickness under the fovea was 318 microm in the right eye and 335 microm in the left eye. The choroidal thickness showed a high correlation in both eyes (r = 0.82; P < .001). The correlation between the measurements performed by the independent observers was highly significant (right eye, r = 0.93; left eye, r = 0.97; P < .001 for both).This method provides detailed, measurable images from the choroid, a structure that heretofore has been difficult to image in clinical practice.

Grieshaber M.C., Mozaffarieh M., Flammer J.

The need of blood flow to different organs varies rapidly over time which is why there is sophisticated local regulation of blood flow. The term dysregulation simply means that blood flow is not properly adapted to this need. Dysregulative mechanisms can lead to an over- or underperfusion. A steady overperfusion may be less critical for long-term damage. A constant underperfusion, however, can lead to some tissue atrophy or in extreme situations to infarction. Unstable perfusion (underperfusion followed by reperfusion) leads to oxidative stress. There are a number of causes that lead to local or systemic vascular dysregulation. Systemic dysregulation can be primary or secondary of nature. A secondary dysregulation is due to other autoimmune diseases such as rheumatoid arthritis, giant cell arteritis, systemic lupus erythematodes, multiple sclerosis, colitis ulcerosa, or Crohns disease. Patients with a secondary vascular dysregulation normally have a high level of circulating endothelin-1 (ET-1). This increased level of ET-1 leads to a reduction of blood flow both in the choroid and the optic nerve head but has little influence on autoregulation. In contrast, primary vascular dysregulation has little influence on baseline ocular blood flow but interferes with autoregulation. This, in turn, leads to unstable oxygen supply, which seems to be a relevant component in the pathogenesis of glaucomatous optic neuropathy.

Sakkas L.I.

Lohrasbi F., Karimi E., Gouravani M., fooladi Sarabi S., Mafi A., Beikmarzehei A., Sanjari Moghaddam H., Parsaei M., Tabatabaei S., Arevalo J.F.

Introduction: Optical coherence tomography angiography (OCTA) is an emerging technique to investigate retinal and choroidal microvascular alterations in patients with systemic sclerosis (SSc). This systematic review and meta-analysis aimed to evaluate the features of retinal and choroidal microvasculature using OCTA among SSc patients. Methods: The methodology of the study was based on PRISMA guidelines. PubMed, Scopus, Web of Science, and Embase were searched systematically on November 25, 2023, for relevant studies utilizing OCTA as the main diagnostic tool to assess the retinal and choroidal microvasculature in SSc patients versus healthy controls. Random-effect or fixed model meta-analysis was used based on the heterogeneity of studies. Results: Eleven observational comparative studies, including 366 patients with SSc and 350 healthy controls, conducted between 2020 and 2023, were included in this review. Meta-analysis findings revealed a significant decrease in vessel densities in both the superficial and deep capillary plexuses (SCP and DCP) among SSc patients compared to controls. However, there were no significant differences observed in the foveal avascular zone (FAZ) area and choriocapillary flow area (CCFA) between SSc patients and controls. Moreover, central macular thickness (CMT) consistently exhibited a decrease in SSc patients, while retinal nerve fiber layer (RNFL) thickness showed no significant differences. Although radial peripapillary capillary (RPC) vessel density, subfoveal choroidal thickness (CMT), and cup/disc ratio yielded mixed results, with some studies indicating significant changes in the SSc group, meta-analysis could not be performed due to variations in the OCTA machines used across the included studies. Conclusion: This systematic review demonstrates retinal and choroidal microvascular abnormalities in SSc using OCTA. Longitudinal studies are needed to understand how these abnormalities evolve over time in patients with SSc and whether these abnormalities correlate with the clinical features of SSc.

Paczwa K., Rerych M., Romanowska-Próchnicka K., Różycki R., Gołębiewska J.

Systemic sclerosis (SSc) is a chronic autoimmune connective tissue disease that affects more than 2 million people worldwide. It manifests through vasculopathy, an abnormal immunological response, and fibrosis leading to dysfunction of the multiple organs. The disease is categorized into two subtypes: limited cutaneous SSc and diffuse cutaneous SSc. Scleroderma can affect vital organs with respiratory, cardiac, renal, ocular, and dermatological complications. The ocular manifestations of the disease can occur in the anterior and posterior segments of the eye. Changes in the anterior segment related to the disease include eyelid skin remodeling, dry eye syndrome, and conjunctival abnormalities. The disease’s impact on the posterior segment of the eye mostly causes pathologies in the retinal microcirculatory system and abnormalities in the optic nerve. This review provides detailed insights into ocular complications associated with scleroderma.

Han Y.E., Jo J., Kim H.C., Lee J.

Abstract Background Although choroidal thickening was reported as a sign of active inflammation in ocular sarcoidosis, there has been no research on the choroidal changes in non-ocular sarcoidosis (defined as systemic sarcoidosis without overt clinical signs of ocular involvement). Therefore, this study aimed to investigate choroidal structural changes in patients with non-ocular sarcoidosis. Methods This retrospective case–control study was conducted at Asan Medical Center, a tertiary referral center. We evaluated 30 eyes with non-ocular sarcoidosis and their age- and spherical equivalent-matched healthy control eyes. The subfoveal choroidal thickness, area ratio (Sattler layer-choriocapillaris complex [SLCC] area to Haller layer [HL] area), and choroidal vascularity index (CVI, luminal area to choroidal area) were analyzed using enhanced depth imaging in optical coherence tomography. Systemic and ocular factors associated with the choroidal thickness were investigated. Results Compared with the healthy control group, the non-ocular sarcoidosis group had significantly thicker subfoveal choroid (total and all sublayers [SLCC and HL]) and lower area ratio. There were no significant differences in the CVIs at all sublayers between groups. In the non-ocular sarcoidosis group, eyes under oral steroid treatment had thinner choroid than eyes under observation. In the control group, eyes with older age and more myopic spherical equivalent had thinner choroidal thickness. Conclusion Total and all sublayers of the subfoveal choroid were significantly thicker without significant vascularity changes in non-ocular sarcoidosis eyes than in healthy control eyes. The degree of choroidal thickening was disproportionally greater at HL than at SLCC. These characteristic choroidal changes may be the subclinical manifestations in non-ocular sarcoidosis.

Dönmez Gün R., Tezcan M.E., Özen M.C., Tutaş Günaydın N., Şimşek Ş.

To evaluate anterior and posterior segment parameters in the eyes of patients with systemic sclerosis (SSc) and examine the effect of disease and disease subtypes on these parameters. This cross-sectional study included 54 eyes of 27 SSc patients and 54 eyes of 27 age- and sex-matched healthy controls. In addition to a complete ophthalmologic examination, all patients were examined using a Scheimpflug camera, specular microscopy, and spectral domain optical coherence tomography. The mean age of the patients was 52.5 ± 11.4 years and 19 patients were female. Anterior chamber volume, central corneal thickness, and central macular thickness (CMT) were significantly lower in the eyes of SSc patients compared to healthy controls (p = 0.01, p = 0.03, and p = 0.006, respectively). When evaluated according to SSc subtype, CMT was lower in diffuse SSc patients (p = 0.001), while mean retinal nerve fiber layer (RNFL) and inferior quadrant RNFL values were lower in limited SSc (p = 0.003 and p = 0.005, respectively). In the eyes of patients with SSc, some ocular parameters may show decreases compared to healthy individuals, presumably secondary to disease-related vasculopathy and fibrosis. CMT and RNFL parameters may be affected differently according to disease subtype.

Pieklarz B., Gińdzieńska-Sieśkiewicz E., Zawadzka I., Bagrowska M., Daniluk J., Sidorczuk P., Kowal-Bielecka O., Konopińska J., Dmuchowska D.A.

IntroductionPatients with systemic sclerosis (SSc) present an increased risk of developing glaucomatous optic neuropathy (GON). We investigated peripapillary choroidal parameters and peripapillary retinal nerve fiber layer (RNFL) thickness using spectral domain optical coherence tomography (SD-OCT) to determine the relationships of these factors with clinical variables.MethodsA total of 33 patients with SSc were enrolled and compared to 40 controls. After obtaining circular scans around the optic disc, the global and quadrant peripapillary choroidal thickness (pCT) and RNFL thickness were measured. Additionally, the peripapillary choroidal vascularity index (pCVI), which allows for a quantitative analysis of the choroidal vasculature, was determined.ResultsNo significant differences were found in pCT and RNFL thickness between patients with SSc and controls, or within SSc subtypes (diffuse cutaneous systemic sclerosis (dcSSc) compared to limited cutaneous systemic sclerosis (lcSSc)) (p &gt; 0.05). The pCVI was significantly lower in patients with SSc than in control subjects (64.25 ± 1.94 vs.65.73 ± 2.12, p &lt; 0.001).ConclusionOur results suggest that the statistically significant decrease in pCVI in patients with SSc compared to the control group is probably due to a decrease in the vascular layer, which would partially explain an increased risk of GON in patients with SSc.

Ceri M., Pekel G., Mert M., Bozkurt K., Tas M.Y., Dursun B.

• There is no study has been conducted on an adult nephrotic syndrome (NS) population and ocular changes. This is important because it is the first study to show the effects on ocular changes in NS patients with preserved kidney functions. • In this study, a significant negative correlation was found between creatinine, BUN and CCT. This result showed the importance of including NS patients with preserved renal function, in terms of evaluating the effect of glomerulonephritis on ocular changes alone. • Kidney glomeruli and the choroid have comparable designs and vascular organizations. The results of the current study showed a significant difference between the NS group and the control group in terms of some ocular changes (i.e., CFT and RAC). These results also support the similarity between kidney and eye. • In conclusion, CCT, CFT and RAC measurements with OCT may be used as a marker of inflammation in NS patients. Optical coherence tomography (OCT) measurements of central choroidal thickness (CCT) and retinal thickness have been proposed as inflammatory indicators for a variety of systemic disorders, particularly those with a vascular component. The relationship between nephrotic syndrome (NS) and visual impairment is not clear. The aim of this study was to evaluate the ocular changes in primary NS patients with preserved renal functions. A total of 60 participants (30 NS patients, 30 healthy control subjects) was recruited in this cross-sectional and comparative study. Retinal and choroidal examinations were performed via the spectral domain OCT. Enhanced depth imaging (EDI) mode of the OCT was used for choroidal analysis. Although not statistically significant, CCT was found to be higher in the NS group compared to the control group ( p = 0.07). Central foveal thickness (CFT) and retinal arteriolar caliber (RAC) values were statistically significantly lower in the patients with nephrotic syndrome, whereas retinal venular caliber (RVC) and choroidal vascularity index (CVI) values were similar in both groups. RAC and RVC were not statistically significantly correlated with CCT or CFT in both groups ( p > 0.05). The results of the current study showed a significant difference between the NS group and the control group in terms of some ocular changes (i.e., CFT and RAC). As a result, CCT, CFT and RAC measurements with OCT may be used as a marker of inflammation in NS patients.

Özdal P.Ç., Tugal-Tutkun I.

Systemic vasculitides are a large group of heterogeneous diseases characterized by inflammatory destruction of blood vessels targeting diverse organs and tissues including the eye. As the most vascularized layer of the eye, the choroid is expected to be affected in multiple systemic rheumatologic diseases with vascular involvement. While there are plenty of studies investigating retinal vascular involvement, choroidal vascular involvement in systemic vasculitides has not been investigated in isolation. However, choroidal manifestations including thickness changes, choroidal vasculitis and ischemia may be the earliest diagnostic features of systemic vasculitic diseases. Thus, multimodal imaging of the choroid may help early detection of choroidal involvement which may also have prognostic implications in these life-threatening diseases. This article aimed to review involvement of the choroid in systemic vasculitic diseases.

Küçük M.F., Yaprak L., Erol M.K., Ayan A., Kök M.

To analyze the macular microvascular (MMV) architecture, radial peripapillary capillary (RPC) network and choriocapillaris using optical coherence tomography angiography (OCT-A) in patients with systemic sclerosis (SSc) without systemic comorbidities.The vessel densities (VDs) of the MMV, foveal avascular zone (FAZ) parameters, choriocapillaris flow areas (CCFAs), RPC VDs, and optic nerve head (ONH) parameters were measured by OCT-A. Retinal thickness and subfoveal choroidal thickness (SFCT) were measured by spectral-domain optical coherence tomography (SD-OCT). The SD-OCT and OCT-A measurements of 53 eyes of 30 SSc patients were compared with 61 eyes of 33 healthy controls.In the MMV analysis, a decrease in the VDs of the superficial capillary plexus and an increase in the FAZ area, FAZ perimeter and non-flow area were detected in the SSc group compared to the controls (P=0.007, P=0.001, P=0.029, P=0.018, and P=0.039, respectively). While there was a decrease in SFCT, no change was found in CCFA (P=0.001 and P=0.902, respectively). The RPC analysis revealed a decrease in the VDs of all vessels for the entire area and the intradisc area, as well as the VDs of the small vessels for the intradisc area (P=0.021, P=0.001, and P=0.003, respectively). In the ONH analysis, there was an increase in the C/D area ratios and cup volumes, and a decrease in the rim areas and nasal quadrant retinal nerve fiber layer thickness (P=0.004, P=0.004, P=0.013, and P=0.032, respectively).Decreases in RPC and MMV VDs and changes in ONH parameters were found in OCT-A measurements in patients with SSc.

Karpova D.A., Savina E.E., Ponomareva M.N., Lushpaeva Y.A., Partikeeva I.M.

This literature review is devoted to the analysis of modern insights into ophthalmological manifestations (according to the data of foreign scientific literature in the PubMed system for 20172020) of the most common rheumatic diseases (rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, systemic scleroderma, systemic vasculitis), which are characterized by damage to all structures of the eye and its adnexa: eyelids, orbital tissues, eyeball tunics, vessels, optic nerve and vitreous. Ocular lesion may be an onset, one of the diagnostic signs, or a biomarker of underlying medical condition.

Kaymaz S., Halil Y., Kaya H., Karasu U., Cobankara V.

To evaluate choroidal thickness (CT), corneal parameters, and scleral thickness (ST) in patients with systemic sclerosis (SSc) and to determine their relationship with disease-related quality of life (QoL).The study included 38 patients with SSc and 40 healthy controls. A detailed ocular examination was performed on all participants. Corneal parameters such as K1, K2, Km, corneal volume (CV), central corneal thickness (CCT), and ST at a distance of 1000, 2000, and 3000 μm from the scleral spur were measured. CT was measured at five points, including the subfoveal area and the temporal and nasal points at radii of 750.0 and 1500.0 μm. The scleroderma health assessment questionnaire (SHAQ) was administered to SSc patients to investigate the disease-related QoL.Individuals with SSc had thicker ST at all distances from the scleral spur (P=0.008, P=0.001, P=0.002, respectively). All corneal parameters were significantly lower in the SSc group than in the control group (P < 0.05). Moreover, SSc patients had significantly lower median CT at N750.0, N1500.0, T750.0, and T1500.0 points and thinner subfoveal CT than healthy controls (P < 0.05). There was a weak-moderate negative correlation between ST and the components of the SHAQ scale and SHAQ-global.Despite not having ocular involvement, SSc patients had thicker ST but thinner CT and corneal parameters than healthy controls. This may indicate subclinical inflammation in patients with SSc. Only ST was affected by organ involvement and QoL among the ocular parameters.

Kök M., Ayan A., Fatih Küçük M., Erol M.K., Yaprak L.

Ocular involvement in systemic sclerosis (SSc) has been documented; however it cannot be distinguished from secondary changes due to concomitant hypertension.Therefore, the aim of this prospective cross-sectional study was to demonstrate the direct effects of Ssc on retinal and choroidal microvasculature in patients without hypertension.47 SSc patients and 44 age- and sex-matched healthy control subjects were enrolled in this study. In fundus examination: Increased vascular tortitis, focal or general arteriolar narrowing, arteriovenous notch, severe exudation, microhemorrhage, and pigment epithelial changes in the retina of SSc patients without hypertension were investigated. Patients with at least two of the above findings were considered to have retinopathy After that, patients were divided into two groups according to the presence of retinopathy in this study. Retinal and choroidal microvasculature were evaluated using optical coherence tomography angiography.There was a significant decrease in SSc patients with retinopathy in both superficial capillary plexus vessel density (SCP VD) and deep capillary plexus vessel density (DCP VD) compared to the control group. Full avascular zone (FAZ) evaluation tool variables (FAZ area, FAZ perimeter, foveal density) were significantly lower in all Ssc patients than in the healthy control group. It was found that the flow in the 1 mm and 3 mm circular area (Outer Retina 1-3 mm Flow Area) increased significantly in Ssc patients with retinopathy. Choroidal flow (Choriocapillaries 1 mm Flow Area) was statistically lower in Ssc patients with retinopathy.We have showed an increase in the outer retina 1-3 mm flow area (circular area of the outer retina fold covering the fovea) despite the decrease in vascular density and choroidal thickness in scleroderma patients with retinopathy. Hence, we first demonstrated that Ssc itself may have an effect on retinal and choroidal microvasculature, independent of hypertension.

Casini G., Marinò M., Rubino M., Licari S., Covello G., Mazzi B., Ionni I., Rocchi R., Sframeli A.T., Figus M., Loiudice P.

To compare optic disc, retinal and choroidal measurements in patients with Graves’ disease with or without orbitopathy, and healthy controls. Optical coherence tomography and Heidelberg retinal tomography were performed in 40 patients with Graves’ orbitopathy (GO), 40 subjects with Graves’s disease (GD) with no sign of orbitopathy and 40 healthy controls. Degree of exophthalmos, ocular alignment, clinical activity score (CAS), choroidal thickness, retinal thickness, ganglion cell layer (GCL) thickness, disc area, cup area, rim area, cup/disc area ratio, linear cup/disc ratio and mean peripapillary retinal nerve fibre layer thickness were analysed. GO patients and healthy controls significantly differ regarding mean central retinal thickness (275 ± 19 µm and 285 ± 20 µm, P = 0.017); mean central GCL thickness (14.87 ± 3.0 µm and 17.92 ± 5.02 µm, P = 0.001); mean disc area (2.00 ± 0.44 mm2 and 1.72 ± 0.37 mm2, P = 0.003); mean cup area (0.53 ± 0.52 mm2 and 0.31 ± 0.20 mm2, P = 0.003); cup/disc area ratio (0.22 ± 0.10 and 0.17 ± 0.08, P = 0.010); and linear cup/disc ratio (0.47 ± 0.15 and 0.40 ± 0.13, respectively, P = 0.011). No difference was found between patients without orbitopathy and healthy controls. No significant difference was found regarding the choroidal thickness between the three groups. There was no statistically significant relationship between retinal thickness, ganglion cell layer thickness, mean disc area, mean cup area, cup/disc area ratio, linear cup/disc ratio, CAS, exophthalmometric value and ocular alignment. GO patients showed significant changes in foveal and GCL thickness, and optic nerve head morphology suggesting a possible influence of the orbital inflammatory process.

Steiner M., Esteban-Ortega M.D., Muñoz-Fernández S.

To identify the risk of relapse and subclinical inflammatory stages of systemic autoimmune diseases, new tools are needed. In the recent years, choroidal thickness and retinal thickness measured with ocular coherence tomography (OCT) have been proposed as an inflammatory marker for different systemic diseases, especially for conditions with a vascular component. Our aim in this article is to review the literature regarding the role of choroidal and retinal thickness as a potential inflammatory marker in systemic autoimmune and inflammatory diseases measured by OCT. Current literature suggests that the choroid of patients thickens in active phases of inflammatory diseases with vascular involvement. This pattern is observed in lupus, systemic sclerosis, Behçet disease, spondylitis, and familial Mediterranean fever. Choroidal thickness may decrease with biological treatments, along with systemic inflammation. Repeated flares and long-term disease, however, may thin the choroid, as a result of prolonged insult to the microvasculature and subsequent atrophy. Less is known about the effect of these diseases on retinal thickness. In summary, choroidal and retinal thickness measured by OCT may be promising markers for inflammation in systemic autoimmune and inflammatory diseases; however, more studies are warranted before generalizing choroidal thickness measurements by OCT as a marker for disease activity. The role of retinal thickness is more unclear due to a lack of studies in this field.

Kreps E.O., Carton C., Cutolo M., Cutolo C.A., Vanhaecke A., Leroy B.P., Smith V.

Systemic sclerosis (SSc) is a rare and complex autoimmune disorder characterized by microvascular damage and progressive fibrosis which affects the skin and multiple other organs. Much of the published data concerning SSc and the eye consists of single case reports or small case studies. This systematic review aims to provide an overview of the current level of evidence for SSc-related ocular changes.A systematic literature review was conducted using 3 electronic databases, according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. A combination of following keywords was used: "Systemic Sclerosis" and ophthalmology-related search terms, including the keywords "Eye", "Ocular" and "Ophthalmic". All articles were screened by 2 independent reviewers at title, abstract and full text level. We solely included case-control studies that investigated specific ocular findings in SSc patients compared to healthy controls.Nine of 270 articles were retained. Dry eye symptoms are associated with SSc, whereas objective signs (Schirmer I testing) show conflicting results. There is insufficient evidence of SSc-related changes to the central corneal thickness. In terms of posterior segment involvement, choroidal vasculature appears to be affected to greater extent than the retinal microcirculation. However, the limited number of patients included in the studies renders it hazardous to draw overall conclusions.There is a paucity of well-designed case-control studies investigating possible ocular involvement in SSc. Our systematic review demonstrates limited proven associations between SSc and ocular abnormalities, mainly in terms of dry eye symptoms and choroidal thickness. Future standardized prospective studies are needed to clarify the impact of the disease on the eye.