Chiara Mapelli

Corneal Involvement in Rheumatoid Arthritis: An In Vivo Confocal Study

PURPOSE To analyze the in vivo morphology of corneal cells and nerves in patients with rheumatoid arthritis (RA), with or without secondary Sjögrens syndrome (SSII), and to investigate the correlations between corneal alterations and RA activity. METHODS Fifty patients with RA and 30 age- and gender-matched control subjects were studied. SSII was diagnosed according to the American-European Consensus Group criteria, and RA activity was evaluated by the Lansbury index (LI). Confocal microscopy was used to investigate corneal thickness, the number of epithelial and stromal cells, and keratocyte hyperreflectivity. In addition, the sub-basal plexus was assessed for the number, tortuosity, and reflectivity of the nerve fibers and the presence of beadlike formations. RESULTS Sixteen percent of patients with RA also had SSII. Between the SSII and non-SSII groups, no significant differences were found in the LI or in the clinical and confocal variables. Significant differences were present between patients with RA and control subjects for all the variables studied except nerve reflectivity. In patients with RA with and without SSII, LI correlated significantly with the number of beadlike formations and the number of hyperreflective, activated keratocytes. CONCLUSIONS Confocal microscopy of patients with RA showed several changes in corneal cells and nerves. The number of beadlike formations and the number of activated keratocytes could be interpreted as confocal signs of ocular surface disease activity. These correlations with the index of systemic disease activity, LI, may provide insight regarding the pathogenic mechanisms of dry eye in patients with RA.

Choroidal granulomas visualized by enhanced depth imaging optical coherence tomography.

Purpose: To assess the visualization of choroidal granulomas (CG) by enhanced depth imaging optical coherence tomography (EDI-OCT) and to describe their EDI-OCT characteristics. Methods: Combined indocyanine green (ICG) angiography and EDI-OCT images of 44 CG (sarcoid, tubercular, or Vogt–Koyanagi–Harada related) were reviewed. By ICG angiography, CG were classified as full thickness or partial thickness and as small or large. Two independent operators evaluated EDI-OCT scans over granulomas to record their characteristics (full thickness/partial thickness, shape, reflectivity, internal pattern, margins, and shadowing/increased transmission effect). The agreement between ICG angiography and EDI-OCT, the interobserver agreement, and the correlations between EDI-OCT features and lesion size or disease were studied. Results: Enhanced depth imaging optical coherence tomography could visualize 100% of CG detected on ICG. Lesions resulted full thickness in 90.9% and 77.3% of the cases on ICG angiography and EDI-OCT, respectively (K = 0.5). All CG were more homogeneous and showed increased transmission of the optical coherence tomography signal as compared with the surrounding choroid. Choroidal granulomas angiographic size influenced lesions characteristics on EDI-OCT. Large granulomas were more likely to be full thickness, round shaped, with defined margins, lower reflective than the surrounding structures, and with internal homogenous pattern. The type of disease significantly influenced CG shape and pattern. Most of tubercular-related lesions showed lobulated shape and nonhomogeneous internal pattern. Conclusion: Enhanced depth imaging optical coherence tomography is suitable to visualize CG and to describe their characteristics. Choroidal granulomas size and disease influence lesions appearance on EDI-OCT. Increased transmission effect could be helpful for CG identification.

Choroidal Findings in Dome-Shaped Macula in Highly Myopic Eyes: A Longitudinal Study

PURPOSE To describe choroidal findings in dome-shaped macula associated with high myopia using fluorescein angiography (FA), indocyanine green angiography (ICGA), and spectral-domain optical coherence tomography (SD OCT), and to elucidate the mechanism and natural course of serous retinal detachment (RD) associated with dome-shaped macula. DESIGN Retrospective, observational case series. METHODS We reviewed longitudinal imaging results of 52 highly myopic eyes with dome-shaped macula. Changes on FA and ICGA were assessed. Retinal, choroidal, and scleral thicknesses and bulge height were measured on SD OCT. RESULTS Serous RD was the most common abnormality associated with dome-shaped macula, detected by SD OCT in 44% of the cases with no associated choroidal neovascularization. Significant differences in the proportion of eyes with pinpoint leakage on FA (P < .001), punctate hypercyanescence on ICGA (P < .001), and pigment epithelium detachment on SD OCT (P < .001) were noted inside the inward bulge of the staphyloma between eyes with and without serous RD. Serous RD was not associated with hyperpermeability areas on ICGA. Eyes with serous RD had thicker choroid (P = .004) and tended to have thicker sclera (P = .067) and greater bulge height (P = .079). Choroidal thickness, scleral thickness, and bulge height were positively correlated (P < .01). All eyes presented a fluctuating course of serous RD during follow-up. Worsening of serous RD was associated with appearance of new punctate hypercyanescent spots on ICGA and leaking points on FA (P < .001 and P = .016, respectively). CONCLUSION Serous RD in dome-shaped macula was likely caused by choroidal vascular changes, similar to central serous chorioretinopathy, but specifically confined in the inward bulge of the staphyloma and secondary to excessive scleral thickening. Serous retinal detachment showed fluctuating changes over time, with alternating active and inactive stages. Angiographic findings in dome-shaped macula suggest the choroid as a target for possible treatment strategies.

Abnormal Fundus Autofluorescence Results of Patients in Long-term Treatment with Deferoxamine

PURPOSE To describe and classify patterns of abnormal fundus autofluorescence (FAF) of patients with β-thalassemia receiving long-term treatment with deferoxamine (DFO). DESIGN Prospective, cross-sectional, case-control study. PARTICIPANTS A total of 197 consecutive patients with β-thalassemia major or intermedia with at least 10 years of treatment with DFO were recruited in a tertiary referral center in Milan, Italy, and were investigated. Seventy-nine thalassemic patients without a history of chelation therapy were included as a control group. METHODS All of the patients were investigated using best-corrected visual acuity (BCVA), fundus photography, and FAF imaging by confocal scanning laser ophthalmoscopy (cSLO) and were compared with the control group. MAIN OUTCOME MEASURES Identification of abnormal FAF patterns in thalassemic patients treated with long-term DFO and their progression and relationship with visual function. RESULTS Abnormal FAF not related to other diseases was observed in 18 of the 197 patients (9%) and was classified into 4 phenotypic patterns: minimal change, focal, patchy, and speckled. The abnormal increased or decreased FAF was bilateral in all the cases, and only in some cases did it correspond to funduscopically visible alterations. There were no FAF abnormalities in the control group. During the follow-up, progressive FAF changes related to retinal pigment epithelium (RPE) damage occurred in the patchy pattern, associated with decreasing BCVA. Patients with speckled and focal patterns showed limited or no changes in FAF during the follow-up. No changes in FAF were found in patients with a minimal change pattern. No treated patient with a normal baseline examination demonstrated FAF changes. Patients with patterns other than the minimal change showed significant BCVA deterioration (P<0.001). CONCLUSIONS Various phenotypic patterns of abnormal FAF can be identified with cSLO imaging. Fundus autofluorescence is a helpful, fast, and noninvasive tool for monitoring the status of the macula in patients at risk of DFO toxicity. It may be useful in the decision to discontinue or switch the therapy in cases of particular high risk for disease progression. The progressive alteration of the RPE suggests an important role of pathologic RPE changes in the evolution of visual loss during long-term treatment with DFO.

Choroidal volume variations during childhood.

PURPOSE We analyzed choroidal volume (CV) variations during childhood using enhanced depth imaging optical coherence tomography, and evaluated its association with age, axial length (AXL), sex, weight, and height. METHODS Imaging studies of the right eyes of 52 healthy children were reviewed and included in this study. Subjects underwent a complete ocular examination and AXL measurement, as well as a raster macular scan using the Heidelberg Spectralis device. The choroid was segmented manually. RESULTS Subjects included 21 males and 31 females, with mean age of 9 years (range, 2-17 years) and mean AXL of 22.8 ± 0.98 mm. Mean CV was 0.263 ± 0.068 mm(3) for the foveal circle and 8.545 ± 1.822 mm(3) for the total Early Treatment of Diabetic Retinopathy Study (ETDRS) grid. The CV of the nasal quadrant was significantly lower than all others (P < 0.001). Total and foveal CV showed significant negative correlation with AXL after adjustment for age (P < 0.001), and significant positive correlation with age after adjustment for AXL (P < 0.001). Total CV was correlated significantly with sex after adjusting for AXL (P = 0.01), while no correlations were found between total CV and height or weight. The CV increased by 0.214 mm(3) (2.5%) for every year, and decreased by 1.0 mm(3) (11.7%) for every millimeter of axial length. Regression analysis confirmed a trend of higher CV in females than in males (P = 0.056). CONCLUSIONS The CV increases with age during childhood, but decreases with AXL. This finding supports the hypothesis that the choroid grows progressively during childhood. Intersexual differences of CV also may be present.

Multimodal imaging in deferoxamine retinopathy.

Purpose: To describe macular lesions in patients with deferoxamine (DFO) retinopathy, and to follow their clinical course using multimodal imaging. Methods: The authors retrospectively reviewed charts and multimodal imaging of 20 patients with &bgr;-thalassemia diagnosed with DFO retinopathy (40 eyes) after a minimum of 10 years of DFO treatment. Imaging included fundus photography, near-infrared reflectance and fundus autofluorescence imaging on confocal laser scanning ophthalmoscope, and spectral domain optical coherence tomography. Results: Mean age of the 20 patients was 45 years, and mean duration of subcutaneous DFO therapy was 32 years (range, 20–52 years). Ten patients (50%) showed different types of pattern dystrophy–like fundus changes, including butterfly shaped–like (n = 3), fundus flavimaculatus–like (n = 3), fundus pulverulentus–like (n = 3), and vitelliform-like (n = 1) changes. Ten patients (50%) presented only minimal changes in the macula; these patients were significantly younger than patients presenting other patterns (P = 0.023). Confocal laser scanning ophthalmoscope and spectral domain optical coherence tomography showed that these abnormalities were more diverse and widespread than expected by ophthalmoscopy. Abnormal fundus autofluorescence and/or near-infrared reflectance signals corresponded to accumulation of material located within the outer retina or in the Bruch membrane–retinal pigment epithelium (RPE) complex on spectral domain optical coherence tomography. Follow-up examinations during a 40-month period revealed progressive development of RPE atrophy in areas of pattern dystrophy–like changes. Conclusion: DFO retinopathy included a variety of pattern dystrophy–like changes or minimal changes affecting the RPE–Bruch membrane–photoreceptor complex. Multimodal imaging demonstrated that fundus changes were more diverse and widespread than expected from ophthalmoscopy. Consistently with previous histologic description of DFO retinopathy, multimodal imaging confirmed that photoreceptor outer-derived retinoids, various fluorophores, and RPE displacement or clumping are involved in DFO retinopathy, finally leading to frank RPE atrophy in most cases of pattern dystrophy–like changes.

LONGITUDINAL FOLLOW-UP OF CHOROIDAL GRANULOMAS USING ENHANCED DEPTH IMAGING OPTICAL COHERENCE TOMOGRAPHY

Purpose: To assess the ability of enhanced depth imaging optical coherence tomography (EDI-OCT) in detecting variations in the structure and size of choroidal granulomas in response to treatment and to compare these findings with indocyanine green angiography (ICGA). Methods: EDI-OCT and ICGA images of choroidal granulomas in eyes of patients diagnosed with tubercular or sarcoid uveitis were obtained at baseline and follow-up visits. Two independent masked observers analyzed the lesions to compare changes in their structural features such as shape, reflectivity, and margins, among others, through time. The size of each lesion was manually measured on EDI-OCT and ICGA images at all the visits. In addition, longitudinal assessment of choroidal area was performed on the EDI-OCT images during the course of follow-up. Results: Twenty-eight granulomas (16 tubercular and 12 sarcoid; 7 patients) were included in the study. Using EDI-OCT, significant decrease in the mean size of lesions could be appreciated after 1 month of treatment (0.29 mm2 at baseline vs. 0.18 mm2 at 1 month; P < 0.001). However, ICGA did not reveal significant decrease in lesion size at 1 month compared with baseline (0.94 vs. 0.76 mm2; P = 0.07). The granulomas followed a characteristic healing pattern in which the antero-posterior extent (depth) decreased first, followed by decrease in their lateral extent. Apart from size, the choroidal granulomas did not show significant changes in their morphological features on EDI-OCT with treatment. Conclusion: EDI-OCT may be more sensitive than ICGA in detecting early variations in the size of choroidal granulomas. Morphometric analyses of choroidal granulomas on EDI-OCT may be very useful in monitoring the response to treatment in patients with choroidal granulomas.

Bilateral juvenile choroidal neovascularization associated with Best's vitelliform dystrophy: observation versus photodynamic therapy.

The authors recently observed a boy with bilateral choroidal neovascularization associated with Bests disease and compared the outcome of photodynamic therapy in one eye with the natural history of the untreated fellow eye. The final outcome of photodynamic therapy was inactive choroidal neovascularization, which seemed to be enveloped by the retinal pigment epithelium. The final appearance of the treated lesion was similar to the natural evolution of choroidal neovascularization in the untreated fellow eye.

Sequential combined treatment with intravitreal bevacizumab and photodynamic therapy for retinal angiomatous proliferation

PurposeTo study visual and anatomical outcomes of sequenced combined therapy using intravitreal bevacizumab followed by photodynamic therapy (PDT) in eyes with retinal angiomatous proliferation (RAP). Safety and rate of intravitreal injections were also evaluated.MethodsWe conducted a prospective non-comparative pilot study of consecutive patients newly diagnosed with RAP. PDT guided by indocyanine green (ICG) angiography was applied 8±2 days after the intravitreal bevacizumab (1.25 mg) injection. At baseline and every month after the injection, best-corrected visual acuity (BCVA) measurement, complete eye examination including dynamic fluorescein and ICG angiography, and optical coherence tomography (OCT) were performed.ResultsIn all, 21 eyes of 18 patients with RAP were enrolled. The mean age was 77 (range 65–86) years. Mean visual acuity at baseline was 0.63±0.25 logMAR. After treatment BCVA showed no statistically significant differences between each visit (P=0.10, ANOVA). At 9 months, the BCVA improved by three or more lines in three eyes (14%), remained stable in twelve eyes (57%), and worsened in six eyes (29%). Foveal thickness decreased significantly between baseline and all the follow-up visits (P<0.01, ANOVA). A total of 36 intravitreal injections were given during the study with a mean of 1.7 injections per eye (range 1–3 injections per eye). No ocular or systemic adverse events were reported.ConclusionA possible synergistic effect may arise from the combination of intravitreal bevacizumab with PDT for the treatment of RAP. These findings also suggest a possible benefit of combo therapy in the rate of intravitreal re-injections.

Estimated glomerular filtration rate by serum cystatin C correlates with cardiometabolic parameters in patients with primary hyperparathyroidism.

OBJECTIVE Patients with primary hyperparathyroidism (PHPT) are at risk of chronic kidney disease (CKD). Cystatin C (Cys-C) is considered a more reliable tool to assess glomerular filtration rate (GFR) than creatinine. The study aimed to assess circulating Cys-C and its relationships with biochemical PHPT and cardiometabolic parameters. DESIGN AND METHODS The present cross-sectional study was performed in academic endocrine units on PHPT patients (n=190) and non-hypertensive, non-diabetic, age- and sex-matched healthy controls (n=135) with no established CKD. The main outcomes were creatinine by alkaline picrate method, Cys-C by immunonephelometry and calculation of estimated GFR based on creatinine and Cys-C (eGFRcr-cys) using the CKD-EPI equation. RESULTS In PHPT patients, circulating Cys-C ranged 0.45-3.13  mg/l and correlated with creatinine, age and BMI. Mean Cys-C level was higher in PHPT patients than in controls (0.93±0.02 vs 0.78±0.14  mg/l; P=0.03). Cys-C levels in PHPT patients were predicted by age, BMI, ionized calcium, hypertension and HDL-cholesterol, the most significant determinant being ionized calcium. Cys-C positively correlated with cardiovascular disease (CVD) occurrence. Overall, 18.4% of PHPT patients with eGFRcr >60  ml/min per 1.73  m(2) (n=169) had Cys-C levels higher than the 95th percentile in controls (1.03  mg/l), consistent with a preclinical CKD, which was associated with hypertension and insulin resistance. Considering eGFRcr-cys, CKD (stages G3a, G3b, 4) was diagnosed in 13.7% of PHPT patients. Estimated GFRcr-cys, but not eGFR based on creatinine, was predicted by insulin resistance and hypertension and positively correlated with CVD. CONCLUSIONS Elevated Cys-C levels were associated with ionized calcium, cardiometabolic risk factors and CVD, and identified preclinical CKD in PHPT patients.