Mariacristina Parravano

Analysis of retinal capillaries in patients with type 1 diabetes and nonproliferative diabetic retinopathy using adaptive optics imaging.

Purpose: To illustrate a noninvasive method to analyze the retinal capillary lumen caliber in patients with Type 1 diabetes. Methods: Adaptive optics imaging of the retinal capillaries were acquired in two parafoveal regions of interest in eyes with nonproliferative diabetic retinopathy and unaffected controls. Measures of the retinal capillary lumen caliber were quantified using an algorithm written in Matlab by an independent observer in a masked manner. Comparison of the adaptive optics images with red-free and color wide fundus retinography images was also assessed. Results: Eight eyes with nonproliferative diabetic retinopathy (eight patients, study group), no macular edema, and preserved visual acuity and eight control eyes (eight healthy volunteers; control group) were analyzed. The repeatability of capillary lumen caliber measurements was 0.22 &mgr;m (3.5%) with the 95% confidence interval between 0.12 and 0.31 &mgr;m in the study group. It was 0.30 &mgr;m (4.1%) with the 95% confidence interval between 0.16 and 0.43 &mgr;m in the control group. The average capillary lumen caliber was significantly narrower in eyes with nonproliferative diabetic retinopathy (6.27 ± 1.63 &mgr;m) than in the control eyes (7.31 ± 1.59 &mgr;m, P = 0.002). Conclusion: The authors demonstrated a noninvasive method to analyze, with micrometric scale of resolution, the lumen of retinal capillaries. The parafoveal capillaries were narrower in patients with Type 1 diabetes and nonproliferative diabetic retinopathy than in healthy subjects, showing the potential capability of adaptive optics imaging to detect pathologic variations of the retinal microvascular structures in vaso-occlusive diseases.

Influence of Disc Size on Optic Nerve Head versus Retinal Nerve Fiber Layer Assessment for Diagnosing Glaucoma

PURPOSE To explore and compare the influence of optic disc size on the diagnostic accuracy of retinal nerve fiber layer (RNFL) thickness and optic nerve head (ONH) quantitative assessment. DESIGN Observational, cross-sectional evaluation of diagnostic tests. PARTICIPANTS We included 120 eyes from 50 normal subjects and 70 glaucomatous patients classified by the presence of a repeatable visual field defect for the analysis. TESTING The RNFL thickness was measured by scanning laser polarimetry with variable corneal compensator (GDx-VCC, Carl-Zeiss Meditec, Dublin, CA) and spectral-domain optical coherence tomography (Cirrus HD-OCT, Carl Zeiss Meditec, Inc). We obtained ONH imaging by means of confocal scanning laser ophthalmoscopy (HRT3; Heidelberg Engineering, GmbH, Dossenheim, Germany). MAIN OUTCOME MEASURES Sensitivity and specificity for normative classifications, sensitivity at fixed specificity and area under the receiver operating characteristics curve (AUC) for continuous parameters. A logistic marginal regression model and coefficients of variation (CoV) have been used to test and quantify the influence of optic disc size on the diagnostic accuracy of the 3 technologies under investigation. RESULTS Among continuous parameters average RNFL thickness for Cirrus HD-OCT, nerve fiber indicator for GDx-VCC and cup shape measure for the HRT3 showed the best diagnostic accuracy with an AUC of 0.97, 0.94, and 0.94, respectively. Among normative classifications, the highest sensitivity and specificity were found for OCT average RNFL thickness (75.8% and 94.7%), for GDx superior thickness (77.1% and 97.5%), for HRT3 Moorfields regression analysis result (89.4% and 73.7%) and for HRT3 GPS global (92.3% and 76.5%). The diagnostic performance of HRT3 parameters seemed to be significantly influenced by optic disc size, although the same was not true for Cirrus HD-OCT and GDx VCC. The most steady performers for each imaging device across disc size groups were Cirrus HD-OCT average thickness (CoV, 1.6%), GDx-VCC inferior thickness (CoV, 2.5%), and HRT3 GPS temporal and nasal (CoV, 21.4%). CONCLUSIONS The diagnostic accuracy of quantitative RNFL assessment as performed by Cirrus HD-OCT and GDx-VCC is high and virtually unaffected or only minimally affected by the size of the optic disc and may provide more consistent diagnostic outcomes across small and large discs than ONH assessment as performed by HRT3.

Retinal functional changes measured by microperimetry in neovascular age-related macular degeneration treated with ranibizumab: 24-month results.

Purpose: The purpose of this study was to assess long-term functional and structural retinal changes in patients with neovascular age-related macular degeneration treated with intravitreal 0.5 mg ranibizumab. Methods: Eighteen patients with neovascular age-related macular degeneration have been evaluated in this retrospective 24-month follow-up study. All patients have been treated with 3 injections of 0.5 mg ranibizumab 1 month apart and retreated according to predefined criteria. At baseline, all patients were subjected to visual acuity, fluorescein angiography, MP1 microperimetry, and Stratus optical coherence tomography. Although visual acuity and optical coherence tomography were repeated 28 ± 2 days after each injection, MP1 was performed at 6, 12, and 24 months. Results: Seventeen of 18 and 14 of 18 patients completed 12 and 24 months of follow-up, respectively. Mean retinal sensitivity significantly improved from 3.89 ± 3.0 dB to 7.33 ± 4.11 dB at 24 months (P = 0.024). Mean visual acuity improved from 48.67 ± 8.59 to 59.17 ± 16.45 at 24 months (P = 0.049). Visual acuity improved to ≥15 letters in 33.3% (6 of 18) of patients and <15 letters in 44.4% (8 of 18); 22.2% (4 of 18) of patients lost <15 letters at 24 months. Five of 13 patients (38.5%) with either an instable or relatively instable fixation at baseline showed improvement of fixation stability at 24 months. Central retinal thickness significantly decreased from 310.5 ± 85.7 to 232.9 ± 60.1 at 24 months (P = 0.0001). Conclusion: Intravitreal injections of 0.5 mg ranibizumab determine progressive improvement of retinal sensitivity until 24 months, although visual acuity levels off after 6 months, suggesting that microperimetry may give additional information about macular function not given by visual acuity alone.

The role of Humphrey Matrix testing in the early diagnosis of retinopathy in type 1 diabetes

Aim: The aim of the study was to investigate the role of Humphrey Matrix threshold testing in the detection of early functional retinal impairment in subjects with type 1 diabetes mellitus (DM1) without any signs of retinal vasculopathy, and to investigate the relationship between both functional and structural retinal parameters and metabolic control. Methods: Thirty eyes of 30 subjects with DM1, with no sign of retinal vasculopathy, and 30 eyes of 30 age- and sex-matched healthy subjects were enrolled in this cross-sectional clinical study. Functional testing included Humphrey Matrix perimetry and white-on-white Humphrey visual field perimetry (HFA), while retinal nerve fibre layer (RNFL) thickness was measured by scanning laser polarimetry with variable corneal birefringence compensator (GDx VCC). Results: Matrix mean deviation (MD) was found to be significantly reduced in subjects with DM1 compared with controls (−1.10 (SD 2.98; 95% CI −2.21 to 0.01) vs 1.37 (SD 2.11; 95% CI 0.58 to 2.16), p = 0.0005). HFA MD and pattern standard deviation (PSD) were significantly worse in subjects with DM1 compared with controls (p = 0.010 and p = 0.013 respectively). Among structural parameters, average peripapillary RNFL thickness was reduced in DM1 subjects (p = 0.006). Matrix MD and HFA MD and PSD, and average peripapillary and superior RNFL, were significantly reduced in subjects with DM1 with HbA1c ⩾7% compared with controls. Conclusions: Functional and structural retinal testing by Humphrey Matrix and GDx VCC could be useful for the identification of early retinal impairment in people with DM1 with no sign of retinal vasculopathy.

Adaptive optics imaging of parafoveal cones in type 1 diabetes.

Purpose: To evaluate the parafoveal cone density in patients with Type 1 diabetes mellitus (DM1). Methods: Adaptive optics retinal images of the photoreceptor mosaic were acquired from 11 DM1 patients (study group) and 11 age-matched healthy subjects (control group). Cone density was analyzed, along the horizontal and vertical meridian, at 230-µm, 350-µm, and 460-µm eccentricity from the fovea. Central retinal thickness was measured using a Spectralis spectral-domain optical coherence tomography. A multiple regression model was performed to determine the relationships between the explanatory variables (age, glycohemoglobin level, presence of diabetic retinopathy, duration of diabetes, and central retinal thickness) and cone density. Results: Patients had a diagnosis of DM1 in the past 9 years to 21 years. Of these, five patients had a diagnosis of no diabetic retinopathy and six had mild nonproliferative diabetic retinopathy. On average, cone density was 10% lower in the study than in the control group at each retinal eccentricity along the horizontal and vertical meridians (analysis of variance, P < 0.001). The central retinal thickness was thicker in DM1 eyes than in the control eyes (278 ± 20 µm and 260 ± 13 µm; P < 0.05). The model explained 61% (P < 0.01) of the variance of cone density in the population, with the variables representing an abnormal glucose metabolism, that is, a higher glycohemoglobin level, the presence of diabetic retinopathy, and a chronic diabetes, having the highest influence on cone density decline. Conclusion: A subtle decrease of parafoveal cone density was found in DM1 patients in comparison with age-matched control subjects via high-resolution adaptive optics retinal imaging. The cone density decline was moderately associated with a disturbance in the glucose metabolism.

Reproducibility of Macular Thickness Measurements Using Cirrus SD-OCT in Neovascular Age-Related Macular Degeneration

PURPOSE To assess the test-retest variability of central and sectorial macular thickness measurements obtained by Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA) in neovascular age-related macular degeneration (nAMD). METHODS Macular thickness measurements of nine standard ETDRS subfields were obtained and analyzed. The repeatability of macular thickness measurements by Cirrus HD-OCT was assessed by examining the intrasession within subject standard deviation (Sw), coefficient of repeatability (CR), and coefficient of variation (CV), before and after eyes with retinal segmentation errors were excluded. RESULTS Forty-nine nAMD eyes of 49 consecutive patients were included in the study. The CR for the central macular subfield was 42.4 microm (10.5%) and ranged from 12.1 microm (3.7%) for the outer nasal to 41.8 microm (11.4%) for the inner nasal subfields. In a secondary analysis, eyes affected by erroneous detection of inner and outer retinal boundaries (6/49, 12.24%) were excluded. The revised coefficient of repeatability for the central macular subfield was 26.1 microm (8.1%) and ranged from 10.3 microm (3.8%) for the outer superior to 30.2 microm (8.3%) for the inner nasal subfields. CONCLUSIONS Overall, the test-retest variability of Cirrus HD-OCT is good for the central and sectorial macular subfields, with a low incidence of scan artifacts.

Retinal functional changes measured by microperimetry in neovascular age-related macular degeneration patients treated with ranibizumab.

Purpose: To assess functional and structural retinal changes in patients with neovascular age-related macular degeneration treated with intravitreal ranibizumab 0.5 mg. Methods: Eighteen patients with neovascular age-related macular degeneration have been evaluated in this retrospective 24-week follow-up study. All patients were treated with three injections of ranibizumab 0.5 mg, 1 month apart and retreated according to predefined criteria. At baseline, all patients were subjected to visual acuity measurement, fluorescein angiography, microperimetry, and optical coherence tomography stratus. Visual acuity, microperimetry, and optical coherence tomography evaluations were repeated 28 ± 2 days after each injection. Results: Mean retinal sensitivity significantly improved from 3.89 ± 3.0 dB at baseline to 6.61 ± 3.4 dB at 24 weeks (P = 0.044). Mean visual acuity significantly improved from 48.67 ± 8.58 to 60.72 ± 16.09 (P = 0.026); visual acuity improved in 44.4% of patients ≥15 letters (24.5 ± 8.0 letters), and in 38.9% of patients improved <15 letters (6.14 ± 3.7 letters); 16.7% of patients lost <15 letters (7.3 ± 2.1 letters). An improvement of fixation stability from baseline was observed in 33.3% of patients. Central macular thickness significantly decreased from 310.5 ± 85.7 &mgr;m to 217.3 ± 46.8 &mgr;m at 24 weeks (P < 0.001). Conclusions: Although visual acuity and retinal thickness changes seemed to be almost maximum at 4 weeks after intravitreal ranibizumab 0.5 mg, retinal sensitivity as measured by microperimetry showed a trend of progressive improvement till 24 weeks suggesting that microperimetry may give additional information about macular function not given by visual acuity alone.

Demographic and clinical factors associated with development of brimonidine tartrate 0.2%-induced ocular allergy.

Purpose:To identify demographic and clinical characteristics associated with the development of brimonidine tartrate 0.2%-induced ocular allergy. Patients and Methods:In this retrospective study, 133 patients affected by primary open-angle, pigmentary, narrow angle, or pseudo-exfoliative glaucoma and treated with brimonidine tartrate 0.2% were divided into two groups: allergic and non allergic to brimonidine tartrate 0.2%. The distribution of demographic (age and sex), local (history of allergic conjunctivitis, previous eye-drop ocular allergy, use of other concurrent topical medications, amount of topical medications previously used, use of contact lenses, and tear film production), and systemic (history of systemic allergies and use of systemic drugs) factors was evaluated by comparing the brimonidine tartrate 0.2% allergic and the non-allergic groups. Results:In this study, 13.5% of patients (18 of 133) developed brimonidine ocular allergy generally within two weeks from the beginning of treatment (mean time 14.8 ± 17.9 days). The brimonidine tartrate 0.2% allergic group showed a significantly higher frequency of history of ocular allergy to eye-drops (P = 0.048) and to topical beta-blockers (P = 0.019) when compared with the brimonidine tartrate 0.2% non-allergic group. Moreover, the allergic group showed a decreased tear film production (P = 0.044). Conclusion:This study showed that history of eye-drop allergies and reduction of tear film production were more frequently associated with the development of brimonidine tartrate 0.2%-induced ocular allergy.

Microperimetric retinal changes in myopic choroidal neovascularization treated with intravitreal ranibizumab.

Purpose: The purpose of this study was to report functional and morphologic retinal changes after intravitreal injections of 0.5 mg ranibizumab in patients with myopic neovascular membrane (choroidal neovascularization). Methods: This is a case review of 11 consecutive patients with myopic choroidal neovascularization who received intravitreal injections of ranibizumab at monthly intervals. Serial changes in best-corrected visual acuity, optical coherence tomography, fluorescein angiography, and microperimetry (Nidek MP1, Nidek, Padova, Italy) are presented. Results: Mean baseline best-corrected visual acuity was 59.82 ± 17.50 Early Treatment Diabetic Retinopathy Study letters. After a follow-up of 36 weeks, mean visual acuity improved to 66.72 ± 17.3 with a mean change of 6.91 letters. Mean baseline retinal sensitivity was 6.02 ± 1.9 dB. After 36 weeks, mean sensitivity improved to 8.3 ± 2.4 dB with a mean change of 2.3 dB. The fixation stability improved from 45.5% to 72.7%. All patients also had complete resolution of subretinal fluid, mean optical coherence tomography central retinal thickness was reduced from 244.64 ± 39.3 &mgr;m to 191.36 ± 27.3 &mgr;m at 36 weeks, and fluorescein angiography at 36 weeks showed absence of leakage in all patients. Conclusion: Intravitreal ranibizumab injections seemed to positively influence retinal functional status in patients with myopic choroidal neovascularization.

Reliability of the IOLMaster in axial length evaluation in silicone oil-filled eyes

PurposeTo assess the reliability of IOLMaster in axial length (AL) measurement in phakic silicone oil-filled vspseudophakic saline-filled eyes.MethodsTen eyes of 10 patients, vitrectomized with silicone oil tamponade and scleral buckled with significant lens opacity were enrolled. Optical biometry with IOLMaster (Carl Zeiss Meditec AG, Germany) was performed 1 day before and 1 week after silicone oil removal and phacoemulsification with artificial intraocular lens (IOL) implantation in order to assess changes in AL measurements.ResultsMean AL was 26.16±1.23 mm (range 24.64–28.8 mm) and 26.27±1.46 mm (range 25.26–29.6 mm), respectively, the day before and 1 week after silicone oil removal and cataract surgery, and the difference was not statistically significant (P=0.2).ConclusionsPresence vsabsence of silicone oil tamponade as well as phakic vspseudophaphakic status in buckled and vitrectomized eyes did not influence the AL measurement by means of no-contact optical biometry, suggesting that such eyes might be candidate for silicone oil removal and cataract surgery at one time.