Barbara Boccassini

In vivo detection of monosomy 3 in eyes with medium-sized uveal melanoma using transscleral fine needle aspiration biopsy.

Purpose Cytogenetic prognostication of choroidal melanoma, particularly monosomy 3 detections, is limited to enucleated eyes or resected tumors. The authors developed an in vivo technique to detect monosomy 3 using transscleral fine needle aspiration biopsy (FNAB). Methods Eight eyes with medium-sized choroidal melanoma were included in this prospective study. A 25-gauge transscleral FNAB was performed during surgical procedure for brachytherapy, just before applying the radioactive plaque over the tumor base. Sampled material underwent fluorescence in situ hybridization (FISH) with centromeric probes for chromosome 3. Follow-up was >12 months. Results Transscleral FNAB yielded sufficient material in 7 of 8 eyes (87.5 %). Five of seven eyes had monosomy 3. No early or late complications were detected. Conclusions This study demonstrates that medium choroidal melanomas may be safely sampled by intraoperative transscleral FNAB to detect monosomy 3 in vivo.

Diabetic Macular Edema: Fundus Autofluorescence and Functional Correlations

PURPOSE Diabetic macular edema (DME) shows variable clinical characteristics with unpredictable results to local treatment, probably reflecting different phenotypes. The purpose of this study was to evaluate the role of structural and functional macular imaging in the characterization of DME patterns. METHODS One hundred fifty-one eyes of 92 diabetic patients with untreated clinically significant macular edema (CSME) underwent best corrected visual acuity (BCVA) determination (logMAR), slit lamp biomicroscopy; fluorescein angiography; optical coherence tomography (OCT; mean central retinal thickness [CRT], volume, and DME pattern); fundus autofluorescence (FAF; absent or increased [i]FAF, single or multiple spots; iFAF area quantification); and microperimetry. Linear correlation, data agreement and three-way analysis of covariance were used for statistics. RESULTS Thirty-five (23.2%) eyes had normal FAF; and 116 eyes had iFAF: 48 (31.8%) single-spot iFAF, 68 (45%) multiple-spot iFAF. Retinal sensitivity in areas with iFAF was 11.5±5.3 dB (vs. 15.1±3.9 dB in normal areas, P<0.005). Retinal sensitivity of the central field was 15.1±3.9 dB in normal FAF, 12.4±4.8 dB in single-spot iFAF and 11.4±4.9 dB in multiple-spot iFAF (P<0.05). OCT CRT and volume were not significantly different between the FAF groups. OCT volume correlated to OCT CRT (r=0.68), retinal sensitivity in iFAF (r=-0.50) and BCVA (r=0.42). Cystoid OCT pattern and FA edema patterns correlated with iFAF presence (P<0.0001). CONCLUSIONS In CSME, FAF correlates better with OCT patterns and central field microperimetry rather than with visual acuity. FAF is a rapid, noninvasive technique that may give new insight into the evaluation of DME. The validity of FAF in the follow-up and treatment outcomes in DME remain to be assessed.

The Pathogenesis of Retinal Damage in Blunt Eye Trauma: Finite Element Modeling

PURPOSE To test the hypothesis that blunt trauma shockwave propagation may cause macular and peripheral retinal lesions, regardless of the presence of vitreous. The study was prompted by the observation of macular hole after an inadvertent BB shot in a previously vitrectomized eye. METHODS The computational model was generated from generic eye geometry. Numeric simulations were performed with explicit finite element code. Simple constitutive modeling for soft tissues was used, and model parameters were calibrated on available experimental data by means of a reverse-engineering approach. Pressure, strain, and strain rates were calculated in vitreous- and aqueous-filled eyes. The paired t-test was used for statistical analysis with a 0.05 significance level. RESULTS Pressure at the retinal surface ranged between -1 and +1.8 MPa at the macula. Vitreous-filled eyes showed significantly lower pressures at the macula during the compression phase (P < 0.0001) and at the vitreous base during the rebound phase (P = 0.04). Multiaxial strain reached 20% and 25% at the macula and vitreous base, whereas the strain rate reached 40,000 and 50,000 seconds(-1), respectively. Both strain and strain rates at the macula, vitreous base, and equator reached lower values in the vitreous- compared with the aqueous-filled eyes (P < 0.001). Calculated pressures, strain, and strain rate levels were several orders of magnitude higher than the retina tensile strength and load-carrying capability reported in the literature. CONCLUSIONS Vitreous traction may not be responsible for blunt trauma-associated retinal lesions and can actually damp shockwaves significantly. Negative pressures associated with multiaxial strain and high strain rates can tear and detach the retina. Differential retinal elasticity may explain the higher tendency toward tearing the macula and vitreous base.

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.

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.

Primary blast injury to the eye and orbit: finite element modeling

PURPOSE Primary blast injury (PBI) mostly affects air-filled organs, although it is sporadically reported in fluid-filled organs, including the eye. The purpose of the present paper is to explain orbit blast injury mechanisms through finite element modeling (FEM). METHODS FEM meshes of the eye, orbit, and skull were generated. Pressure, strain, and strain rates were calculated at the cornea, vitreous base, equator, macula, and orbit apex for pressures known to cause tympanic rupture, lung damage, and 50% chance of mortality. RESULTS Pressures within the orbit ranged between +0.25 and -1.4 MegaPascal (MPa) for tympanic rupture, +3 and -1 MPa for lung damage, and +20 and -6 MPa for 50% mortality. Higher trinitrotoluene (TNT) quantity and closer explosion caused significantly higher pressures, and the impact angle significantly influenced pressure at all locations. Pressure waves reflected and amplified to create steady waves resonating within the orbit. Strain reached 20% along multiple axes, and strain rates exceeded 30,000 s(-1) at all locations even for the smallest amount of TNT. CONCLUSIONS The orbits pyramidlike shape with bony walls and the mechanical impedance mismatch between fluidlike content and anterior air-tissue interface determine pressure wave reflection and amplification. The resulting steady wave resonates within the orbit and can explain both macular holes and optic nerve damage after ocular PBI.

Foveal Microstructure and Functional Parameters in Lamellar Macular Hole

PURPOSE To evaluate the morphologic features of the photoreceptor layer (by spectral-domain optical coherence tomography) and functional parameters in patients with a lamellar macular hole. DESIGN Prospective, multicenter, observational case series. METHODS Fifty-four patients with lamellar macular hole were enrolled in the study. All patients underwent a complete ophthalmologic examination, including best-corrected visual acuity (BCVA) testing, MP1 microperimetry, and spectral-domain optical coherence tomography. For each patient, 2 experienced masked observers evaluated the integrity of photoreceptor inner segment/outer segment (IS/OS) junction and external limiting membrane (ELM) line. RESULTS Spectral-domain optical coherence tomography analysis showed complete integrity of the IS/OS junction and ELM line in 40 eyes (group A), partial or complete disruption of the IS/OS junction with an intact ELM line in 8 eyes (group B), and an alteration of both IS/OS junction and ELM line in 6 eyes (group C). Mean BCVA, total retinal sensitivity, and fixation stability were significantly better in groups A and B than in group C (both P < .05, Tukey-Kramer test), whereas there was no significant difference between groups A and B. Mean central retinal sensitivity was significantly different among all 3 groups (all P < .05, Tukey-Kramer test). The grade of integrity of the foveal photoreceptor layer was correlated significantly with mean BCVA (r = -0.57; P < .001), mean central retinal sensitivity (r = 0.52; P < .001), and total retinal sensitivity (r = 0.44; P < .001). CONCLUSIONS In lamellar macular hole, the morphologic features of the foveal photoreceptor layer consistently are correlated with BCVA and central retinal sensitivity. Preservation of the ELM is related to the maintenance of visual acuity.

Long-term outcome of transpupillary thermotherapy as primary treatment of selected choroidal melanoma.

Purpose:  To evaluate prospectively, on a long‐term range, the clinical outcomes of transpupillary thermotherapy (TTT) as primary treatment of selected choroidal melanoma.

Exploring the morphological and functional retinal changes after dexamethasone intravitreal implant (Ozurdex®) in macular edema due to retinal vein occlusion.

Purpose: To explore functional and morphological retinal changes 6 months after dexamethasone intravitreal implant (DEX implant) for the treatment of macular edema due to central or branch retinal vein occlusion (CRVO, BRVO). Procedures: In this prospective interventional case series patients underwent a complete ophthalmological examination at baseline and monthly, including best-corrected visual acuity (BCVA), spectral domain-optical coherence tomography and microperimetry. Fluorescein angiography was performed at baseline and at 4 months. All patients were treated with a DEX implant and retreated according to predefined criteria starting from month 4. Results: Sixteen patients (mean age 66 ± 13 years, 14 CRVO, 2 BRVO) were included. At 6 months mean retinal sensitivity improved from 9.7 ± 4.6 to 13.6 ± 5.4 dB (p < 0.0001) while mean BCVA improved from 52.4 ± 16.2 to 66.1 ± 16.6 (p < 0.0001). Mean central retinal thickness decreased from 708.3 ± 151.01 to 362.7 ± 177.4 μm (p < 0.0001); 56.2% of eyes were retreated at month 4. Conclusions: At 6 months DEX implant led to a significant improvement in retinal sensitivity and visual acuity associated with a reduction of retinal thickness in patients with macular edema due to retinal vein occlusion.