Lorenzo Iuliano

Retinal nerve fiber layer thickness reproducibility using seven different OCT instruments.

PURPOSE The clinical utility of new optical coherence tomography (OCT) instruments strongly depends on measurements reproducibility. The aim of this study was to assess retinal nerve fiber layer (RNFL) thickness reproducibility using six different spectral-domain OCTs (SD-OCTs) and one time-domain OCT. METHODS RNFL thickness (average and four quadrant) from six SD-OCTs (Spectral OCT/SLO OPKO/OTI, 3D-OCT 2000 Topcon, RS-3000 NIDEK, Cirrus HD-OCT Zeiss, RTVue-100 Optovue, and Spectralis Heidelberg) and one time-domain OCT (Stratus OCT Zeiss) was measured twice in 38 right eyes of 38 randomly chosen healthy volunteers by two masked operators. Inter- and intraoperator reproducibility was evaluated by the intraclass correlation coefficient (ICC), coefficient of variation (CV), and Bland-Altman test analysis. Instrument-to-instrument reproducibility was determined by ANOVA for repeated measures. We also tested how the devices disagree in terms of systemic bias and random error using a structural equation model. RESULTS Mean RNFL average thickness ranged from 90.08 μm to 106.51 μm. Cirrus and Heidelberg showed the thinnest RNFL values in all measurements, Topcon the highest. ICC, CV, and Bland-Altman plots showed variable inter- and intraoperator agreement depending on the instrument. Heidelberg demonstrated the best interoperator (ICC, 0.92; CV, 1.56%) and intraoperator (ICC, 0.94 and 0.95; CV, 1.28% and 1.26%, respectively, for operator A and operator B) agreement for average RNFL thickness. CONCLUSIONS Heidelberg demonstrated the higher agreement in inter- and intraoperator reproducibility, Optovue the worst. In light of our error analysis results, we found that a scale bias among instruments could interfere with a thorough RNFL monitoring, suggesting that best monitoring is obtained with the same operator and the same device.

Impending corneal perforation after collagen cross-linking for herpetic keratitis

Collagen crosslinking (CXL) has been proposed as a treatment for infectious keratitis. Given the insurgence of antibiotic-resistant microorganisms and frequent toxicity of topical medications, CXL may be a potential treatment for corneal infections. However, corneal infection is itself a possible complication of this treatment. We describe a case of severe corneal thinning and melting in a woman who had a CXL procedure as a treatment for herpetic keratitis.

Tear osmolarity in ocular graft-versus-host disease.

Purpose: The aim of this study was to evaluate tear osmolarity in patients with chronic graft-versus-host disease (cGVHD) with ocular involvement. Methods: In this observational cross-sectional study of 56 patients with ocular cGVHD referred to the tertiary-care Ocular Immunology and Uveitis Service at the San Raffaele Scientific Institute, Milan, from May 2010 to November 2013, we evaluated the following clinical parameters: Ocular Surface Disease Index (OSDI) symptoms questionnaire, tear osmolarity, Schirmer test, tear film break-up time (TBUT), corneal and conjunctival staining. Results: All patients developed systemic GVHD after undergoing allogeneic hematologic stem cell transplantation. Mean osmolarity was 314.0 ± 22.1 mOsm/L, mean OSDI score was 26.4 ± 21.2, mean TBUT was 6.50 ± 4.75 seconds, and mean Schirmer test value was 3.8 ± 3.3 mm. Tear osmolarity significantly inversely correlated with TBUT (r2 = 0.681; P < 0.001). Statistically significant inverse correlation was present with the Schirmer test (r2 = 0.203; P < 0.001), and positive correlation with the OSDI score (r2 = 0.188; P < 0.001), but both with low correlation strength. Osmolarity was statistically different in the subgroups according to the Oxford corneal staining scale (P = 0.0006) and to the van Bijsterveld conjunctival staining score (P = 0.006). Conclusions: Tear osmolarity increased in patients with ocular cGVHD, significantly correlated with TBUT and, to a lesser extent, with the Schirmer test value and OSDI. These results emphasize the role of aqueous-deficient and evaporative dry eye disease in patients with cGVHD after undergoing allogeneic hematologic stem cell transplantation. Tear osmolarity may be considered a useful test in diagnostic assessment of dry eye disease associated with cGVHD.

A novel spectral-domain optical coherence tomography model to estimate changes in vitreomacular traction syndrome

PurposeTo analyze the course of eyes with vitreomacular traction (VMT), and to find by optical coherence tomography (OCT) possible correlations between vitreomacular interface area changes and the chance of spontaneous VMT resolution.MethodsRetrospective analysis of all consecutive patients presenting with VMT over a 24-month period. We introduced a novel OCT evaluation model to assess the vitreomacular interface area. Central foveal thickness (CFT) and best-corrected visual acuity (BCVA) were also analyzed throughout follow-up.ResultsTwenty-six eyes of 18 symptomatic patients were followed for 12.9 ± 4.8 months. Eyes were subdivided into groups according to their clinical course. Six eyes (23%) had a spontaneous resolution of the VMT (group A), and the interface area before its occurrence (39565 ± 26409 μm2) was smaller than at study entry (99434 ± 38819 μm2; p = 0.03). The interface area did not significantly change throughout follow-up in the group that underwent surgery (group B, 11 eyes) and in the group that remained overall stable (group C, 9 eyes). At baseline, the interface area was smaller in group A compared to groups with non-resolved VMT (mean values of group B and C together) (785095 ± 920721 μm2; p = 0.002). CFT and BCVA did not significantly change in any of the studied groups. Vitreomacular interface area of 101002 μm2 was identified as the threshold value separating the spontaneous VMT resolution group from the group with non-resolved VMT (p < 0.001).ConclusionsThe more the vitreomacular interface area reduced over time, the higher was the chance of spontaneous VMT resolution. An area below 101002 μm2 was the threshold value indicating a higher chance of spontaneous release of VMT.

Vitreomacular traction syndrome: a comparison of treatment with intravitreal plasmin enzyme vs spontaneous vitreous separation without treatment

PurposeTo evaluate the effects of intravitreal autologous plasmin enzyme (APE) in patients with focal vitreomacular traction (VMT).MethodsAPE was obtained by incubation of patient-derived purified plasminogen with streptokinase, and intravitreally injected 5–12 days later. Twenty-four hours after injection, in case of incomplete VMT release, a pars plana vitrectomy was performed. The hyaloid internal limiting membrane adherence and removal of the posterior hyaloid were intraoperatively evaluated.ResultsThirteen patients were recruited. During preparation of APE, five patients had spontaneous release of VMT. Eight patients received APE injection (2 IU). In five patients, spontaneous resolution of VMT occurred before APE administration. Twenty-four hours after injection, persistence of VMT was detected in all the eight treated patients. Best-corrected visual acuity was 0.51±0.37 LogMAR at baseline, improving to 0.23±0.14 LogMAR at 6 months (P=0.002). Foveal thickness was 464±180 μm at baseline, reducing to 246±59 μm at 6 months (P<0.001). Hyaloid was intraoperatively judged ‘partially detached’ in seven cases and ‘totally detached’ in one case. Hyaloid peeling was evaluated ‘easy’ in six eyes and ‘very easy’ in two eyes.ConclusionsIn the current study, there was a large percentage of spontaneous resolution of VMT before an APE administration. A single intravitreal APE injection seems insufficient to induce a complete posterior vitreous detachment in these patients.

Fundus Autofluorescence Changes After Ranibizumab Treatment for Subfoveal Choroidal Neovascularization Secondary to Pathologic Myopia

PURPOSE To describe fundus autofluorescence (FAF) patterns of myopic choroidal neovascularization (CNV) treated with intravitreal ranibizumab and their correlation with visual acuity. DESIGN Prospective interventional case series. METHODS Twenty-seven eyes (27 patients) affected by myopic CNV were enrolled from January 2011 to January 2013. All patients underwent a complete ophthalmologic examination, including best-corrected visual acuity (BCVA) determination and fundus autofluorescence (FAF). The patients underwent ranibizumab injections following a pro re nata treatment regimen. The main outcome measure was the identification of the FAF patterns of myopic CNV over a 12-month follow-up. The secondary outcome was the correlation of the FAF patterns with the BCVA. RESULTS At baseline 17 eyes (63%) showed a hyperautofluorescent pattern and 10 eyes (37%) a patchy pattern. BCVA changed from 0.48 ± 0.23 (logMAR) to 0.30 ± 0.32 at the 12-month examination (P = .027) in the hyper-FAF subgroup. In the subgroup showing the patchy pattern, the BCVA declined slightly from 0.51 ± 0.27 to 0.56 ± 0.37 (P = .53). The 14 eyes preserving the hyper-FAF pattern during the follow-up had a final BCVA of 0.20 ± 0.17, whereas the 9 eyes maintaining the patchy pattern showed a final BCVA of 0.60 ± 0.37 (P = .002). The atrophic area of the retinal pigment epithelium assessed on the basis of FAF increased from 1.27 ± 2.80 mm(2) to 1.83 ± 3.74 mm(2) at the 12-month examination (P = .016). The mean atrophic area increased by 0.37 mm(2) in the hyper-FAF subgroup and by 0.90 mm(2) in the patchy FAF subgroup. CONCLUSIONS Two main patterns were identified on FAF in myopic CNV and were related to the prognostic evolution, the hyperautofluorescent CNV being associated with a greater visual gain and fewer atrophic changes over a 12-month follow-up.

Retinal neurovascular changes appear earlier in type 2 diabetic patients.

Purpose To investigate the early neurodegenerative changes of inner retina and choroid in type 1 and type 2 diabetic patients without retinopathy and with early-stage retinopathy. Methods In this observational cross-sectional study, 90 right eyes of 90 naive type 1 and 2 diabetic patients without diabetic retinopathy (DR) and with mild to moderate nonproliferative DR (NPDR) were analyzed. Forty healthy eyes were included as controls. We used spectral-domain optical coherence tomography to evaluate the ganglion cell complex (GCC) thickness, the retinal nerve fiber layer (RNFL) thickness, the choroid thickness, and the central foveal thickness (CFT) of patients and controls. Results Average GCC thickness turned out to be thinner in type 2 diabetic patients with no DR and with NPDR compared to controls (p = 0.046 and p = 0.041, respectively). The RNFL thickness and CFT were similar among the studied groups and compared to controls (p = 0.78 and p = 0.104, respectively). Average choroid thicknesses (both in the subfoveal area and in a 1-mm radius circular area) were significantly thinner in type 2 diabetic patients with no DR and NPDR, compared to DMT1 groups and controls (both p<0.0001). The GCC and choroid thickness changes were not correlated in any of the investigational groups. Conclusions Type 2 diabetic patients without retinopathy and with early-stage retinopathy have inferior thickness values of GCC and choroid compared to controls. Insulin resistance might be a possible adjunctive pathogenetic aspect of neurodegeneration.

Central Corneal Thickness Reproducibility among Ten Different Instruments

Purpose To assess agreement between one ultrasonic (US) and nine optical instruments for the measurement of central corneal thickness (CCT), and to evaluate intra- and inter-operator reproducibility. Methods In this observational cross-sectional study, two masked operators measured CCT thickness twice in 28 healthy eyes. We used seven spectral-domain optical coherence tomography (SD-OCT) devices, one time-domain OCT, one Scheimpflug camera, and one US-based instrument. Inter- and intra-operator reproducibility was evaluated by intraclass correlation coefficient (ICC), coefficient of variation (CV), and Bland-Altman test analysis. Instrument-to-instrument reproducibility was determined by ANOVA for repeated measurements. We also tested how the devices disagreed regarding systemic bias and random error using a structural equation model. Results Mean CCT of all instruments ranged from 536 ± 42 &mgr;m to 577 ± 40 &mgr;m. An instrument-to-instrument correlation test showed high values among the 10 investigated devices (correlation coefficient range 0.852–0.995; p values <0.0001 in all cases). The highest correlation coefficient values were registered between 3D OCT-2000 Topcon—Spectral OCT/SLO Opko (0.995) and Cirrus HD-OCT Zeiss—RS-3000 Nidek (0.995), whereas the lowest were seen between SS-1000 CASIA and Spectral OCT/SLO Opko (0.852). ICC and CV showed excellent inter- and intra-operator reproducibility for all optic-based devices, except for the US-based device. Bland-Altman analysis demonstrated low mean biases between operators. Conclusions Despite highlighting good intra- and inter-operator reproducibility, we found that a scale bias between instruments might interfere with thorough CCT monitoring. We suggest that optimal monitoring is achieved with the same operator and the same device.

Tear film osmolarity in ocular mucous membrane pemphigoid.

Purpose: The aim of this study was to evaluate tear film osmolarity in patients with ocular mucous membrane pemphigoid (MMP). Methods: This observational cross-sectional study included 40 patients with biopsy-proven ocular MMP at Foster stage III referred to the tertiary-care Ocular Immunology and Uveitis Service at the San Raffaele Scientific Institute in Milan from June 2010 to August 2013. We evaluated the following clinical parameters: tear film osmolarity, ocular surface disease symptoms (OSDI) questionnaire, Schirmer test, tear film break-up time (TFBUT), and corneal and conjunctival staining. Results: Forty patients (27 women and 13 men) were enrolled. All patients were undergoing systemic immunosuppressive therapy: 19 patients (47.5%) were on methotrexate, 9 (22.5%) were on mycophenolate mofetil, 9 (22.5%) were on low-dose corticosteroids, and 3 (7.5%) were on azathioprine. The mean osmolarity was 322.90 ± 33.39 mOsm/L, the mean OSDI score was 73.2 ± 17.9, the mean TFBUT was 6.60 ± 3.13 seconds, and the mean Schirmer test value was 4.07 ± 3.58 seconds. Tear film osmolarity significantly correlated with the TFBUT (r2 = 0.80; P < 0.0001), whereas no clinical correlation was found with the Schirmer test value (r2 = 0.01; P = 0.40) or with the OSDI score (r2 = 0.02; P = 0.29). Osmolarity did not turn out to be statistically different in the subgroups according to the Oxford corneal staining scale (P = 0.71) and to the Van Bijsterveld conjunctival staining score (P = 0.31). Conclusions: Tear osmolarity increased in patients with ocular MMP and correlated with the TFBUT. This result emphasizes the role of evaporative dry-eye condition in patients with ocular MMP. Tear osmolarity may be considered as a useful test in the diagnostic assessment of dry eye associated with MMP and for targeting therapeutic decisions.

Review and Perspectives on Pharmacological Vitreolysis

The vitreous is involved in multiple diseases when an incomplete posterior vitreous detachment (PVD) occurs. An incomplete PVD can lead to several pathological conditions. Such visually threatening conditions are traditionally of exclusive surgical interest. In contrast, pharmacological vitreolysis is the effort to reduce or eliminate the pathogenetic role of the vitreous solely by means of drug delivery. Here we aim to review and summarize the evidence available to date about this challenging new approach.