Maria Vittoria Cicinelli

Vessel density analysis in patients with retinitis pigmentosa by means of optical coherence tomography angiography

Aims To describe the vascular abnormalities in patients affected by retinitis pigmentosa (RP) by means of optical coherence tomography angiography (OCT-A). Methods Cross-sectional case series; patients with RP presenting at the Medical Retina Service of the Department of Ophthalmology, University Vita-Salute San Raffaele in Milan were recruited. Inclusion criteria were: diagnosis of RP, clear ocular media, adequate pupillary dilation, and stable fixation. Patients underwent best-corrected visual acuity (BCVA), biomicroscopy, short-wavelength fundus autofluorescence (SW-FAF), and 3×3 Swept Source OCT-A. 30 healthy subjects were chosen as controls. The main outcome was identification of abnormalities in density of the superficial capillary plexus (SCP) and deep capillary plexus (DCP), along with abnormalities of the choriocapillaris (CC). Results 16 patients (32 eyes) were recruited (6 females, 37.4%). Mean age was 53±18 years; mean BCVA was 0.5±0.3 LogMAR. Vessel density analysis disclosed a statistical significant difference in the SCP (29.5±6.8 vs 34.1±4.3; p=0.009) and in the DCP (28.7±7.5 vs 35.5±5.7; p=0.001) between the patients and the controls. No difference was found at the level of the CC (51±4.4 vs 51.3±2.2; p=0.716). RP patients showed a bigger foveal avascular zone at the DCP level compared to controls (p<0.001). Conclusions This study showed that most of the vascular impairment in patients affected by RP localised in the DCP, with relative sparing of the SCP and CC. DCP alterations were more pronounced outside the hyper-autofluorescent ring on SW-FAF. Vascular impairment may preclude good treatment outcomes in RP patients.

Vascular abnormalities in patients with Stargardt disease assessed with optical coherence tomography angiography

Aims To describe the vascular abnormalities in patients affected by Stargardt disease (STGD1) by means of optical coherence tomography angiography (OCT-A). Methods Cross-sectional case series, with the following inclusion criteria: diagnosis of STGD1, clear ocular media, and stable fixation. Patients underwent best-corrected visual acuity (BCVA), biomicroscopy, applanation tonometry, short-wavelength fundus autofluorescence (SW-FAF) (HRA Heidelberg, Germany), 3×3 Swept Source OCT-A (Topcon Corporation, Japan). Foveal avascular zone (FAZ) area was manually outlined and removed from the vessel density analysis (ImageJ). Main outcome was vessel density assessment in the superficial capillary plexus (SCP), in the deep capillary plexus (DCP), and in the choriocapillaris (CC) of patients with STGD1. Results Nineteen patients (36 eyes) were recruited for the study (10 females, 52.6%). Mean age was 33±5.7 years and mean BCVA was 0.6±0.3 logarithm of the minimum angle of resolution. Thirty-six healthy age-matched subjects (one eye for each patient) acted as a control group. Qualitative analysis of OCT-A revealed areas of reduced vascular density in superficial and DCPs. CC showed focal defects partially corresponding to the flecks on SW-FAF imaging. Quantitative analysis of OCT-A disclosed a statistically significant difference in the density of the SCP (0.302±0.062 vs 0.365±0.042; p=0.0002) and the DCP (0.303±0.081 vs 0.399±0.045; p<0.001) compared with controls. To analyse CC, patients with STGD1 were divided into two groups, according to the presence of chorioretinal atrophy. Patients with atrophy showed significantly lower CC density compared with controls (p=0.0003) and patients without atrophy (p=0.001). Patients with STGD1 showed a larger FAZ at the SCP level compared with controls (p=0.012). Conclusions Vascular impairment in patients affected by STGD1 is concentrated in superficial and the deep retinal plexuses. Patients with atrophic changes have a greater reduction in CC density compared with controls (‘dark atrophy’). Morphological vascular evaluation may become an important step for predicting STGD1 treatment outcomes.

Choroid morphometric analysis in non-neovascular age-related macular degeneration by means of optical coherence tomography angiography

Aims To describe the vascular changes in patients affected by non-neovascular age-related macular degeneration (AMD), featuring reticular pseudodrusen (RPD), drusen, or both RPD and drusen by means of optical coherence tomography angiography (OCT-A). Methods Cross-sectional observational case series. Patients with non-neovascular AMD presenting at the Medical Retina Service of the Department of Ophthalmology, University Vita-Salute San Raffaele in Milan were recruited. Patients underwent best-corrected visual acuity, biomicroscopy, infrared reflectance, short-wavelength fundus autofluorescence and OCT-A (AngioPlex, CIRRUS HD-OCT 5000, Carl Zeiss Meditech, Dublin, USA). Main outcome was quantification of vessel density, stromal tissue, and vascular/stromal (V/S) ratio at the choriocapillaris (CC), the Sattler and Hallers and the whole choroid layers among different groups of patients with non-neovascular AMD by means of binarised OCT-A scans. Results 45 eyes of 34 patients were enrolled (15 eyes of 11 patients with RPD, group 1; 15 eyes of 11 patients with drusen, group 2; 15 eyes of 12 patients with mixed phenotype, group 3). The CC, the Sattler and Hallers and the whole choroid vessel density were reduced in all groups of patients (p=0.023, p=0.007 and p=0.011 in group 1, group 2 and group 3 for the CC; p=0.021, p=0.037 and p=0.043 in group 1, group 2 and group 3 for the Sattler and Hallers density; p=0.016, p=0.002 and p<0.001 in group 1, group 2 and group 3 for the choroidal density), with significantly lower V/S ratios compared with healthy controls. Conclusions Patients with non-neovascular AMD show significant choroidal vascular depletion and fibrotic replacement, suggesting a possible role in the pathogenesis and progression of the disease.

CLINICAL SPECTRUM OF MACULAR-FOVEAL CAPILLARIES EVALUATED WITH OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

Purpose: To describe macular-foveal capillaries (MFC) by means of optical coherence tomography angiography and to identify the clinical spectrum of this angiographic feature. Methods: Patients with MFC presenting at the Medical Retina & Imaging Unit of the Department of Ophthalmology, University Vita-Salute San Raffaele in Milan were recruited. Patients underwent a complete ophthalmologic examination that included slit-lamp examination, fundus examination, measurement of best-corrected visual acuity, fundus autofluorescence, and spectral-domain optical coherence tomography (Spectralis HRA + OCT; Heidelberg Engineering, Heidelberg, Germany). Fluorescein angiography was performed in selected cases. Optical coherence tomography angiography was performed through Zeiss prototype (AngioPlex, CIRRUS HD-OCT models 5000; Carl Zeiss Meditec, Inc, Dublin, OH). Results: Twelve eyes of 10 consecutive white patients (5 men and 5 women; 50%) presenting MFC were included. Mean age was 66.2 ± 10.2 years (range, 53–79 years); mean best-corrected visual acuity was 0.1 ± 0.13 logarithm of the minimum angle of resolution (range, 0–0.4 logarithm of the minimum angle of resolution, corresponding to 20/20 to 20/50). Mean central macular thickness was 348 ± 57.6 &mgr;m. Two patients were affected by macular pucker, two by postsurgical macular edema, two by age-related macular degeneration, one by diabetic retinopathy, one by dome-shaped macula, one presented with chronic serous chorioretinopathy, and one with branch artery occlusion. Six eyes disclosed a complete absence of the foveal avascular zone, whereas the six other cases showed a partial foveal avascularity. No significant difference was found between complete and incomplete MFC with regards to best-corrected visual acuity (P = 0.272) and central macular thickness (P = 0.870). Conclusion: Cases of persistent MFC are heterogeneous in demographic characteristics, fundus appearance, and visual function. However, MFC, presenting either as complete absence of the foveal avascular zone or only partial foveal avascularity, may complicate different retinal abnormalities or represents a coincident finding.

Changes in macular function after ozurdex for retinal vein occlusion.

Purpose To investigate changes in macular function after intravitreal dexamethasone implant (Ozurdex) for macular edema (ME) secondary to retinal vein occlusion (RVO). Methods Nineteen treatment-naive patients with RVO-related ME were treated with intravitreal Ozurdex and followed up to 6 months to evaluate functional outcomes, by means of best-corrected visual acuity, microperimetry, and multifocal electroretinography, and their correlations with morphological parameters by enhanced depth imaging optical coherence tomography. Results Nineteen eyes of 19 patients were included for analysis. At 1 month, mean best-corrected visual acuity, retinal sensitivity, and central macular thickness (CMT) improved from 0.50 ± 0.34 LogMAR, 10.51 ± 4.31 dB, and 762 ± 259 &mgr;m (baseline) to 0.38 ± 0.34 LogMAR (p = 0.043), 12.28 ± 5.06 dB (p = 0.025), and 385 ± 191 &mgr;m (p = 0.001), respectively. At 3 months, improvement of mean retinal sensitivity and CMT was still significant (11.62 ± 5.05 dB [p = 0.047] and 518 ± 251 &mgr;m [p = 0.006]). Multifocal electroretinography measurements also showed (nonsignificant) improvement. No significant changes in choroidal thickness were recorded. Improvements recorded during the first 3 months were no longer significant from month 4. At each time point, we found a negative significant correlation between CMT and retinal sensitivity. Interestingly, 7 eyes did not undergo retreatment of less than 6 months; these eyes showed a significantly better baseline retinal sensitivity than eyes requiring retreatment of less than 6 months (12.27 ± 3.52 dB vs. 9.48 ± 4.53 dB [p = 0.038]). Conclusions In eyes with ME secondary to RVO, intravitreal dexamethasone implant provides functional benefits as soon as 1 month after treatment. In most cases, the optimum retreatment interval is less than 6 months from first intravitreal Ozurdex. Microperimetry is a very useful tool to characterize macular function. Baseline macular sensitivity may predict the need for early (<6 months) retreatment.

Mp1 And Maia Fundus Perimetry In Healthy Subjects And Patients Affected By Retinal Dystrophies

Purpose: To compare retinal sensitivity obtained with MP1 and MAIA microperimeters in patients affected by retinal dystrophies (RD) and in healthy subjects. Methods: Thirty-six patients affected by RD and 25 healthy subjects were considered for the study. All patients and controls underwent a complete ophthalmic examination including fundus-related perimetry, performed by means of two microperimeters, the MP1 (Nidek Technologies) and the MAIA (CenterVue). Main outcome of the study was the comparison of retinal sensitivity. Such comparison was performed converting the MP1 decibel (dB) values to their MAIA equivalent dB values. Results: Mean retinal sensitivity in patients affected by RD was 5.68 ± 6.08 dB (mean ± SD) on MP1 (9.66 ± 10.06 dB converted to their equivalent MAIA values) and 14.66 ± 9.37 dB on MAIA (P < 0.0001). Mean retinal sensitivity in healthy subjects was 18.46 ± 3.10 dB on MP1 (22.44 ± 7.08 dB on their converted equivalent MAIA values) and 28.52 ± 1.12 dB on MAIA (P < 0.0001). Thirty eyes affected by RD (41%) showed retinal areas characterized by sensitivity under 1 dB on MP1, whereas the MAIA examination of the same areas revealed a mean retinal sensitivity of 4.7 dB. Moreover, 28 of these eyes disclosed also areas of absolute scotoma on MP1, but examining the same areas on MAIA, just 13 of these eyes (46%) disclosed an absolute scotoma. In addition, in a subgroup of 6 eyes affected by RD (8%) showing a retinal sensitivity of 20 dB on MP1, the corresponding value on MAIA varied from 26.3 dB to 30.0 dB, with a mean value of 27.8 ± 1.3 dB. Conclusion: The MAIA microperimeter provides a more accurate characterization of functional impairment in RD with respect to the MP1 system, especially in cases with low and high retinal sensitivity. MAIA microperimeter could reveal particularly useful in precisely identifying and monitoring subtle changes in retinal sensitivity, especially in view of the availability of therapies aiming at a functional rescue in patients with RD.

Morpho-functional correlation of fundus autofluorescence in Stargardt disease

Background To correlate patterns in short-wavelength (SW) and near-infrared (NIR) fundus autofluorescence (FAF) with morpho-functional outcomes in eyes affected by Stargardt disease. Methods Fifty-four eyes of 27 patients were prospectively enrolled. All patients underwent a complete ophthalmologic examination including SW-FAF, NIR-FAF, microperimetry and spectral-domain optical coherence tomography (SD-OCT). The main outcome measures were identification of a correlation between NIR-FAF and SW-FAF patterns within the foveal region and best corrected visual acuity (BCVA) values. Secondary outcome measures were correlation of FAF patterns with SD-OCT findings and retinal sensitivity on microperimetry. Results Eyes showing a pattern of foveal hyper-FAF on NIR-FAF had a higher BCVA than eyes with a reduced FAF signal (0.44±0.23 LogMAR vs 1.08±0.19, p<0.001). Similarly, mean sensitivity within 2° of the foveal region was significantly better (6.45±2.39 dB) in eyes with hyper-FAF than in eyes with hypo-FAF (0.23±0.45 dB, p<0.001). Moreover, eyes with hyper-FAF on SW-FAF did not present a significant difference in BCVA (0.73±0.31 vs 0.83±0.43, p=0.335) and mean retinal sensitivity (4.34±3.91 dB vs 2.33±2.96, p=0.07) compared with the subgroup with foveal hypo-FAF. The integrity of both the photoreceptor inner/outer segment junction and the photoreceptor outer segment/retinal pigmented epithelium junction was significantly correlated with a preserved BCVA and a foveal hyper-FAF pattern on NIR-FAF. Conclusions Our data suggest that NIR-FAF patterns correlate with morpho-functional outcomes in eyes affected by Stargardt disease. Longitudinal investigations are warranted to assess more precisely the actual contribution of NIR-FAF in the clinical characterisation of Stargardt disease.

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.

Early response to ranibizumab predictive of functional outcome after dexamethasone for unresponsive diabetic macular oedema

Purpose To analyse the effects of intravitreal dexamethasone implant in patients suffering from diabetic macular oedema (DME) on the basis of their visual and functional response to antivascular endothelial growth factor (VEGF) loading dose, in order to early shift to corticosteroids in poorly responding patients. Design Retrospective monocentric study. Methods Data of patients with diabetes shifted to 0.7 mg dexamethasone implant after three injections of ranibizumab (RNB) and followed-up to 12 months were reviewed. Main outcome was the evaluation of short-term changes after dexamethasone implant injection, stratifying patients on the basis of best-corrected visual acuity (BCVA) and central macular thickness (CMT) after RNB loading dose. Secondary outcome was to investigate clinical gain maintenance at long-term follow-up. Results Overall, 45 eyes of 45 patients (23 males, 51.1%), mean age 69.7±9 years, were included in the analysis. After 3 injections of RNB, 30 eyes (66.7%) had a poor visual response (−4.3±10.7 letters), while 15 eyes (33.3%) disclosed good visual outcome (+13.9±9.2 letters). Patients with poor visual response were associated with limited morphological improvement (p=0.04). After 1 month from dexamethasone, only poor responders showed relevant increase in BCVA (p=0.006) and reduction in CMT (p=0.002), in comparison to good visual response patients, featuring only minor clinical effects (p=0.3). The same trend was maintained up to 12 months, after a mean of 1.9±1.1 dexamethasone administrations. Conclusion Visual and anatomical responses after RNB loading dose are significant predictors of both early term and long-term visual acuity improvement after switching to corticosteroids in patients with DME unresponsive to anti-VEGF.

Optical coherence tomography and pathological myopia: an update of the literature

The purpose of this paper is to give an updated review of the last clinical entities in pathological myopia proposed by means of new generation optical coherence tomography (OCT), including enhanced depth imaging (EDI-OCT) and swept source OCT (SS-OCT). PubMed and Google engine search were carried out using the terms “pathological myopia” associated with “coherence tomography,” “enhanced depth imaging,” and “swept source OCT.” Latest publications up to Jan 2015 about myopia-related complications, including open-angle chronic glaucoma, peripapillary retinal changes, acquired macular diseases, and choroidal neovascularization, have been reviewed. New OCT technologies have led to a greater insight in pathophysiology of high-grade myopia. However, further investigation is needed in order to prevent irreversible visual loss and optic nerve damage.