Baseline imaging characteristics and early structural changes in macula on rhegmatogenous retinal detachment.

Animal models have demonstrated that structural changes affect the macula during peripheral rhegmatogenous retinal detachment. This study aimed to assess photoreceptors, retinal and choriocapillaris perfusion in non-macula involving rhegmatogenous retinal detachment by analyzing en-face images from structural OCTA segmented at the ellipsoid zone (EZ) level, calculating (1) "normalized" reflectivity as a surrogate biomarker of photoreceptor damage (2) perfusion density (PD), vessel length density (VLD) and vessel diameter index (VDI) of superficial capillary plexus (SCP) and deep capillary plexus (DCP) (3) perfusion density of choriocapillaris (PDCC). Twenty-one eyes affected by macula-on rhegmatogenous retinal detachment (RRD) were enrolled at the University "G. d'Annunzio", Chieti-Pescara. The fellow unaffected eye was used as control. The mean age at the onset of RRD was 60.09 ± 10.22 (range 34-83). Compared with fellow eyes, we found lower EZ "normalized" reflectivity in macula-on (0.42 ± 0.15 in fellow eyes and 0.31 ± 0.09 in macula on p = 0.004). The affected eye was also characterized by impaired perfusion in SCP (17.26 ± 3.34% in macula on and 20.56 ± 3.62% in the fellow eye p = 0.004) and CC (50.21 ± 6.20% in macula on the eye and 57.43 ± 6.20% in the fellow eye p = 0.004). Macula-on rhegmatogenous retinal detachment has subclinical changes in photoreceptors, SCP, and CC. Future longitudinal studies should evaluate if early changes could impact post-operative macular function.

Choroidal Vascularity Index Fluctuations in Epiretinal Membranes in Vitreoretinal Surgery: Comparison Between Idiopathic and Diabetic Ones.

Purpose: The aim of the study was to analyze choroidal vascularity index (CVI) fluctuations in patients with epiretinal membrane after vitreoretinal surgery, comparing idiopathic and secondary diabetic ones. Methods: Thirty eyes suffering from idiopathic ERMs (I-ERMS; n = 15) and diabetic ERMs (D-ERMS; n = 15) were analyzed in this observational prospective study. Anatomical (central macular thickness) and functional (best-corrected visual acuity) parameters were analyzed preoperatively and at 1 and 3 months after vitrectomy. Perfusion findings regarding CVI and luminal area were also calculated. Results: At 1 month after surgery, the luminal area and CVI significantly decreased in the I-ERMS group, whereas they were increased in the D-ERMS group. At the 3-month follow-up, the CVI tended to return to baseline values in I-ERMS and to reduce in D-ERMS, but without any statistical differences. Conclusions: The significant change in the CVI after surgery seems to imply that the choroidal layer is affected by vitreomacular disease and can become a novel potential biomarker of predictiveness in vitreoretinal surgery. Translational Relevance: The aim of the study was to focus on the early choroidal changes to better understand initial predictive elements of long-term functional postoperative outcomes.

MicroRNA Expression in Subretinal Fluid in Eyes Affected by Rhegmatogenous Retinal Detachment.

Proliferative vitreoretinopathy (PVR) is an abnormal intraocular scarring process that can complicate cases of rhegmatogenous retinal detachment (RRD). Although previous studies have examined the relevance of microRNAs (miRNAs) in ophthalmic diseases, only a few studies have evaluated the expression profiles of microRNAs in subretinal fluid. We hypothesized that the expression profiles of specific miRNAs may change in response to RRD, in the subretinal fluid that is directly in contact with photoreceptors and the retinal pigment epithelium (RPE). We looked for a potential correlation between the expression of specific miRNAs in eyes with RRD and known clinical risk factors of PVR. A total of 24 patients (59 ± 11 years) who underwent scleral buckling procedure were enrolled in this prospective study. Twenty-four undiluted subretinal fluid samples were collected, RNA was isolated and qRT-PCR was performed to analyze the expression of 12 miRNAs. We found the existence of a positive association between the expression of miR-21 (p = 0.017, r = 0.515) and miR-34 (p = 0.030, r = 0.624) and the duration of symptoms related to retinal detachment. Moreover, the expression of miR-146a tended to decrease in patients who developed PVR. Subretinal fluid constitutes an intriguing biological matrix to evaluate the role of miRNAs leading to the development of PVR.

Short-term comparison between navigated subthreshold microsecond pulse laser and oral eplerenone for chronic central serous chorioretinopathy.

To compare the anatomical/functional changes after navigated subthreshold pulse laser (SML) and oral eplerenone therapy for chronic central serous chorioretinopathy (cCSC). A total of 36 eyes of 36 patients suffering from cCSC treated with navigated SML (Navilas® 577s; OD-OS GmbH, near Berlin, Germany) (18 eyes, SML group) and oral eplerenone (18 eyes, eplerenone group) were enrolled in this retrospective study. Main outcome measures during a 3-month follow up period included changes of best corrected visual acuity (BCVA), central macular thickness (CMT), foveal subretinal fluid thickness (FSRFT), and subfoveal choroidal thickness (SFCT). At baseline average duration of symptoms was 6.8 ± 0.6 months in SML group and 6.4 ± 0.9 months in eplerenone group (p = 0.127). Mean BCVA, CMT and FSRFT changed significantly over time (p < 0.001). From baseline to 90 days the BCVA improved from 0.3 ± 0.1 to 0.1 ± 0.1 logMAR in SML group and from 0.3 ± 0. to 0.2 ± 0.1 logMAR in eplerenone group, CMT reduced from 357.1 ± 104.3 to 210.6 ± 46.7 µm and from 428.7 ± 107.7 to 332.5 ± 27.5 µm in SML group and eplerenone group respectively, FSRFT reduced from 144.4 ± 108.2 to 22.6 ± 37.2 µm and from 217.1 ± 105.9 to 54.4 ± 86.2 µm in SML group and eplerenone group. 55.6% of patients in SML group and 66.7% in eplerenone group showed a complete resolution of FSRFT during follow up. The interaction between group and time was statistically significant with greater absolute variation for CMT and FSRFT in SML group compared to eplerenone group (p < 0.001 and p = 0.043). SFCT did not change significantly during follow up (p = 0.083) for both groups. Both navigated SML and oral eplerenone were effective treatments showing recovery of retinal morphology and related visual acuity improvement in cCSC.

MACULAR PIGMENT OPTICAL DENSITY ASSESSED BY HETEROCHROMATIC FLICKER PHOTOMETRY IN EYES AFFECTED BY PRIMARY EPIRETINAL MEMBRANE.

PURPOSE: To compare macular pigment optical density (MPOD) in healthy eyes versus eyes affected by primary epiretinal membrane (ERM) in different stages and to assess the relation between MPOD and optical coherence tomography findings. METHODS: Prospective cross-sectional study of 62 eyes of 62 patients affected by unilateral primary ERM. Contralateral healthy eyes from the same patients were used as a control group. Main outcome measures were MPOD, ERM stage, central foveal thickness (CFT), outer nuclear layer thickness (ONLT), integrity of outer retinal bands, and presence of central bouquet abnormalities. RESULTS: In the study group, mean CFT was 444 ± 75 µm and mean ONLT was 245 ± 40 µm, whereas in the control group, mean CFT was 230 ± 21 µm and mean ONLT was 102 ± 14 µm (P < 0.001). Mean MPOD was 0.86 ± 0.07 in eyes with ERM and 0.48 ± 0.09 in contralateral healthy eyes (P < 0.001). Macular pigment optical density was associated with CFT (P = 0.006) and ONLT (P < 0.001), whereas no significant associations were observed between MPOD and outer retinal bands integrity (P = 0.14) and central bouquet abnormalities (P = 0.08). CONCLUSION: Macular pigment optical density increased in eyes affected by primary ERM proportionally to CFT and, especially, ONLT. Probably, centripetal forces exerted by ERM contraction on the retinal surface lead to a progressive foveal packing of foveal Müller cells.

Early Vascular and Functional Changes after Vitreoretinal Surgery: A Comparison between the Macular Hole and Epiretinal Membrane.

(1) Background: The aim of this observational comparative study was to investigate early retinal vascular and functional changes in patients undergoing vitreoretinal surgery for idiopathic epiretinal membrane (iERM) or macular hole (MH) using a widefield swept-source optical coherence tomography angiography (WSS-OCTA). (2) Methods: Forty one diseased eyes were enrolled in the study. Twenty three eyes with iERM diagnosis (ERM group) underwent 25-gauge vitrectomy with inner limiting membrane (ILM) and MER peeling, while eighteen eyes with MH (MH group) underwent 25-gauge vitrectomy with inverted flap technique. Functional and anatomical/perfusion parameters were evaluated pre- and postoperatively in all eyes by means of WSS-OCTA system, microperimetry (MP3), best corrected visual acuity assessment, central macular thickness (CMT) and MH diameter calculation. For each eye, 12 × 12 mm OCTA volume scans were acquired by a retinal specialist and a semi-automated algorithm was used for a quantitative vessel analysis of the superficial capillary plexus (SCP), deep capillary plexus (DCP) and choriocapillaris (CC). In detail, perfusion density (PD) of the SCP, DCP and CC was evaluated in four circles (one central in the macular area of 5 mm diameter; three midperiphery circles (temporal, superior and inferior) of 3 mm). In addition, the vessel length density (VLD) of the SCP and DCP for the same circles was quantified. (3) Results: In the MH group, PD of the SCP significantly increased in the macular area (p = 0.018) and in the superior ring (p = 0.016); PD of the DCP significantly increased in the macular area (p = 0.015) and in the superior and inferior ring (p = 0.016) 3 months after surgery. In the ERM group, PD of the SCP and DCP significantly increased in the macular area and superior ring, respectively (p = 0.001; p = 0.032), 3 months after surgery. During follow-up there was a significant improvement in terms of functional (Best corrected visual acuity, p = 0.007 and p = 0.029; microperimetry ((MP3) 10°, p = 0.003 and p = 0.004; MP3 2°, p = 0.028 and p = 0.003 in MH group and ERM group respectively) and anatomical parameters (CMT, p = 0.049 in ERM group; hole complete closure in MH group). (4) Conclusions: After vitreoretinal surgery, early retinal vascular and functional changes can be promptly observed and quantified to monitor and potentially predict surgery outcomes. Widefield OCTA devices allow for a detailed microvasculature analysis of retina and choriocapillaris in the macular area and in the periphery, showing a different behaviour of retinal sectors in two distinct vitreoretinal disorders.

Inverted ILM Flap Technique in Idiopathic Full-Thickness Macular Hole Surgery: Functional Outcomes and Their Correlation with Morphologic Findings.

OBJECTIVES: The inverted internal limiting membrane (ILM) flap technique has been shown to increase the success rate in large full-thickness macular holes (FTMHs) and in FTMHs associated with high myopia. The aim of our study was to confirm the efficacy and safety of inverted ILM flap technique in idiopathic FTMHs independent of their dimensions and to assess functional outcomes and their correlation to morphologic findings. METHODS: Sixteen consecutive patients affected by idiopathic FTMH were enrolled in this prospective study. The preoperative mean (±SD) diameter of the FTMH was 422 (±106) µm. All patients underwent vitrectomy and ILM peeling with inverted ILM flap. At 1-, 3-, and 6-month postoperative visits, visual acuity measurement, indirect ophthalmoscopy, and microperimetry were performed, and the foveal contour and the integrity of the ellipsoid zone (EZ) and external limiting membrane (ELM) were investigated using spectral domain optical coherence tomography (SD-OCT). RESULTS: At six months postoperatively, 15 out of 16 (93.75%) patients obtained FTMH closure. The mean best corrected visual acuity (BCVA) improved from 1.1 LogMAR to 0.3 LogMAR, and the mean retinal sensitivity (MS) improved from 7.2 to 23.4 dB. ELM defects were evident in 1 out of 16 (6.25%) eyes, and EZ defects were detected in 2 out of 16 (12,50%) eyes. A statistically significant relationship was observed between BCVA, MS, and EZ reconstitution at each follow-up visit. CONCLUSIONS: Results confirm that the inverted ILM flap technique is a safe and effective option for FTMH treatment and show a strong correlation between higher BCVAs and MSs and EZ reconstitution after surgery.

Early retinal flow changes after vitreoretinal surgery in idiopathic epiretinal membrane using swept source optical coherence tomography angiography.

(1) Background: The aim of this observational cross-sectional work was to investigate early retinal vascular changes in patients undergoing idiopathic epiretinal membrane (iERM) surgery using swept source optical coherence tomography angiography (SS-OCTA); (2) Methods: 24 eyes of 24 patients who underwent vitrectomy with internal limiting membrane (ILM) peeling were evaluated pre- and postoperatively using SS-OCTA system (PLEX Elite 9000, Carl Zeiss Meditec Inc., Dublin, CA, USA). For each eye, five 6x6-mm OCTA volume scans were acquired by two observers independently. The en face images of superficial capillary plexus (SCP) were then exported to imageJ and a semi-automated algorithm was used for subsequent quantitative analysis. Perfusion density (PD), vessel length density (VLD), vessel diameter index (VDI) and vessel tortuosity (VT) of SCP were evaluated in both the parafoveal (2.5 mm diameter) and perifoveal areas (5.5 mm diameter); (3) Results: At OCTA analysis statistically significant differences were found between controls and diseased eyes for all parameters in parafoveal and perifoveal regions (p<0.001; p<0.05) except for perifoveal VLD. During 6-month follow up, both anatomical/perfusion and functional parameters showed a statistically significant improvement if compared to preoperative values. In detail, at one month post vitrectomy, VLD and VT significantly changed in parafoveal region (p=0.043; p=0.045), while PD and VDI showed a trend of increase in both parafoveal and perifoveal region. At 6 months after surgery, PD, VLD and VT of parafoveal region significantly improved (p=0.021, p=0.018, p=0.047 respectively). (4) Conclusions: SS-OCTA provides a quantitative and qualitative analysis of the superficial capillary plexus allowing for early vascular changes assessment after vitrectomy with iERM and ILM peeling.

EPIRETINAL MEMBRANE IN EYES WITH VITREOMACULAR TRACTION.

PURPOSE: To describe the occurrence of epiretinal membrane (ERM) in eyes with vitreomacular traction and to correlate the presence of ERM with retinal structural alterations detected using spectral domain optical coherence tomography. METHODS: In this retrospective observational cross-sectional study, we collected data from 502 eyes (307 patients) with diagnosis of vitreomacular traction. The presence of ERM and retinal lesions (cystoid cavities, neuroepithelial detachment, external limiting membrane, and ellipsoid zone discontinuity) was determined by standardized grading of macular spectral domain optical coherence tomography scans. RESULTS: The occurrence of ERM in eyes with vitreomacular traction was 37.5%. The mean ± SD central foveal thickness was 411 ± 60 µm in eyes with ERM and 380 ± 148 µm in eyes without ERM (P < 0.05). The occurrence of cystoid cavities (38.3% vs. 23.2%, P < 0.05), neuroepithelial detachment (24.5% vs. 9.9%, P < 0.0001), external limiting membrane discontinuity (16.5% vs. 5.1%, P < 0.0001), and ellipsoid zone discontinuity (13.3% vs. 6.7%, P < 0.05) was higher in eyes with ERM. The mean ± SD best-corrected visual acuity was 0.45 ± 0.16 logarithm of the minimum angle of resolution (Snellen equivalent of approximately 20/50) in eyes with ERM and 0.37 ± 0.09 in eyes without ERM (Snellen equivalent of approximately 20/40, P < 0.0001). Symptoms of metamorphopsia were present in 55 of 188 eyes with ERM (29.3%) and 40 of 314 eyes without ERM (12.7%, P < 0.0001). CONCLUSION: This study reported the occurrence of ERM in eyes with vitreomacular traction and demonstrated that ERM is significantly associated with an increased occurrence of other structural changes of the neuroretina and a negative effect on quantity and quality of vision.

Intraoperative optical coherence tomography in the full-thickness macular hole surgery with internal limiting membrane inverted flap placement.

PURPOSE: To describe the helpfulness of using intraoperative optical coherence tomography (OCT) during surgery for full-thickness macular hole (FTMH). OBSERVATIONS: This observational case series identifies three patients with FTMH who were treated with vitrectomy, internal limiting membrane (ILM) peel with inverted ILM flap, which was tucked into the MH, and air with 18% Sulfur Hexafluoride (SF6) gas tamponade. Intraoperative OCT was used to confirm positioning of the ILM flap, even after complete air-fluid exchange. The patients were followed for three months after surgery and all reached a good morphological and functional outcome. CONCLUSIONS: If confirmed by a prospective longitudinal study, the intraoperative OCT might become an important tool in assisting FTMH surgery.

Optical Coherence Tomography Angiography in the Multimodal Imaging Evaluation of Interferon-Associated Retinopathy: A Case Report.

The authors present the case of a 59-year-old woman in treatment with interferon alfa-2b for stage IV melanoma and widespread metastases who presented with interferon-associated retinopathy. An ocular examination revealed multiple retinal cotton-wool spots and hard exudates. Interferon treatment was suspended. The patient was followed up for 5 months following the baseline visit by means of en face optical coherence tomography (OCT), spectral-domain OCT, and OCT angiography. Multimodal imaging was useful in the follow-up of this condition, permitting the characterization of all the lesions hallmarking the interferon-retinopathy and showing that this illness was related to a reduction of the retinal vascular perfusion. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:498-504.].

Subretinal Fluid Levels of Signal-Transduction Proteins and Apoptosis Molecules in Macula-Off Retinal Detachment Undergoing Scleral Buckle Surgery.

Purpose: To evaluate signal transduction and early apoptosis protein levels in subretinal fluid collected during scleral buckling surgery for macula-off rhegmatogenous retinal detachment (RRD). Our aim was to assess both their relation with RRD features and their influence on the posttreatment outcome. Methods: Thirty-three eyes of 33 RRD patients scheduled for scleral buckle surgery were enrolled in the study. Undiluted subretinal fluid samples were collected during surgery and analyzed via magnetic bead-based immunoassay. All patients underwent a complete ophthalmologic evaluation at baseline and at each follow-up visit (months 1, 3, and 6). Moreover, both at baseline and at the postsurgery month 6 visit, the patients were tested by means of spectral-domain optical coherence tomography (SD-OCT) in order to evaluate the average ganglion cell-inner plexiform complex thickness, as well as the photoreceptor inner segment/outer segment junction status. Results: Patients' clinical features (retinal detachment size, detachment duration, and occurrence of proliferative vitreoretinopathy) were associated with several early apoptotic factors (caspase-8, caspase-9, and B-cell lymphoma 2 [Bcl-2]-associated death promoter [BAD]). Furthermore, both early apoptosis factors (caspase-8, Bcl-2, and p53) and signal-transduction proteins (ERK 1/2) were found to influence the postsurgery month 3 OCT characteristics. Conclusions: Signal-transduction proteins and early apoptosis proteins are associated with different clinical features and postsurgery outcomes.

Comparison of Guided and Unguided Ocriplasmin Injection for the Treatment of Vitreomacular Traction: A Preliminary Study.

This retrospective quality control study aimed at comparing resolution in patients treated with intravitreal ocriplasmin (IVO) using two injection techniques, classical injection procedure (unguided) and targeted injection using a surgical microscope with a 30-gauge 1-inch needle (guided) for the treatment of focal VMT without macular hole. The two groups presented a statistically significant difference in terms of resolution of VMT within the first month following treatment: 1/7 for the unguided group versus 6/7 for the guided group (p = 0.0291). The majority of the guided group presented an earlier resolution than the single resolved case in the unguided group. The results of this preliminary study indicate that the injection of ocriplasmin closer to the site of VMT results in the resolution in a higher number of cases and that this resolution occurs in a short time interval.

Retinal structural changes in a case of spontaneous resolution of vitreomacular traction syndrome: multimodal retinal imaging approach.

PURPOSE: Retinal structural changes in a case of spontaneous resolution of vitreomacular traction (VMT) syndrome were followed by means of multimodal retinal imaging approach. METHODS: Confocal scanning laser ophthalmoscopy (cSLO) including digital infrared and blue reflectance (BR) imaging and spectral-domain optical coherence tomography (SD-OCT) were performed in a young man with VMT syndrome. RESULTS: At the time of diagnosis, multimodal retinal imaging documented outer retina abnormalities linked to VMT. At 1 month follow-up visit, improvement of best-corrected visual acuity and resolution of metamorphopsia were accompanied by documentation of VMT resolution and outer retina restoration. CONCLUSIONS: Both cSLO and SD-OCT imaging, particularly BR and en face OCT adapted to the outer plexiform layer contour, allowed to depict outer retina changes in the course of VMT resolution. A strict correlation between topographic BR images and en face OCT scans was evident.

Reproducibility and repeatability of ganglion cell-inner plexiform layer thickness measurements in healthy subjects.

PURPOSE: To assess the reproducibility and repeatability of macular ganglion cell-inner plexiform layer (GC-IPL) thickness measurements in healthy subjects. PROCEDURES: In this observational study, 60 healthy eyes were subjected to macular GC-IPL thickness measurements by means of Cirrus™ high-definition optical coherence tomography (Cirrus version 6.0; Carl Zeiss Meditec, Dublin, Calif., USA) by two examiners in two sessions. Average, minimum and 6 sectoral GC-IPL thicknesses were measured. Inter- and intraobserver reproducibility was tested and analyzed by means of the concordance correlation coefficient (CCC). The repeatability of measurements was assessed by the coefficient of repeatability (CR). RESULTS: Mean age (±SD) was 29.63 (±5.1) years. The CRs for average GC-IPL thickness were 2.1 and 2.2 µm for the first and the second operator, respectively. Inter- and intraobserver CCCs ranged from 0.91 (95% CI: 0.89-0.93) to 0.98 (95% CI: 0.96-0.99) and from 0.92 (95% CI: 0.88-0.94) to 0.98 (95% CI: 0.97-0.99), respectively. CONCLUSIONS: GC-IPL thickness measurements in young healthy subjects showed excellent reproducibility and repeatability, especially for average and sectoral GC-IPL thickness measurements.

Reproducibility and repeatability of Cirrus™ HD-OCT peripapillary retinal nerve fibre layer thickness measurements in young normal subjects.

PURPOSE: To assess the reproducibility and repeatability of peripapillary retinal nerve fibre layer (RNFL) thickness measurements using a spectral-domain optical coherence tomography (SD-OCT) device in healthy subjects. METHODS: In this observational study, 68 young Caucasian healthy volunteers (68 eyes) were subjected to Cirrus™ high-definition (HD) OCT (Zeiss) peripapillary RNFL thickness measurements by two experienced examiners in two different sessions. Average, 4-quadrant and 12-clock-hour sector RNFL thicknesses were analysed. For each option, intra-observer, intrasession repeatability and interobserver, intersession reproducibility were tested. To assess the repeatability of measurements, the Bland and Altman plots were used and the coefficient of repeatability was calculated. Interobserver and intersession reproducibilities were analysed by means of concordance correlation coefficients (CCCs). RESULTS: The sample age ranged from 21 to 39 years (mean 29.09, standard deviation ±5.21). The average RNFL thickness ranged from 90.97 to 91.46 and from 91.34 to 91.78 µm, for the first and the second operator, respectively. The highest repeatability and reproducibility were obtained for average RNFL thickness with coefficients of repeatability of 5.30 and 6.05 µm for the first and the second operator, interoperator CCCs of 0.95 and 0.96 for the first and the second session, and intersession CCCs of 0.96 and 0.97 for the first and the second operator, respectively. CONCLUSIONS: Cirrus OCT peripapillary average RNFL thickness measurement in young healthy subjects showed high interoperator and intersession reproducibility. Intrasession repeatability as tested by coefficient of repeatability was next to the device resolution, with very similar results between the two operators. When analysing quadrant and clock hour sector RNFL thickness measurements, both repeatability and reproducibility tend to decrease.

The role of diagnostic imaging techniques in the management of retinal detachment due to macular hole in high myopia.

After preoperative assessment revealed anomalous posterior vitreous detachment, a 75-year-old woman affected with retinal detachment due to macular hole was scheduled to undergo the posterior episcleral buckling procedure. Preoperative microperimetry showed unstable eccentric fixation with a dense scotoma within the central 8 degrees. One month postoperatively, best-corrected visual acuity increased from 1.70 to 0.88 logarithm of the minimum angle of resolution. Ultrasonography and optical coherence tomography revealed the indentation of the posterior scleral profile due to the buckle. The retina appeared fully attached and a macular hole with flattened edges was still detectable. Microperimetry showed stable central fixation with recovery of retinal sensitivity within the central 2 degrees. Diagnostic imaging techniques guided the decision to use the posterior episcleral buckling procedure. Microperimetry was useful to explain vision improvement despite residual macular hole.